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Kumar R, Kumar A, Kumar S. Sepsis in liver failure patients: Diagnostic challenges and recent advancements. World J Crit Care Med 2025; 14:101587. [DOI: 10.5492/wjccm.v14.i2.101587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 01/19/2025] [Accepted: 02/12/2025] [Indexed: 02/27/2025] Open
Abstract
Acute liver failure (ALF) and acute-on-chronic LF (ACLF) are prevalent hepatic emergencies characterized by an increased susceptibility to bacterial infections (BI), despite significant systemic inflammation. Literature indicates that 30%–80% of ALF patients and 55%–81% of ACLF patients develop BI, attributed to immunological dysregulation. Bacterial sepsis in these patients is associated with adverse clinical outcomes, including prolonged hospitalization and increased mortality. Early detection of bacterial sepsis is critical; however, distinguishing between sterile systemic inflammation and sepsis poses a significant challenge due to the overlapping clinical presentations of LF and sepsis. Conventional sepsis biomarkers, such as procalcitonin and C-reactive protein, have shown limited utility in LF patients due to inconsistent results. In contrast, novel biomarkers like presepsin and sTREM-1 have demonstrated promising discriminatory performance in this population, pending further validation. Moreover, emerging research highlights the potential of machine learning-based approaches to enhance sepsis detection and characterization. Although preliminary findings are encouraging, further studies are necessary to validate these results across diverse patient cohorts, including those with LF. This article provides a comprehensive review of the magnitude, impact, and diagnostic challenges associated with BI in LF patients, focusing on novel advancements in early sepsis detection and characterization.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Abhishek Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Sudhir Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
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Lee S, Arefaine B, Begum N, Stamouli M, Witherden E, Mohamad M, Harzandi A, Zamalloa A, Cai H, Williams R, Curtis MA, Edwards LA, Chokshi S, Mardinoglu A, Proctor G, Moyes DL, McPhail MJ, Shawcross DL, Uhlen M, Shoaie S, Patel VC. Oral-gut microbiome interactions in advanced cirrhosis: characterisation of pathogenic enterotypes and salivatypes, virulence factors and antimicrobial resistance. J Hepatol 2025; 82:622-633. [PMID: 39447963 DOI: 10.1016/j.jhep.2024.09.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 09/11/2024] [Accepted: 09/30/2024] [Indexed: 10/26/2024]
Abstract
BACKGROUND & AIMS Cirrhosis complications are often triggered by bacterial infections with multidrug-resistant organisms. Alterations in the gut and oral microbiome in decompensated cirrhosis (DC) influence clinical outcomes. We interrogated: (i) gut and oral microbiome community structures, (ii) virulence factors (VFs) and antimicrobial resistance genes (ARGs) and (iii) oral-gut microbial overlap in patients with differing cirrhosis severity. METHODS Fifteen healthy controls (HCs), as well as 26 patients with stable cirrhosis (SC), 46 with DC, 14 with acute-on-chronic liver failure (ACLF) and 14 with severe infection without cirrhosis participated. Metagenomic sequencing was undertaken on paired saliva and faecal samples. 'Salivatypes' and 'enterotypes' based on genera clustering were assessed against cirrhosis severity and clinical parameters. VFs and ARGs were evaluated in oral and gut niches, and distinct resistotypes identified. RESULTS Salivatypes and enterotypes revealed a greater proportion of pathobionts with concomitant reduction in autochthonous genera with increasing cirrhosis severity and hyperammonaemia. Increasing overlap between oral and gut microbiome communities was observed in DC and ACLF vs. SC and HCs, independent of antimicrobial, beta-blocker and gastric acid-suppressing therapies. Two distinct gut microbiome clusters harboured genes encoding for the PTS (phosphoenolpyruvate:sugar phosphotransferase system) and other VFs in DC and ACLF. Substantial ARGs (oral: 1,218 and gut: 672) were detected (575 common to both sites). The cirrhosis resistome was distinct, with three oral and four gut resistotypes identified, respectively. CONCLUSIONS The degree of oral-gut microbial community overlap, frequency of VFs and ARGs all increase significantly with cirrhosis severity, with progressive dominance of pathobionts and loss of commensals. Despite similar antimicrobial exposure, patients with DC and ACLF have reduced microbial richness compared to patients with severe infection without cirrhosis, supporting the additive pathobiological effect of cirrhosis. IMPACT AND IMPLICATIONS This research underscores the crucial role of microbiome alterations in the progression of cirrhosis in an era of escalating multidrug resistant infections, highlighting the association and potential impact of increased oral-gut microbial overlap, virulence factors, and antimicrobial resistance genes on clinical outcomes. These findings are particularly significant for patients with decompensated cirrhosis and acute-on-chronic liver failure, as they reveal the intricate relationship between microbiome alterations and cirrhosis complications. This is relevant in the context of multidrug-resistant organisms and reduced oral-gut microbial diversity that exacerbate cirrhosis severity, drive hepatic decompensation and complicate treatment. For practical applications, these insights could guide the development of targeted microbiome-based therapeutics and personalised antimicrobial regimens for patients with cirrhosis to mitigate infectious complications and improve clinical outcomes.
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Affiliation(s)
- Sunjae Lee
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom; School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea
| | - Bethlehem Arefaine
- Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
| | - Neelu Begum
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom
| | - Marilena Stamouli
- Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
| | - Elizabeth Witherden
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom
| | - Merianne Mohamad
- Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
| | - Azadeh Harzandi
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom
| | - Ane Zamalloa
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Haizhuang Cai
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom
| | - Roger Williams
- Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
| | - Michael A Curtis
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom; Dental Clinical Academic Group, King's Health Partners, United Kingdom
| | - Lindsey A Edwards
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom
| | - Shilpa Chokshi
- Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
| | - Adil Mardinoglu
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-171 21, Sweden
| | - Gordon Proctor
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom; Dental Clinical Academic Group, King's Health Partners, United Kingdom
| | - David L Moyes
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom
| | - Mark J McPhail
- Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom; Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Debbie L Shawcross
- Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom; Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom
| | - Mathias Uhlen
- Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-171 21, Sweden
| | - Saeed Shoaie
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, United Kingdom; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-171 21, Sweden.
| | - Vishal C Patel
- Roger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom; Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom.
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Goran LG, Liţă (Cofaru) FA, Fierbinţeanu-Braticevici C. Acute-on-Chronic Liver Failure: Steps Towards Consensus. Diagnostics (Basel) 2025; 15:751. [PMID: 40150093 PMCID: PMC11941433 DOI: 10.3390/diagnostics15060751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2025] [Revised: 03/09/2025] [Accepted: 03/14/2025] [Indexed: 03/29/2025] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by organ failure and high short-term mortality. Since its first definition in 2013, many international organizations have defined this syndrome and, till now, there has been no agreement regarding definitions and diagnostic criteria. Although the precise mechanism of ACLF is unknown, precipitant factors and the systemic inflammation response play a major role. Specific management of this high-mortality syndrome is still under development, but a general consensus in the diagnosis and management of ACLF is needed.
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Affiliation(s)
- Loredana Gabriela Goran
- Emergency University Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (F.A.L.); (C.F.-B.)
- Internal Medicine II and Gastroenterology Department, University Emergency Hospital Bucharest, 050098 Bucharest, Romania
| | - Florina Alexandra Liţă (Cofaru)
- Emergency University Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (F.A.L.); (C.F.-B.)
- Emergency Department, University Emergency Hospital Bucharest, 050098 Bucharest, Romania
| | - Carmen Fierbinţeanu-Braticevici
- Emergency University Hospital Bucharest, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania; (F.A.L.); (C.F.-B.)
- Internal Medicine II and Gastroenterology Department, University Emergency Hospital Bucharest, 050098 Bucharest, Romania
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Pohl J, Aretakis D, Tacke F, Engelmann C, Sigal M. Role of Intestinal Barrier Disruption to Acute-on-Chronic Liver Failure. Semin Liver Dis 2025. [PMID: 40081417 DOI: 10.1055/a-2516-2361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/16/2025]
Abstract
Acute-on-chronic liver failure (ACLF) is a severe condition in patients with decompensated liver cirrhosis, marked by high short-term mortality. Recent experimental and clinical evidence has linked intestinal dysfunction to both the initiation of ACLF as well as disease outcome. This review discusses the significant role of the gut-liver axis in ACLF pathogenesis, highlighting recent advances. Gut mucosal barrier disruption, gut dysbiosis, and bacterial translocation emerge as key factors contributing to systemic inflammation in ACLF. Different approaches of therapeutically targeting the gut-liver axis via farnesoid X receptor agonists, nonselective beta receptor blockers, antibiotics, and probiotics are discussed as potential strategies mitigating ACLF progression. The importance of understanding the distinct pathophysiology of ACLF compared with other stages of liver cirrhosis is highlighted. In conclusion, research findings suggest that disruption of intestinal integrity may be an integral component of ACLF pathogenesis, paving the way for novel diagnostic and therapeutic approaches to manage this syndrome more effectively.
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Affiliation(s)
- Julian Pohl
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Dimitrios Aretakis
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Cornelius Engelmann
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
- Institute for Liver and Digestive Health, University College London, London, United Kingdom
| | - Michael Sigal
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany
- Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
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Yang X, Li J, Yang Y, Zhang L, Dan X, Cai D, Zhou Z, Li H, Wang X, Zhong S. Early prediction of invasive fungal infection risk in acute-on-chronic liver failure: a prediction model based on admission indicators. BMC Microbiol 2025; 25:131. [PMID: 40069589 PMCID: PMC11900632 DOI: 10.1186/s12866-025-03819-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Accepted: 02/10/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is a severe clinical syndrome, and the incidence of invasive fungal infection (IFI) among hospitalized patients with ACLF is steadily increasing. The aim of this study is to develop a diagnostic nomogram to assist in the identification of IFI in these patients. METHODS A retrospective study included 705 patients from January 1, 2019, to October 31, 2023, randomly divided into training (n = 493) and validation (n = 212) cohorts. The diagnosis of IFI includes proven diagnosis and probable diagnosis. Kaplan analysis was performed to analyze the survival prognosis of ACLF patients with and without IFI. A nomogram was developed based on a logistic regression model derived through least absolute shrinkage and selection operator (LASSO) regression. The discrimination, accuracy, and clinical utility of the model were assessed using receiver operating characteristic curves, Hosmer-Lemeshow tests, calibration plots, and decision curve analysis. RESULTS Kaplan-Meier survival analysis confirmed that the median survival time of ACLF patients with IFI was significantly lower (by 68 days) than that of ACLF patients without IFI, and there were significant differences in the 90-day, 180-day, and 360-day survival rates between the two groups (P < 0.05). Based on LASSO regression, the following factors were identified as significant risk factors for predicting IFI: aminotransferase levels, prothrombin activity, hemoglobin, neutrophil-to-lymphocyte ratio, and serum total bilirubin. A nomogram was constructed incorporating these variables. The nomogram demonstrated good discriminative ability, with an area under the receiver operating characteristic curve (AUC) of 0.78 (95% confidence interval [CI]: 0.72-0.84) in the training cohort and 0.79 (95% CI: 0.70-0.87) in the validation cohort. Decision curve analysis further validated the clinical applicability of the nomogram. CONCLUSION ACLF patients with IFI have lower survival time than those without IFI. A nomogram was developed and validated to assist clinicians in the early prediction of IFI in hospitalized patients with ACLF. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Xu Yang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, No.288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China
| | - Jie Li
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, No.288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China
| | - Yanli Yang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, No.288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China
| | - Li Zhang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, No.288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China
| | - Xuelian Dan
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, No.288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China
| | - Dachuan Cai
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, No.288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China
| | - Zhi Zhou
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, No.288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China
| | - Hu Li
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, No.288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China
| | - Xiaohao Wang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, No.288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China.
| | - Shan Zhong
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University, No.288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China.
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Morrison MA, Artru F, Trovato FM, Triantafyllou E, McPhail MJ. Potential therapies for acute-on-chronic liver failure. Liver Int 2025; 45:e15545. [PMID: 36800487 DOI: 10.1111/liv.15545] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 01/16/2023] [Accepted: 02/15/2023] [Indexed: 02/19/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is a syndrome that develops in approximately 30% of patients hospitalised with cirrhosis and is characterised by an acute decompensation of liver function associated with extra-hepatic organ failures and a high short-term mortality. At present, no specific therapies are available for ACLF, and current management is limited to treatment of the precipitating event and organ support. Given the high prevalence and high mortality of this severe liver disease, there is an urgent need for targeted treatments. There is increasing evidence of the important role played by systemic inflammation and immune dysfunction in the pathophysiology of ACLF and a better understanding of these immune processes is resulting in new therapeutic targets. The aim of this review is to present an overview of ongoing studies of potentially promising therapies and how they could be utilised in the management of ACLF.
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Affiliation(s)
- Maura A Morrison
- Institute of Liver Studies, King's College Hospital, London, UK
- Department of Inflammation Biology, School of Immunology and Microbial Sciences, King's College London, London, UK
| | - Florent Artru
- Institute of Liver Studies, King's College Hospital, London, UK
- Department of Inflammation Biology, School of Immunology and Microbial Sciences, King's College London, London, UK
| | - Francesca M Trovato
- Institute of Liver Studies, King's College Hospital, London, UK
- Department of Inflammation Biology, School of Immunology and Microbial Sciences, King's College London, London, UK
| | - Evangelos Triantafyllou
- Section of Hepatology and Gastroenterology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Mark J McPhail
- Institute of Liver Studies, King's College Hospital, London, UK
- Department of Inflammation Biology, School of Immunology and Microbial Sciences, King's College London, London, UK
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Piano S, Mahmud N, Caraceni P, Tonon M, Mookerjee RP. Mechanisms and treatment approaches for ACLF. Liver Int 2025; 45:e15733. [PMID: 37715608 DOI: 10.1111/liv.15733] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 08/03/2023] [Accepted: 09/02/2023] [Indexed: 09/17/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome characterized by decompensation of cirrhosis, severe systemic inflammation and organ failures. ACLF is frequently triggered by intra- and/or extrahepatic insults, such as bacterial infections, alcohol-related hepatitis or flares of hepatic viruses. The imbalance between systemic inflammation and immune tolerance causes organ failures through the following mechanisms: (i) direct damage of immune cells/mediators; (ii) worsening of circulatory dysfunction resulting in organ hypoperfusion and (iii) metabolic alterations with prioritization of energetic substrates for inflammation and peripheral organ 'energetic crisis'. Currently, the management of ACLF includes the support of organ failures, the identification and treatment of precipitating factors and expedited assessment for liver transplantation (LT). Early LT should be considered in patients with ACLF grade 3, who are unlikely to recover with the available treatments and have a mortality rate > 70% at 28 days. However, the selection of transplant candidates and their prioritization on the LT waiting list need standardization. Future challenges in the ACLF field include a better understanding of pathophysiological mechanisms leading to inflammation and organ failures, the development of specific treatments for the disease and personalized treatment approaches. Herein, we reviewed the current knowledge and future perspectives on mechanisms and treatment of ACLF.
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Affiliation(s)
- Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine - DIMED, University and Hospital of Padova, Padova, Italy
| | - Nadim Mahmud
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- Leonard Davis Institute of Health Economics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Gastroenterology Section, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Unit of Semeiotics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Marta Tonon
- Unit of Internal Medicine and Hepatology, Department of Medicine - DIMED, University and Hospital of Padova, Padova, Italy
| | - Rajeshwar Prosad Mookerjee
- Institute for Liver and Digestive Health, University College London, London, UK
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus C, Denmark
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8
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Patel P, Lodh A, Beasley TM, Gupta U, Forrister N, Hegazy Y, Evers C, Xie S, Shoreibah M. Optimizing treatment outcomes in acute-on-chronic liver failure: The role of T2 candida panel in detecting invasive candidiasis. Am J Med Sci 2025; 369:366-372. [PMID: 39510501 DOI: 10.1016/j.amjms.2024.10.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 10/22/2024] [Accepted: 10/25/2024] [Indexed: 11/15/2024]
Abstract
INTRODUCTION Acute-on-Chronic Liver Failure(ACLF) is a syndrome characterized by organ dysfunction and high mortality in cirrhotic patients. ACLF has multiple triggers but those precipitated by fungal infection have higher mortality. Early detection and treatment of candidemia have shown mortality benefits in ACLF. The sensitivity of blood cultures ranged from 21 % - 71 %. Given the increase in mortality, it is vital to have a quick yet reliable diagnostic test for the detection of candida. This study examines the risk of developing ACLF and its impact on survival in hospitalized cirrhotic patients with invasive fungal infection via a positive T2 Candida Panel. We also examine the effects of earlier treatment on mortality in those with a positive T2 Candida Panel. METHODS We performed a retrospective study and included cirrhotic patients admitted from 2017 to 2021. Data collected includes baseline characteristics, labs, progression to ACLF, and mortality outcomes. The stages of ACLF were determined through the use of the CLIF-Consortium ACLF score. RESULTS Of the 489 patients sampled, 95 patients developed ACLF during the time of the T2 panel collection, of which 60 (63.2 %) (p ≤ 0.001) patients had a positive T2 Candida Panel. The data also demonstrates that patients who had earlier antifungal initiation had a decrease in mortality (6.15 ± 5.23 versus 13.53 ± 11.42)(p ≤ 001). CONCLUSION Our study shows that a positive T2 Panel leads to more frequent progression of ACLF and worsening survival outcomes. This study shows that earlier treatment of candidiasis via the T2 Panel leads to mortality benefits.
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Affiliation(s)
- P Patel
- University of Alabama at Birmingham, Birmingham, AL, USA; Princeton Baptist Medical Center, Birmingham, AL, USA.
| | - A Lodh
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - T M Beasley
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - U Gupta
- University of New Mexico, Albuquerque, NM, USA
| | - N Forrister
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - Y Hegazy
- University of Mississippi, Jackson, MS, USA
| | - C Evers
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - S Xie
- University of Alabama at Birmingham, Birmingham, AL, USA
| | - M Shoreibah
- University of Alabama at Birmingham, Birmingham, AL, USA
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9
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Hernaez R, Li H, Moreau R, Coenraad MJ. Definition, diagnosis and epidemiology of acute-on-chronic liver failure. Liver Int 2025; 45:e15670. [PMID: 37424175 DOI: 10.1111/liv.15670] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 06/14/2023] [Accepted: 06/27/2023] [Indexed: 07/11/2023]
Abstract
This narrative review addresses the definition of acute-on-chronic liver failure, a condition associated with high short-term mortality in patients with chronic liver disease and/or cirrhosis. We provide two major points of view: the East and the West perspective. Both definitions vary regarding the underlying patient population and organ failure(s) definition. Nevertheless, all the definitions have their clinical utility: from the core concept of having the "liver" as a conditio sine qua non, the syndrome cannot exist (Asian Pacific Association for the Study of the Liver); a data-driven, robust definition (European Association for the Study of the Liver); a bedside tool that can quickly identify patients at high risk of dying (North American Consortium for the Study of End-stage Liver Disease [NACSELD]). In each section, we provide the overall definitions, the criteria of organ failure(s), and some epidemiological data illustrating how these apply in each area of the world.
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Affiliation(s)
- Ruben Hernaez
- Section of Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center, TX Center, Houston, Texas, USA
- VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center, Houston, Texas, USA
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Hai Li
- Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Richard Moreau
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, France
- INSERM, Université de Paris Cité, Centre de Recherche sur l'Inflammation (CRI), Service d'Hépatologie, Paris, France
- Assistance Publique-Hôpitaux de Paris (AP-HP), and Hôpital Beaujon, Clichy, France
| | - Minneke J Coenraad
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands
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Karvellas CJ, Gustot T, Fernandez J. Management of the acute on chronic liver failure in the intensive care unit. Liver Int 2025; 45:e15659. [PMID: 37365997 DOI: 10.1111/liv.15659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2023] [Revised: 06/01/2023] [Accepted: 06/15/2023] [Indexed: 06/28/2023]
Abstract
Acute on chronic liver failure (ACLF) reflects the development of organ failure(s) in a patient with cirrhosis and is associated with high short-term mortality. Given that ACLF has many different 'phenotypes', medical management needs to take into account the relationship between precipitating insult, organ systems involved and underlying physiology of chronic liver disease/cirrhosis. The goals of intensive care management of patients suffering ACLF are to rapidly recognize and treat inciting events (e.g. infection, severe alcoholic hepatitis and bleeding) and to aggressively support failing organ systems to ensure that patients may successfully undergo liver transplantation or recovery. Management of these patients is complex since they are prone to develop new organ failures and infectious or bleeding complications. ICU therapy parallels that applied in the general ICU population in some complications but differs in others. Given that liver transplantation in ACLF is an emerging and evolving field, multidisciplinary teams with expertise in critical care and transplant medicine best accomplish management of the critically ill ACLF patient. The focus of this review is to identify the common complications of ACLF and to describe the proper management in critically ill patients awaiting liver transplantation in our centres, including organ support, prognostic assessment and how to assess when recovery is unlikely.
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Affiliation(s)
- Constantine J Karvellas
- Department of Critical Care Medicine, University of Alberta, Edmonton, Canada
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada
| | - Thierry Gustot
- Department of Gastroenterology, Hepato-Pancreatology and Digestive Oncology, H.U.B., CUB Hôpital Erasme, Brussels, Belgium
| | - Javier Fernandez
- Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS and CIBERehd, Barcelona, Spain
- EF CLIF, EASL-CLIF Consortium, Barcelona, Spain
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11
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Trebicka J, Aguilar F, Queiroz Farias A, Lozano JJ, Sánchez-Garrido C, Usón-Raposo E, de la Peña-Ramirez C, Sidorova J, Curto-Vilalta A, Sierra-Casas P, Momoyo Zitelli P, Papp M, Pereira G, Caraceni P, Goncalves LL, Alessandria C, Torre A, Laleman W, Gadano A, Piano S, Mattos AZ, Gu W, Brol MJ, Schierwagen R, Uschner FE, Fischer J, Mendes LSC, Vargas V, Alvares-da-Silva MR, Mookerjee R, Bittencourt PL, Benitez C, Albillos A, Couto C, Mendizabal M, Bañares R, Toledo CL, Mazo DF, Janicko M, Castillo-Barradas M, Padilla Machaca PM, Gatti P, Miranda AZL, Malé-Velázquez R, Zipprich A, Castro-Lyra A, Gustot T, Bernal W, Gerbes AL, Jalan R, Fernández J, Angeli P, Carrilho FJ, Claria J, Moreau R, Arroyo V. Gene score to quantify systemic inflammation in patients with acutely decompensated cirrhosis. Gut 2025:gutjnl-2024-333876. [PMID: 40011033 DOI: 10.1136/gutjnl-2024-333876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Accepted: 02/10/2025] [Indexed: 02/28/2025]
Abstract
BACKGROUND AND AIMS Quantifying systemic inflammation (SI) in acutely decompensated cirrhosis (ADC) is of major importance because SI is a driver of the most severe forms of ADC, including acute-on-chronic liver failure (ACLF). Blood biomarkers of SI already evaluated in ADC failed to appropriately assess SI in ADC. We aimed to investigate whether gene expression related to circulating immune cells could quantify SI in ADC. METHODS Standard biomarkers (white cell count, C reactive protein, cytokines) and genome-wide RNA expression (RNA-sequencing) were obtained in blood from 700 patients with ADC at the time of their hospital admission. A composite score based on standard biomarkers of SI (Chronic Liver Failure-Standard Biomarkers Composite (CLIF-SBC) score) and a gene score (CLIF-Systemic Inflammation Gene (SIG) score) composed of the 28 top differentially expressed immune cell-related genes in the comparison between high-severity and low-severity clinical phenotypes were computed. Among the 700 patients, the CLIF-SIG score was repeated once during follow-up in 375 patients, and 3 times or more in 46 patients. RESULTS The CLIF-SIG score was more accurate in reflecting clinical severity induced by SI than the CLIF-SBC score (area under the curve 0.803 vs 0.658). A CLIF-SIG score of 0.386 (Youden Index) was the best cut-off level discriminating patients with poor outcomes from the others, in all clinical scenarios. Sequential measurement of the CLIF-SIG score showed that 78% of patients were admitted at the peak or descending part of the SI-wave. ACLF developed during hospitalisation in 80% of patients with a CLIF-SIG score >0.386 on admission. CONCLUSIONS In patients with ADC, the CLIF-SIG score is an accurate estimator of SI, clinical course severity and prognosis.
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Affiliation(s)
- Jonel Trebicka
- Department of Internal Medicine B, University of Münster, Munster, Germany
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
| | - Ferran Aguilar
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
- University of Barcelona (UB), Barcelona, Spain
| | - Alberto Queiroz Farias
- Department of Gastroenterology, Hospital das Clinicas, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Juan-José Lozano
- Liver Unit, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | | | - Eva Usón-Raposo
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
| | | | - Julia Sidorova
- Liver Unit, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Anna Curto-Vilalta
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
| | - Patricia Sierra-Casas
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
| | - Patricia Momoyo Zitelli
- Department of Gastroenterology, Hospital das Clinicas, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Maria Papp
- Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Gustavo Pereira
- Gastroenterology and Hepatology Unit, Bonsucesso Federal Hospital, Rio de Janeiro, Brazil
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Luciana L Goncalves
- Gastroenterology and Hepatology Unit, Cassiano Antonio Moraes University Hospital, Vitoria, Brazil
| | - Carlo Alessandria
- Azienda Ospedaliero Universitaria Citta della Salute e della Scienza di Torino, Torino, Italy
| | - Aldo Torre
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Wim Laleman
- Department of Internal Medicine B, University of Münster, Munster, Germany
- Division of Liver and Biliopanreatic Disorders, KU Leuven, University of Leuven, Leuven, Belgium
| | - Adrián Gadano
- Liver Unit and Department of Research, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Salvatore Piano
- Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Angelo Z Mattos
- Gastroenterology and Hepatology Unit, Federal University of Health Sciences, Porto Alegre, Brazil
| | - Wenyi Gu
- Department of Internal Medicine B, University of Münster, Munster, Germany
- Hospital of the Goethe University Frankfurt, Frankfurt am Main, Germany
| | | | - Robert Schierwagen
- Department of Internal Medicine B, University of Münster, Munster, Germany
| | - Frank Erhard Uschner
- Department of Internal Medicine B, University of Münster, Munster, Germany
- Hospital of the Goethe University Frankfurt, Frankfurt am Main, Germany
| | - Julia Fischer
- Department of Internal Medicine B, University of Münster, Munster, Germany
| | | | - Victor Vargas
- Liver Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | | | - Raj Mookerjee
- Institute of Liver and Digestive Health, University College London Medical School, London, UK
| | | | - Carlos Benitez
- Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | | | - Cláudia Couto
- Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Manuel Mendizabal
- Hepatology and Liver Unit, Hospital Universitario Austral, Pilar, Argentina
| | - Rafael Bañares
- Gastroenterology, IRYCIS, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Claudio L Toledo
- Gastroenterology Unit, Universidad Austral de Chile, Valdivia, Chile
| | - Daniel F Mazo
- Gastroenterology Unit, State University of Campinas, Campinas, Brazil
| | - Martin Janicko
- Pavol Jozef Stafarik University in Kosice Faculty of Medicine, Kosice, Slovakia
| | | | | | - Pietro Gatti
- Internal Medicine PO Ostuni, ASL Brindisi, Brindisi, Italy
| | | | | | - Alexander Zipprich
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
| | - André Castro-Lyra
- Hospital Universitario Professor Edgard Santos, Salvador, Brazil
- Hospital Sao Rafael, Salvador, Brazil
| | | | - William Bernal
- Institute of Liver Studies, King's College Hospital, London, UK
| | | | - Rajiv Jalan
- Institute of Liver and Digestive Health, University College London Medical School, London, UK
| | - Javier Fernández
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
| | - Paolo Angeli
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
- Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy
| | - Flair Jose Carrilho
- Gastroenterology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Joan Claria
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
- Department of Biochemistry/Molecular Genetics, Hospital Clinic/University of Barcelona, Barcelona, Spain
| | - Richard Moreau
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
- INSERM, Université Paris Cité, Centre de Recherche sur l'Inflammation (CRI), Paris, France
- Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Beaujon, Service d'Hépatologie, Clichy, France
| | - Vicente Arroyo
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
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12
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Chen J, Liu X, Guan C, Peng Y, Li C, Yan L, Ning P, Hu J, Su H. Sterile systemic inflammation reaction associated with 90-day mortality in patients with HBV-related acute-on-chronic liver failure. Eur J Gastroenterol Hepatol 2025:00042737-990000000-00483. [PMID: 39976056 DOI: 10.1097/meg.0000000000002937] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) represents the terminal and most lethal phase of acute decompensated cirrhosis. Systemic inflammation plays a critical role in the pathogenesis of ACLF. Systemic inflammation reaction syndrome (SIRS) is a marker of ongoing inflammation. Therefore, we aim to evaluate the relationship of sterile SIRS with hepatitis B virus (HBV)-related ACLF (HBV-ACLF). METHODS HBV-ACLF patients with sterile SIRS who were hospitalized between December 2016 and December 2018 were retrospectively analyzed. All patients were followed up until 90 days. Risk factors associated with 90-day mortality and sterile SIRS development were assessed. RESULTS Among 151 HBV-ACLF patients without infection, 37 patients (24.5%) presented with or developed sterile SIRS. During the 90-day follow-up, 23 of the 37 patients with sterile SIRS died (62.2%), compared to 40 patients without sterile SIRS (35.1%, P = 0.004). Univariate analysis showed that age, total bilirubin (TBIL), international normalized ratio, ammonia, presence of sterile SIRS, model for end-stage liver disease score, presence of complications, and organ failures were associated with 90-day mortality. In multivariate analyses, the presence of sterile SIRS was an independent risk factor for 90-day mortality. Among SIRS components, heart rate (HR) was the most frequently met criterion (56 patients, 37.09%). Patients who met the HR or temperature criterion had lower 90-day survival rate than those who did not (46.4 vs 65.3%, P = 0.020; 16.7 vs 60.0%, P = 0.020). CONCLUSION The presence of sterile SIRS in HBV-ACLF patients was closely associated with prognosis.
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Affiliation(s)
- Jing Chen
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
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13
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McGettigan B, Hernandez-Tejero M, Malhi H, Shah V. Immune Dysfunction and Infection Risk in Advanced Liver Disease. Gastroenterology 2025:S0016-5085(24)05694-4. [PMID: 39927926 DOI: 10.1053/j.gastro.2024.08.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 08/21/2024] [Accepted: 08/22/2024] [Indexed: 02/11/2025]
Abstract
The risk of microbial infections is increased in cirrhosis and other forms of advanced liver disease such as alcohol-associated hepatitis. Such infections may precipitate new or further decompensation and death, especially in patients with clinical features of acute-on-chronic liver failure. The severe immune dysfunction or "immune paralysis" caused by advanced liver disease is associated with high short-term mortality. However, the pathogenic mechanisms underlying immune dysfunction and immunodeficiency are incompletely understood. Evidence to date suggests a complex, dynamic process that perturbs the physiological roles of the liver as a master regulator of systemic immunity and protector against noxious effects of exogenous molecules in the portal vein flowing from the gut. Thus, in cirrhosis and severe alcohol-associated hepatitis, the ability of hepatocytes and intrahepatic immune cells to balance normal context-dependent dichotomous responses of tolerance vs immune activation is lost. Contributing factors include loss of the gut barrier with translocation of microbial products through the portal vein, culminating in development of functional defects in innate and adaptive immune cells, and generation of immune-regulatory myeloid cells that permit microbial colonization and infection. This review addresses key evidence supporting the paradigm of immune dysfunction as a risk for microbial infections and identifies potential therapeutic targets for intervention. The primary focus is on cirrhosis-associated immune dysfunction and alcohol-associated liver disease, because the bulk of available data are from these 2 conditions.
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Affiliation(s)
- Brett McGettigan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Maria Hernandez-Tejero
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Harmeet Malhi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
| | - Vijay Shah
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
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14
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Feio-Azevedo R, Boesch M, Radenkovic S, van Melkebeke L, Smets L, Wallays M, Boeckx B, Philips G, Prata de Oliveira J, Ghorbani M, Laleman W, Meersseman P, Wilmer A, Cassiman D, van Malenstein H, Triantafyllou E, Sánchez C, Aguilar F, Nevens F, Verbeek J, Moreau R, Arroyo V, Denadai Souza A, Clària J, Lambrechts D, Ghesquière B, Korf H, van der Merwe S. Distinct immunometabolic signatures in circulating immune cells define disease outcome in acute-on-chronic liver failure. Hepatology 2025; 81:509-522. [PMID: 38761406 PMCID: PMC11737128 DOI: 10.1097/hep.0000000000000907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 04/07/2024] [Indexed: 05/20/2024]
Abstract
BACKGROUND AND AIMS Acute-on-chronic liver failure (ACLF) is a complication of cirrhosis characterized by multiple organ failure and high short-term mortality. The pathophysiology of ACLF involves elevated systemic inflammation leading to organ failure, along with immune dysfunction that heightens susceptibility to bacterial infections. However, it is unclear how these aspects are associated with recovery and nonrecovery in ACLF. APPROACH AND RESULTS Here, we mapped the single-cell transcriptome of circulating immune cells from patients with ACLF and acute decompensated (AD) cirrhosis and healthy individuals. We further interrogate how these findings, as well as immunometabolic and functional profiles, associate with ACLF-recovery (ACLF-R) or nonrecovery (ACLF-NR). Our analysis unveiled 2 distinct states of classical monocytes (cMons). Hereto, ACLF-R cMons were characterized by transcripts associated with immune and stress tolerance, including anti-inflammatory genes such as RETN and LGALS1 . Additional metabolomic and functional validation experiments implicated an elevated oxidative phosphorylation metabolic program as well as an impaired ACLF-R cMon functionality. Interestingly, we observed a common stress-induced tolerant state, oxidative phosphorylation program, and blunted activation among lymphoid populations in patients with ACLF-R. Conversely, ACLF-NR cMon featured elevated expression of inflammatory and stress response genes such as VIM , LGALS2 , and TREM1 , along with blunted metabolic activity and increased functionality. CONCLUSIONS This study identifies distinct immunometabolic cellular states that contribute to disease outcomes in patients with ACLF. Our findings provide valuable insights into the pathogenesis of ACLF, shedding light on factors driving either recovery or nonrecovery phenotypes, which may be harnessed as potential therapeutic targets in the future.
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Affiliation(s)
- Rita Feio-Azevedo
- Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium
| | - Markus Boesch
- Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium
| | - Silvia Radenkovic
- Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium
- Metabolomics Expertise Center, Center for Cancer Biology, VIB Center for Cancer Biology, Leuven, Belgium
- Department of Oncology, Metabolomics Expertise Center, KU Leuven, Leuven, Belgium
- Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA
| | - Lukas van Melkebeke
- Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium
- Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium
| | - Lena Smets
- Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium
| | - Marie Wallays
- Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium
| | - Bram Boeckx
- Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium
- VIB Center for Cancer Biology, Leuven, Belgium
| | - Gino Philips
- Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium
- VIB Center for Cancer Biology, Leuven, Belgium
| | - Janaíne Prata de Oliveira
- Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Mohammad Ghorbani
- Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium
| | - Wim Laleman
- Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium
- Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium
| | | | - Alexander Wilmer
- Department of Internal Medicine, UZ Leuven, KU Leuven, Leuven, Belgium
| | - David Cassiman
- Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium
- Metabolomics Expertise Center, Center for Cancer Biology, VIB Center for Cancer Biology, Leuven, Belgium
- Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium
| | - Hannah van Malenstein
- Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium
- Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium
| | - Evangelos Triantafyllou
- Section of Hepatology and Gastroenterology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Cristina Sánchez
- European Foundation for the Study of Chronic Liver Failure, EF-CLIF, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain
| | - Ferran Aguilar
- European Foundation for the Study of Chronic Liver Failure, EF-CLIF, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain
| | - Frederik Nevens
- Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium
- Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium
| | - Jef Verbeek
- Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium
- Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium
| | - Richard Moreau
- European Foundation for the Study of Chronic Liver Failure, EF-CLIF, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain
- Centre de Recherche sur l’Inflammation (CRI) UMRS1149, Université de Paris Cité, Service d’Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France
| | - Vicente Arroyo
- European Foundation for the Study of Chronic Liver Failure, EF-CLIF, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain
| | | | - Joan Clària
- European Foundation for the Study of Chronic Liver Failure, EF-CLIF, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain
- Hospital Clínic-IDIBAPS, CIBERehd, Universitat de Barcelona, Barcelona, Spain
| | - Diether Lambrechts
- Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium
- VIB Center for Cancer Biology, Leuven, Belgium
| | - Bart Ghesquière
- Metabolomics Expertise Center, Center for Cancer Biology, VIB Center for Cancer Biology, Leuven, Belgium
- Department of Oncology, Metabolomics Expertise Center, KU Leuven, Leuven, Belgium
| | - Hannelie Korf
- Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium
| | - Schalk van der Merwe
- Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium
- Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium
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15
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Epelbaum O, de Moraes AG, Olson JC, Lionakis MS. Invasive fungal infections in patients with liver disease: immunological and clinical considerations for the intensive care unit. Intensive Care Med 2025; 51:364-377. [PMID: 39961846 PMCID: PMC11903580 DOI: 10.1007/s00134-025-07797-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 01/10/2025] [Indexed: 03/14/2025]
Abstract
Patients with liver disease in the intensive care unit (ICU) face a unique susceptibility to infection due to the complex immune dysfunction resulting from hepatic failure. Bacterial infections are commonly present in these patients upon arrival to the hospital, often being the primary reason for ICU admission. In contrast, invasive fungal infections (IFIs) afflict a smaller percentage of patients and are usually discovered in the course of the ICU stay. IFI diagnosis in the ICU, particularly in patients with liver disease, is often delayed or overlooked, contributing to the extremely high ICU mortality associated with IFI in these patients despite the availability of effective (and largely safe) antifungal therapy. Thus, to improve outcomes, it is crucial for intensive care clinicians to be vigilant for IFIs in patients with liver disease. This review aims to contribute to the intensive care literature in this regard. We begin with an overview of normal antifungal immunity followed by a summary of how it may become compromised in the setting of hepatic dysfunction. Next, a general discussion of IFIs in liver disease is presented and then the three most relevant fungal pathogens, namely Candida, Aspergillus, and Cryptococcus, are individually examined. This review concludes by highlighting key knowledge and practice gaps that require attention by the scientific and clinical communities in the coming years.
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Affiliation(s)
- Oleg Epelbaum
- Division of Pulmonary, Critical Care, and Sleep Medicine, Westchester Medical Center, Valhalla, NY, USA.
| | - Alice Gallo de Moraes
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic Rochester, Rochester, MN, USA
| | - Jody C Olson
- Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, MN, USA
| | - Michail S Lionakis
- Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
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Choudhury A, Kulkarni AV, Arora V, Soin AS, Dokmeci AK, Chowdhury A, Koshy A, Duseja A, Kumar A, Mishra AK, Patwa AK, Sood A, Roy A, Shukla A, Chan A, Krag A, Mukund A, Mandot A, Goel A, Butt AS, Sahney A, Shrestha A, Cárdenas A, Di Giorgio A, Arora A, Anand AC, Dhawan A, Jindal A, Saraya A, Srivastava A, Kumar A, Kaewdech A, Pande A, Rastogi A, Valsan A, Goel A, Kumar A, Singal AK, Tanaka A, Coilly A, Singh A, Meena BL, Jagadisan B, Sharma BC, Lal BB, Eapen CE, Yaghi C, Kedarisetty CK, Kim CW, Panackel C, Yu C, Kalal CR, Bihari C, Huang CH, Vasishtha C, Jansen C, Strassburg C, Lin CY, Karvellas CJ, Lesmana CRA, Philips CA, Shawcross D, Kapoor D, Agrawal D, Payawal DA, Praharaj DL, Jothimani D, Song DS, Kim DJ, Kim DS, Zhongping D, Karim F, Durand F, Shiha GE, D'Amico G, Lau GK, Pati GK, Narro GEC, Lee GH, Adali G, Dhakal GP, Szabo G, Lin HC, Li H, Nair HK, Devarbhavi H, Tevethia H, Ghazinian H, Ilango H, Yu HL, Hasan I, Fernandez J, George J, Behari J, Fung J, Bajaj J, Benjamin J, Lai JC, Jia J, Hu JH, Chen JJ, Hou JL, Yang JM, Chang J, Trebicka J, Kalf JC, Sollano JD, Varghese J, Arab JP, Li J, Reddy KR, Raja K, Panda K, Kajal K, Kumar K, Madan K, Kalista KF, Thanapirom K, Win KM, Suk KT, Devadas K, Lesmana LA, Kamani L, Premkumar M, Niriella MA, Al Mahtab M, Yuen MF, Sayed MHE, Alla M, Wadhawan M, Sharma MK, Sahu M, Prasad M, Muthiah MD, Schulz M, Bajpai M, Reddy MS, Praktiknjo M, Yu ML, Prasad M, Sharma M, Elbasiony M, Eslam M, Azam MG, Rela M, Desai MS, Vij M, Mahmud N, Choudhary NS, Marannan NK, Ormeci N, Saraf N, Verma N, Nakayama N, Kawada N, Oidov Baatarkhuu, Goyal O, Yokosuka O, Rao PN, Angeli P, Parikh P, Kamath PS, Thuluvath PJ, Lingohr P, Ranjan P, Bhangui P, Rathi P, Sakhuja P, Puri P, Ning Q, Dhiman RK, Kumar R, Vijayaraghavan R, Khanna R, Maiwall R, Mohanka R, Moreau R, Gani RA, Loomba R, Mehtani R, Rajaram RB, Hamid SS, Palnitkar S, Lal S, Biswas S, Chirapongsathorn S, Agarwal S, Sachdeva S, Saigal S, Kumar SE, Violeta S, Singh SP, Mochida S, Mukewar S, Alam S, Lim SG, Alam S, Shalimar, Venishetty S, Sundaram SS, Shetty S, Bhatia S, Singh SA, Kottilil S, Strasser S, Shasthry SM, Maung ST, Tan SS, Treeprasertsuk S, Asthana S, Manekeller S, Gupta S, Acharya SK, K C S, Maharshi S, Asrani S, Dadhich S, Taneja S, Giri S, Singh S, Chen T, Gupta T, Kanda T, Tanwandee T, Piratvishuth T, Spengler U, Prasad VGM, Midha V, Rakhmetova V, Arroyo V, Sood V, Br VK, Wong VWS, Pamecha V, Singh V, Dayal VM, Saraswat VA, Kim WR, Jafri W, Gu W, Jun WY, Qi X, Chawla YK, Kim YJ, Shi Y, Abbas Z, Kumar G, Shiina S, Wei L, Omata M, Sarin SK. Acute-on-chronic liver failure (ACLF): the 'Kyoto Consensus'-steps from Asia. Hepatol Int 2025; 19:1-69. [PMID: 39961976 PMCID: PMC11846769 DOI: 10.1007/s12072-024-10773-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Accepted: 12/29/2024] [Indexed: 02/23/2025]
Abstract
Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the 'Golden Therapeutic Window', the 'transplant window', and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The 'Kyoto APASL Consensus' presented below carries the final recommendations along with the relevant background information and areas requiring future studies.
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Affiliation(s)
- Ashok Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Vinod Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - A S Soin
- Medanta-The Medicity Hospital, Gurugram, Haryana, India
| | | | - Abhijeet Chowdhury
- Institute of Post-Graduate Medical Education and Research (IPGMER), Kolkata, West Bengal, India
| | - Abraham Koshy
- VPS Lakeshore Hospital and Research Center Ltd, Kochi, Kerala, India
| | - Ajay Duseja
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Ajay Kumar
- Govind Ballabh Pant Hospital, New Delhi, India
| | - Ajay Kumar Mishra
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | | | - Ajit Sood
- Dayanand Medical College, Ludhiana, India
| | - Akash Roy
- Apollo Multispeciality Hospital, Kolkata, India
| | - Akash Shukla
- Seth G S Medical College and K E M Hospital, Mumbai, Maharashtra, India
- Sir HN Reliance Foundation Hospital, Girgaon, Mumbai, Maharashtra, India
| | - Albert Chan
- Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | | | - Amar Mukund
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Amit Goel
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | | | | | | | - Andrés Cárdenas
- Univerity of Barcelona Institut d'Investigacions Biomèdiques August Pi-Sunyer, Barcelona, Spain
| | | | - Anil Arora
- Sir Ganga Ram Hospital, Rajender Nagar, New Delhi, India
| | - Anil Chandra Anand
- Kalinga Institute of Medical Sciences (KIMS), Bhubaneshwar, Orissa, India
| | | | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Anoop Saraya
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Anshu Srivastava
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | - Anupam Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Apurva Pande
- Fortis Hospital, Greater Noida, Uttar Pradesh, India
| | - Archana Rastogi
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Arun Valsan
- Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Kochi, India
| | - Ashish Goel
- Christian Medical College (CMC), Vellore, India
| | - Ashish Kumar
- Sir Ganga Ram Hospital, Rajender Nagar, New Delhi, India
| | - Ashwani K Singal
- University of Louisville School of Medicine, Trager Transplant Center and Jewish Hospital, Louisville, KY, USA
| | | | - Audrey Coilly
- Centre Hepato-Biliaire, Paul Brousse Hospital, Paris-Saclay University, Villejuif, France
| | - Ayaskanta Singh
- IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India
| | - Babu Lal Meena
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | | | - Bikrant Bihari Lal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - C E Eapen
- Christian Medical College (CMC), Vellore, India
| | - Cesar Yaghi
- Saint Joseph University, Hôtel-Dieu de France University Medical Center, Beirut, Lebanon
| | | | | | | | - Chen Yu
- Capital Medical University, Beijing, China
| | - Chetan R Kalal
- Nanavati Max Super Specialty Hospital, Mumbai, Maharashtra, India
| | - Chhagan Bihari
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Chitranshu Vasishtha
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Christian Jansen
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | | | - Chun Yen Lin
- Linkou Medical Centre, Chang Gung Memorial Hospital, Keelung, Taiwan
| | | | - Cosmas Rinaldi Adithya Lesmana
- Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Jakarta, Indonesia
- Medistra Hospital, Jakarta, Indonesia
| | | | | | | | | | | | | | | | | | | | - Dong-Sik Kim
- Korea University College of Medicine, Seoul, Republic of Korea
| | | | - Fazal Karim
- Sir Salimullah Medical College, Mitford Hospital, Dhaka, Bangladesh
| | - Francois Durand
- Université de Paris, AP-HP, C, DMU DIGEST, Centre de Référence Des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Centre de Recherche Sur L'inflammation, Inserm, Paris, France
| | | | - Gennaro D'Amico
- Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
- Clinica La Maddalena, Palermo, Italy
| | - George K Lau
- Humanity and Health Medical Center, Hongkong, SAR, China
| | | | - Graciela Elia Castro Narro
- Hospital Médica Sur, Mexico City, Mexico
- Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubiran",, Mexico City, Mexico
- Latin-American Association for the Study of the Liver (ALEH), Santiago de Chile, Chile
| | - Guan-Huei Lee
- National University Hospital, National University of Singapore, Singapore, Singapore
| | - Gupse Adali
- University of Health Sciences, Ümraniye, Istanbul, Turkey
| | | | - Gyongyi Szabo
- Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - H C Lin
- Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hai Li
- School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Hari Kumar Nair
- Ernakulam Medical Center (EMC), Kinder Multispeciality Hospital, Kochi, Kerala, India
| | | | - Harshvardhan Tevethia
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | | | | | - Irsan Hasan
- Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Jakarta, Indonesia
| | - J Fernandez
- University of Barcelona, IDIBAPS and CIBEREHD, Barcelona, Spain
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Jaideep Behari
- Pittsburgh Liver Research Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - James Fung
- Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | | | - Jaya Benjamin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Jennifer C Lai
- University of California, San Francisco, San Francisco, CA, USA
| | - Jidong Jia
- Capital Medical University, Beijing, China
| | - Jin Hua Hu
- The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, China
| | - Jin Jun Chen
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Jin Lin Hou
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China
| | - Jin Mo Yang
- The Catholic University of Korea, Seoul, Korea
| | - Johannes Chang
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Jonel Trebicka
- Medizinische Klinik B, Universitätsklinikum Münster, Münster, Germany
| | - Jörg C Kalf
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Jose D Sollano
- Department of Medicine, Cardinal Santos Medical Center, Manila, Philippines
| | - Joy Varghese
- Gleneagles Global Hospital, Chennai, Tamil Nadu, India
| | - Juan Pablo Arab
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
- Schulich School of Medicine, Western University, London, ON, Canada
| | - Jun Li
- The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China
| | | | - Kaiser Raja
- King's College Hospital London, Dubai, United Arab Emirates
| | - Kalpana Panda
- IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India
| | - Kamal Kajal
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Karan Kumar
- Mahatma Gandhi Medical College, Jaipur, Rajasthan, India
| | - Kaushal Madan
- Max Super Specialty Hospital Saket, New Delhi, India
| | - Kemal Fariz Kalista
- Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Jakarta, Indonesia
| | | | - Khin Maung Win
- University of Medicine, Yangon Ministry of Health, Yangon, Myanmar
| | - Ki Tae Suk
- Hallym University, Chuncheon, Republic of Korea
| | | | | | - Lubna Kamani
- Liaquat National Hospital, Karachi, Sindh, Pakistan
| | - Madhumita Premkumar
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | | | - Mamun Al Mahtab
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Man Fung Yuen
- Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | | | - Manasa Alla
- Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | | | - Manoj Kumar Sharma
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Manoj Sahu
- IMS and SUM Hospital, SOA University, Bhubaneswar, Odisha, India
| | - Manya Prasad
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Mark Dhinesh Muthiah
- National University Hospital, National University of Singapore, Singapore, Singapore
| | - Martin Schulz
- Goethe University Clinic Frankfurt, Frankfurt, Germany
| | - Meenu Bajpai
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | | | - Ming Lung Yu
- Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- College of Medicine, National Sun Yet-Sen University, Kaohsiung, Taiwan
| | | | - Mithun Sharma
- Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | | | - Mohammed Eslam
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW, Australia
| | - Mohd Golam Azam
- Endocrine and Metabolic Disorder (BIRDEM) Shahbad, Bangladesh Institute of Research and Rehabilitation in Diabetes, Dhaka, Bangladesh
| | - Mohd Rela
- Dr. Rela Institute and Medical Centre, Chennai, India
| | - Moreshwar S Desai
- Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA
| | - Mukul Vij
- Dr. Rela Institute and Medical Centre, Chennai, India
| | - Nadim Mahmud
- University of Pennsylvania, Philadelphia, PA, USA
| | | | | | - Necati Ormeci
- İstanbul Health and Technology University, Istanbul, Turkey
| | - Neeraj Saraf
- Medanta-The Medicity Hospital, Gurugram, Haryana, India
| | - Nipun Verma
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | | | - Norifumi Kawada
- Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Oidov Baatarkhuu
- Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | | | - Osamu Yokosuka
- Graduate School of Medicine, Chiba University, Chuo-Ku, Chiba, Japan
| | - P N Rao
- Asian Institute of Gastroenterology Hospitals, Hyderabad, India
| | - Paolo Angeli
- Department of Medicine (DIMED), University of Padova, Padua, Italy
| | | | | | | | - Philipp Lingohr
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Piyush Ranjan
- All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | | | - Pravin Rathi
- Topi Wala National (TN) Medical College and BYL Nair Charitable Hospital, Mumbai, India
| | | | - Puneet Puri
- Virginia Commonwealth University, Richmond, VA, USA
| | - Qin Ning
- Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - R K Dhiman
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | - Rahul Kumar
- Changi General Hospital, Singapore, Singapore
| | - Rajan Vijayaraghavan
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Rajeev Khanna
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Ravi Mohanka
- Sir HN Reliance Foundation Hospital, Girgaon, Mumbai, Maharashtra, India
| | - Richard Moreau
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
- Centre de Recherche Sur L'Inflammation (CRI), INSERM and Université Paris-Cité, Paris, France
- Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Beaujon, Service d'Hépatologie, Clichy, France
| | - Rino Alvani Gani
- Dr. Cipto Mangunkusumo National General Hospital, Medical Faculty Universitas Indonesia, Jakarta, Indonesia
| | - Rohit Loomba
- University of California, San Diego, La Jolla, CA, USA
| | - Rohit Mehtani
- Amrita Institute of Medical Sciences and Research Centre, Faridabad, Haryana, India
| | | | - S S Hamid
- Aga Khan University Hospital, Karachi, Pakistan
| | | | - Sadhna Lal
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Sagnik Biswas
- All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | | | - Samagra Agarwal
- All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | | | - Sanjiv Saigal
- Max Super Specialty Hospital Saket, New Delhi, India
| | | | | | - Satender Pal Singh
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Saurabh Mukewar
- Midas Multispeciality Hospital Pvt. Ltd, Nagpur, Maharashtra, India
| | - Seema Alam
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Seng Gee Lim
- National University Hospital, National University of Singapore, Singapore, Singapore
| | - Shahinul Alam
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Shalimar
- All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | | | | | - Shiran Shetty
- Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Shobna Bhatia
- National Institute of Medical Sciences, Jaipur, India
| | | | - Shyam Kottilil
- University of Maryland School of Medicine, Baltimore, USA
| | | | - S M Shasthry
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Soek Siam Tan
- Selayang Hospital, University of Malaysia, Batu Caves, Selangor, Malaysia
| | | | | | | | - Subhash Gupta
- Max Super Specialty Hospital Saket, New Delhi, India
| | | | - Sudhamshu K C
- Bir Hospital, National Academy of Medical Sciences, Kathmandu, Nepal
| | - Sudhir Maharshi
- Sawai Man Singh (SMS) Medical College and Hospital, Jaipur, Rajasthan, India
| | - Sumeet Asrani
- Baylor Simmons Transplant Institute, Dallas, TX, USA
| | - Sunil Dadhich
- Dr Sampuranand Medical College (SNMC), Jodhpur, Rajasthan, India
| | - Sunil Taneja
- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Suprabhat Giri
- Kalinga Institute of Medical Sciences (KIMS), Bhubaneshwar, Orissa, India
| | - Surender Singh
- Sanjay Gandhi Post Graduate Institute (SGPGI), Lucknow, Uttar Pradesh, India
| | - Tao Chen
- Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tarana Gupta
- Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India
| | - Tatsuo Kanda
- Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | | | | | - Ulrich Spengler
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - V G Mohan Prasad
- Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA
| | | | | | - Vicente Arroyo
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), Barcelona, Spain
| | - Vikrant Sood
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Vinay Kumar Br
- Mazumdar Shaw Medical Centre, Bangalore, Karnataka, India
| | | | - Viniyendra Pamecha
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Virendra Singh
- Punjab Institute of Liver and Biliary Sciences, Mohali, Punjab, India
| | - Vishwa Mohan Dayal
- Indira Gandhi Institute of Medical Sciences, (IGIMS), Bely Road Patna, Bihar, India
| | | | - WRay Kim
- Stanford University, Stanford, CA, USA
| | - Wasim Jafri
- Aga Khan University Hospital, Karachi, Pakistan
| | - Wenyi Gu
- Goethe University Clinic Frankfurt, Frankfurt, Germany
| | - Wong Yu Jun
- Changi General Hospital, Singapore, Singapore
| | - Xiaolong Qi
- Medical School, Zhongda Hospital, Southeast University, Nanjing, China
| | - Yogesh K Chawla
- Kalinga Institute of Medical Sciences (KIMS), Bhubaneshwar, Orissa, India
| | - Yoon Jun Kim
- Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yu Shi
- The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China
| | - Zaigham Abbas
- Ziauddin University Hospital Karachi, Karachi, Pakistan
| | - Guresh Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | - Lai Wei
- Changgung Hospital, Tsinghua University, Beijing, China
| | - Masao Omata
- Yamanashi Central Hospital, Yamanashi, Japan
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.
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Zhang X, Huang H, Wang J, Wei B. Efficacy of Contezolid in the Treatment of Catheter-Related Bloodstream Infections Caused by Methicillin-Resistant Staphylococcus aureus in a Patient with Hepatorenal Syndrome and Acute Kidney Injury: A Case Report. Infect Drug Resist 2025; 18:307-311. [PMID: 39835163 PMCID: PMC11745060 DOI: 10.2147/idr.s501604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 12/25/2024] [Indexed: 01/22/2025] Open
Abstract
The Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI) patients infected with methicillin-resistant Staphylococcus aureus (MRSA) urgently require safe and effective treatment options due to their compromised hepatic and renal functions, as well as thrombocytopenia resulting from hypersplenism. In our case, an HRS-AKI patient who underwent continuous renal replacement therapy for fluid overload developed fever with chills. His blood tests indicated elevated C-reactive protein and neutrophils, low platelet count, and bilateral lung infiltrates. Subsequently, his blood culture and catheter culture confirmed a catheter-related MRSA bloodstream infection. To address this complex clinical challenge, a novel oxazolidinone antibiotic, contezolid (800mg orally every 12 hours), was introduced into the patient's anti-infection regimen. Notably, the patient exhibited remarkable improvements and responded favorably to this treatment. During subsequent follow-up, no recurrence of the infection or drug-related adverse events was observed. The successful utilization of contezolid in this case underscores its potential as a novel therapeutic option for treating MRSA infections in patients with HRS-AKI.
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Affiliation(s)
- Xiucui Zhang
- Department of Infectious Disease, Changzheng Hospital, Navy Medical University, Shanghai, People’s Republic of China
| | - Huili Huang
- Department of Infectious Disease, Changzheng Hospital, Navy Medical University, Shanghai, People’s Republic of China
| | - Jianrong Wang
- Department of Infectious Disease, Changzheng Hospital, Navy Medical University, Shanghai, People’s Republic of China
| | - Bo Wei
- Department of Infectious Disease, Changzheng Hospital, Navy Medical University, Shanghai, People’s Republic of China
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18
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Hackstein CP. Liver damage and immune responses. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:56-64. [PMID: 39793602 DOI: 10.1055/a-2365-3796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2025]
Abstract
Chronic liver disease (CLD) has massive systemic repercussions including major impacts on the body's immune system. Abnormalities in phenotype, function and numbers of various immune cell subsets have been established by a large number of clinical and pre-clinical studies. The loss of essential immune functions renders CLD-patients exceptionally susceptible to bacterial and viral infections and also impairs the efficacy of vaccination. Consequently, infections represent a major clinical issue causing significant morbidity and mortality in these patients. Mechanistically, the immune dysfunction associated with CLD results from the increased translocation of bacteria and bacterial cues from the intestine. These trigger a signaling axis around the cytokines IFN I and IL-10 in hepatic myeloid cells, which aside from impairing the function of the myeloid cells themselves, also has notable negative impacts on the functionality of other immune cells. T cells in CLD-patients and -models are especially affected by this signaling axis and display a variety of quantitative and qualitative defects. Due to the high clinical relevance, understanding the mechanisms underlaying CED-associated immune dysfunction is of critical importance to discover and develop new therapeutic targets.
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Affiliation(s)
- Carl-Philipp Hackstein
- Institut für Molekulare Immunologie, Technische Universität München, München, Germany
- Zentrum für Infektionsprävention (ZIP), Technische Universität München, Freising, Germany
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19
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Kronsten VT, Shawcross DL. Clinical Implications of Inflammation in Patients With Cirrhosis. Am J Gastroenterol 2025; 120:65-74. [PMID: 39194320 PMCID: PMC11676607 DOI: 10.14309/ajg.0000000000003056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 08/19/2024] [Indexed: 08/29/2024]
Abstract
Cirrhosis-associated immune dysfunction refers to the concurrent systemic inflammation and immunoparesis evident across the disease spectrum of chronic liver disease, ranging from the low-grade inflammatory plasma milieu that accompanies compensated disease to the intense high-grade inflammatory state with coexistent severe immune paralysis that defines acute decompensation and acute-on-chronic liver failure. Systemic inflammation plays a crucial role in the disease course of cirrhosis and is a key driver for acute decompensation and the progression from compensated to decompensated cirrhosis. Severe systemic inflammation is fundamental to the development of organ dysfunction and failure and, in its most extreme form, acute-on-chronic liver failure. Systemic inflammation propagates the development of hepatic encephalopathy and hepatorenal syndrome-acute kidney injury. It may also be involved in the pathogenesis of further complications such as hepatocellular carcinoma and mental illness. Those patients with the most profound systemic inflammation have the worst prognosis. Systemic inflammation exerts its negative clinical effects through a number of mechanisms including nitric oxide-mediated increased splanchnic vasodilation, immunopathology, and metabolic reallocation.
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Affiliation(s)
- Victoria T. Kronsten
- Institute of Liver Studies, Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London
- Institute of Liver Studies, King's College Hospital, Denmark Hill, London
| | - Debbie L. Shawcross
- Institute of Liver Studies, Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London
- Institute of Liver Studies, King's College Hospital, Denmark Hill, London
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20
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Haedge F, Bruns T. Antibiotics in decompensated liver disease - who, when and for how long? Expert Rev Gastroenterol Hepatol 2025; 19:111-130. [PMID: 39921440 DOI: 10.1080/17474124.2025.2464044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 01/26/2025] [Accepted: 02/04/2025] [Indexed: 02/10/2025]
Abstract
INTRODUCTION Bacterial infections are a leading cause of hospitalization and mortality in patients with decompensated cirrhosis. Antibiotic prophylaxis in cirrhotic patients has demonstrated significant short-term reductions in bacterial infections in randomized controlled trials, but at the cost of drug resistance and with uncertain survival benefits. AREAS COVERED This review examines antibiotic use in cirrhosis, focusing on patients most likely to benefit from antibiotic prophylaxis, management strategies for infections through risk-based antibiotic selection and timely treatment initiation, challenges posed by the emergence of multidrug-resistant organisms, and principles of antimicrobial stewardship. EXPERT OPINION The efficacy of prophylaxis has decreased over time, and current registry data have questioned its use, emphasizing the need for better risk-based individualized strategies. When bacterial infections occur, the efficacy of antimicrobial therapies depends heavily on local epidemiological patterns and individual patient risk factors, necessitating tailored antibiotic selection based on regional resistance data and specific clinical scenarios. Nosocomial infections, colonization with multidrug-resistant organisms, and prior exposure to systemic antibiotics are key risk factors that should guide empirical therapy selection. Until evidence-based algorithms are available, clinicians should continue to adopt individualized approaches, guided by available evidence, local specificities, and antimicrobial stewardship principles to optimize patient outcomes.
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Affiliation(s)
- Frederic Haedge
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Tony Bruns
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany
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21
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Protopapas AA, Tsankof A, Papagiouvanni I, Kaiafa G, Skoura L, Savopoulos C, Goulis I. Outpatient management after hospitalisation for acute decompensation of cirrhosis: A practical guide. World J Hepatol 2024; 16:1377-1394. [DOI: 10.4254/wjh.v16.i12.1377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 10/24/2024] [Accepted: 11/20/2024] [Indexed: 11/29/2024] Open
Abstract
Acute decompensation in cirrhotic patients signifies the onset of clinically evident events due to portal hypertension. The transition from compensated to decompensated cirrhosis involves hemodynamic changes leading to multiorgan dysfunction, managed predominantly in outpatient settings with regular monitoring. The mortality risk is elevated in decompensated patients. Therefore, diligent outpatient management should focus on regular medical follow-ups, medication adjustments, patient education, addressing emergent issues and evaluation for liver transplantation. The ultimate goal is to improve quality of life, prevent disease progression, reduce complications, and assess possible recompensation. This guide provides valuable recommendations for medical experts managing decompensated cirrhotic patients post-hospitalization.
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Affiliation(s)
- Adonis A Protopapas
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki 54636, Greece
| | - Alexandra Tsankof
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki 54636, Greece
| | - Ioanna Papagiouvanni
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital, Thessaloniki 54642, Greece
| | - Georgia Kaiafa
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki 54636, Greece
| | - Lemonia Skoura
- Department of Microbiology, Aristotle University οf Thessaloniki, AHEPA University Hospital, Thessaloniki 54636, Greece
| | - Christos Savopoulos
- First Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki 54636, Greece
| | - Ioannis Goulis
- Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital, Thessaloniki 54642, Greece
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22
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Li Y, Niu B, Liu J, Zhou H, Chen Z, Zhou Y, Wei Q, Jiao X, Mi Y, Li P. Bacterial infection adversely increases the risk of decompensation in patients with hepatitis B virus-related compensated cirrhosis: a retrospective study. BMC Infect Dis 2024; 24:1446. [PMID: 39695967 DOI: 10.1186/s12879-024-10306-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 12/04/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Hepatitis B virus related compensated cirrhosis generally has a favorable prognosis until decompensation occurs. Bacterial infections are prevalent in Hepatitis B virus related decompensated cirrhosis.Bacterial infection and decompensated hepatitis B cirrhosis are mutually reinforcing. And it also interacts with and promotes certain decompensation-related events. However, the impact of bacterial infections on the progression from compensated to decompensated cirrhosis in Hepatitis B patients remains unclear. METHODS We retrospectively analyzed the baseline characteristics of 1,011 patients with Hepatitis B virus related compensated cirrhosis. Using time-dependent regression analysis, we evaluated whether bacterial infections increase the risk of decompensation, defined as the occurrence of ascites, hepatic encephalopathy, or variceal bleeding. RESULTS A total of 1,011 patients were retrospectively analyzed over a median follow-up period of 79 months. Bacterial infections were observed in 89 patients (8.8%). Respiratory and urinary tract infections were the most common bacterial infections.Decompensation occurred in 44.9% of patients with bacterial infections, compared to 9% of those without BIs. Patients with bacterial infections had a higher risk of decompensation ([OR] 1.024; 95% CI 1.016-1.032; p < 0.001) than those without bacterial infections. CONCLUSION Our findings suggest that bacterial infections have a significant impact on the progression of hepatitis B virus related compensated cirrhosis, notably increasing the risk of decompensation.
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Affiliation(s)
- Yinglun Li
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Bin Niu
- Department of Infectious Diseases, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Jing Liu
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Hui Zhou
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
| | - Ze Chen
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Yibing Zhou
- Department of Scientific Research, Central Laboratory, Changshu Hospital Affiliated to Soochow University, Changshu No.1 People's Hospital, Changshu, 215500, China
| | - Qian Wei
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Xue Jiao
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
- Clinical School of the Second People's Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yuqiang Mi
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
- Tianjin Research Institute of Liver Diseases, Tianjin, China
| | - Ping Li
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China.
- Tianjin Research Institute of Liver Diseases, Tianjin, China.
- Second Department of Integrated Traditional Chinese and Western Medicine, Tianjin Second People's Hospital, Tianjin, China.
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23
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Acevedo-Haro JG, Mohamed W, Moodley P, Bendall O, Bennett K, Keelty N, Chan S, Waddy S, Hosking J, Thomas W, Tilley R. Sensitivity of diagnosis of spontaneous bacterial peritonitis is higher with the automated cell count method. World J Hepatol 2024; 16:1265-1281. [PMID: 39606172 PMCID: PMC11586750 DOI: 10.4254/wjh.v16.i11.1265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 09/09/2024] [Accepted: 09/25/2024] [Indexed: 11/06/2024] Open
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP) is one of the most important complications of patients with liver cirrhosis entailing high morbidity and mortality. Making an accurate early diagnosis of this infection is key in the outcome of these patients. The current definition of SBP is based on studies performed more than 40 years ago using a manual technique to count the number of polymorphs in ascitic fluid (AF). There is a lack of data comparing the traditional cell count method with a current automated cell counter. Moreover, current international guidelines do not mention the type of cell count method to be employed and around half of the centers still rely on the traditional manual method. AIM To compare the accuracy of polymorph count on AF to diagnose SBP between the traditional manual cell count method and a modern automated cell counter against SBP cases fulfilling gold standard criteria: Positive AF culture and signs/symptoms of peritonitis. METHODS Retrospective analysis including two cohorts: Cross-sectional (cohort 1) and case-control (cohort 2), of patients with decompensated cirrhosis and ascites. Both cell count methods were conducted simultaneously. Positive SBP cases had a pathogenic bacteria isolated on AF and signs/symptoms of peritonitis. RESULTS A total of 137 cases with 5 positive-SBP, and 85 cases with 33 positive-SBP were included in cohort 1 and 2, respectively. Positive-SBP cases had worse liver function in both cohorts. The automated method showed higher sensitivity than the manual cell count: 80% vs 52%, P = 0.02, in cohort 2. Both methods showed very good specificity (> 95%). The best cutoff using the automated cell counter was polymorph ≥ 0.2 cells × 109/L (equivalent to 200 cells/mm3) in AF as it has the higher sensitivity keeping a good specificity. CONCLUSION The automated cell count method should be preferred over the manual method to diagnose SBP because of its higher sensitivity. SBP definition, using the automated method, as polymorph cell count ≥ 0.2 cells × 109/L in AF would need to be considered in patients admitted with decompensated cirrhosis.
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Affiliation(s)
- Juan G Acevedo-Haro
- South West Liver Unit, University Hospitals Plymouth NHS Trust, Plymouth PL6 8DH, United Kingdom
- Peninsula Medical School, University of Plymouth, Plymouth PL6 8DH, United Kingdom.
| | - Waddah Mohamed
- South West Liver Unit, University Hospitals Plymouth NHS Trust, Plymouth PL6 8DH, United Kingdom
| | - Prebashan Moodley
- South West Liver Unit, University Hospitals Plymouth NHS Trust, Plymouth PL6 8DH, United Kingdom
| | - Oliver Bendall
- South West Liver Unit, University Hospitals Plymouth NHS Trust, Plymouth PL6 8DH, United Kingdom
| | - Kris Bennett
- South West Liver Unit, University Hospitals Plymouth NHS Trust, Plymouth PL6 8DH, United Kingdom
| | - Nigel Keelty
- South West Liver Unit, University Hospitals Plymouth NHS Trust, Plymouth PL6 8DH, United Kingdom
| | - Sally Chan
- South West Liver Unit, University Hospitals Plymouth NHS Trust, Plymouth PL6 8DH, United Kingdom
| | - Sam Waddy
- Intensive Care Unit, University Hospitals Plymouth NHS Trust, Plymouth PL6 8DH, United Kingdom
| | - Joanne Hosking
- Medical Statistics Group, Peninsula Clinical Trials Unit, University of Plymouth, Plymouth PL6 8DH, United Kingdom
| | - Wayne Thomas
- Haematology Service, University Hospitals Plymouth NHS Trust, Plymouth PL6 8DH, United Kingdom
| | - Robert Tilley
- Microbiology Service, University Hospitals Plymouth NHS Trust, Plymouth PL6 8DH, United Kingdom
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24
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Shen Y, Xu W, Chen Y, Wen S, Chen Q, Liu S, Zhu X, Tang LL, Li L, Ju B. Early prediction of acute-on-chronic liver failure development in patients with diverse chronic liver diseases. Sci Rep 2024; 14:28245. [PMID: 39548240 PMCID: PMC11568263 DOI: 10.1038/s41598-024-79486-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 11/11/2024] [Indexed: 11/17/2024] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a syndrome characterized by the acute decompensation of chronic liver disease, resulting in organ failure and high short-term mortality. The progression of ACLF is dynamic and reversible in a considerable proportion of patients during hospitalization. Early detection and accurate assessment of ACLF are essential; however, ideal methods for this purpose are still lacking. Therefore, this study aimed to develop a new score for predicting the onset of ACLF in patients with various chronic liver diseases.A total of 6,188 patients with various chronic liver diseases were included in the study. Clinical and laboratory data were collected, and the occurrence of ACLF within 28 days was recorded. The Lasso-Cox regression method was employed to develop prediction models for the onset of ACLF at 7, 14, and 28 days. Among 5,221 patients without ACLF, 477 progressed to ACLF within 28 days. Seven predictors were identified as significantly associated with the occurrence of ACLF at 7, 14, and 28 days. A new scoring system was developed as follows: [NEUT ≥ 7, 109/L; 1 or 0] × 0.49 + [PLT < 100, 109/L; 1 or 0] × 0.44 + [TBIL ≥ 35, µmol/L; 1 or 0] × 0.05 + [HDL-C < 0.5, mmol/L; 1 or 0] × 1.04 - Ln[Hb, g/L] × 0.89 + [BUN > 7, mmol/L; 1 or 0] × 0.51 + Ln[INR] × 0.87 + 3.40. This new score demonstrated superior discrimination, with the C-indexes of 0.958, 0.944, and 0.938 at 7, 14, and 28 days, respectively, outperforming those of four other scores (CLIF-C-ACLF-Ds, MELD, MELD-Na, and CLIF-C-ADs score; all P < 0.001). Additionally, the new score improved in predictive accuracy, time-dependent receiver operating characteristics, probability density function evaluations, and calibration curves, making it highly predictive for the onset of ACLF at all time points. The optimal cut-off value of 9.6 effectively distinguished between high- and low-risk patients for ACLF onset. These findings were further validated in a separate cohort of patients. A new progressive score, based on seven predictors, has been developed to accurately forecast the occurrence of ACLF within 7, 14, and 28 days in patients with various chronic liver diseases. This tool may be utilized to identify high-risk patients, tailor follow-up management, and guide the escalation of care, prognostication, and transplant evaluation.
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Affiliation(s)
- Yuqiang Shen
- Department of Information Technology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
- School of Computer Science and Technology, Zhejiang Sci-Tech University, Hangzhou, China
| | - Wan Xu
- Hangzhou Xiaoshan District Center for Disease Control and Prevention (Hangzhou Xiaoshan District Health Supervision Institute), Hangzhou, China
| | - Yang Chen
- Department of Information Technology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
| | | | - Qijiong Chen
- Hangzhou Xiaoshan District Center for Disease Control and Prevention (Hangzhou Xiaoshan District Health Supervision Institute), Hangzhou, China
| | - Shanna Liu
- Department of Information Technology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
| | - Xinjian Zhu
- Department of Information Technology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China
| | - Ling-Ling Tang
- Department of Infectious Diseases, Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China.
| | - Li Li
- Department of Hepatobiliary Surgery, The First People's Hospital of Kunming, Kunming, China.
| | - Bin Ju
- SanOmics AI Co., Ltd, Hangzhou, China.
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25
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Cao Z, Wong F, Choudhury AK, Kamath PS, Topazian M, Torre A, Hayes PC, George J, Idilman R, Seto WK, Desalegn H, Alvares-da-Silva MR, Bush BJ, Thacker LR, Xie Q, Bajaj JS. Global prevalence and characteristics of infections and clinical outcomes in hospitalised patients with cirrhosis: a prospective cohort study for the CLEARED Consortium. Lancet Gastroenterol Hepatol 2024; 9:997-1009. [PMID: 39243795 DOI: 10.1016/s2468-1253(24)00224-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 06/30/2024] [Accepted: 07/03/2024] [Indexed: 09/09/2024]
Abstract
BACKGROUND Infections have a poor prognosis in inpatients with cirrhosis. We aimed to determine regional variations in infections and their association with clinical outcomes in a global cohort of inpatients with cirrhosis. METHODS In this prospective cohort study initiated by the CLEARED Consortium, we enrolled adults (aged >18 years) with cirrhosis who were non-electively admitted to 98 hospitals from 26 countries or regions across six continents between Nov 5, 2021, and Dec 10, 2022. Data at admission, during hospitalisation, and for 30 days after discharge were collected through patient reports and chart reviews. Collected data included demographics; country and country income level per World Bank classifications (high-income countries [HICs], upper-middle-income countries [UMICs], and low-income or lower-middle-income countries [L-LMICs]); comorbidities; characteristics related to cirrhosis and the infections, including types, culture results, and drug resistance profile; antibiotic use; and disease course while hospitalised and for 30 days post-discharge. The primary outcome was in-hospital death or hospice referral in those with versus those without an admission infection (defined by the presence of infection on or within 48 h of admission). Multivariable log-binomial regression for in-hospital death or hospice referral was performed to identify risk factors. FINDINGS Of 4550 patients screened, 4238 patients (mean age 56·1 years [SD 13·3]; 2711 [64·0%] male and 1527 [36·0%] female) with complete data were enrolled. 1351 (31·9%) had admission infections. A higher proportion of patients in L-LMICs had infections (318 [41·7%] of 762 vs 444 [58·3%] without infection) than in UMICs (588 [30·6%] of 1922 vs 1334 [69·4%]) or HICs (445 [28·6%] of 1554 vs 1109 [71·4%]). Patients with admission infections had worse severity of cirrhosis and were more likely to have had an infection or been hospitalised in the preceding 6 months. The most common specific infection types were spontaneous bacterial peritonitis (391 [28·9%] of 1351), pneumonia (233 [17·2%]), and urinary tract infections (193 [14·3%]). 549 (40·6%) patients were culture-positive for bacterial or fungal infections, with the lowest culture-positive rates in Africa and mainland China. Most of the isolated organisms were Gram-negative (345 [63%] of 549), then Gram-positive (157 [29%]), and then fungi or mixed (47 [9%]), with Escherichia coli, Klebsiella pneumoniae, and Enterococcus spp being the top three isolated pathogens. The overall rate of drug resistance was 40% (220 of 549 with positive cultures), being highest in UMICs. The most used empirical antimicrobials were third-generation cephalosporins (453 [37%] of 1241), followed by the broad-spectrum β-lactams and β-lactamase inhibitors (289 [23%]). De-escalation was observed in 62 (20%) of 304 patients who had their antibiotics changed. Patients with versus without admission infections had a higher rate of in-hospital death or hospice transfer (299 [22·1%] of 1351 vs 232 [8·0%] of 2887; p<0·0001), a result replicated in multivariable analysis (adjusted risk ratio 1·75 [95% CI 1·42-2·06]; p<0·0001). Older age, self-reported female gender, not being in a HIC, lactulose use, and higher MELD-Na score were also associated with in-hospital death or hospice transfer on multivariable analysis. INTERPRETATION In the CLEARED Consortium cohort of inpatients with cirrhosis, the rates and types of infections, causative organisms, and culture-positivity varied substantially across regions, and infections were associated with a higher mortality risk. Culture positivity, which guides appropriate antibiotic use, was low. Taking a global perspective, considering regional variations in infections, drug resistance, and resources, could help to alleviate disparities in burden and outcomes. FUNDING US Department of Veterans Affairs, the Richmond Institute for Veterans Research, the National Natural Science Foundation of China, Shanghai Rising-Star Program, the National Council for Scientific and Technological Development of Brazil, and Shanghai Municipal Key Clinical Specialty.
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Affiliation(s)
- Zhujun Cao
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Florence Wong
- Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Ashok K Choudhury
- Department of Hepatology, Institute for Liver and Biliary Sciences, New Delhi, India
| | - Patrick S Kamath
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Mark Topazian
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; Gastroenterology and Hepatology Unit, St Paul's Hospital, Millennium Medical College, Addis Ababa, Ethiopia
| | - Aldo Torre
- Department of Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Peter C Hayes
- Hepatology, Division of Health Sciences, Deanery of Clinical Sciences, University of Edinburgh, Edinburgh, UK
| | - Jacob George
- Storr Liver Centre, The Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, Sydney, NSW, Australia
| | - Ramazan Idilman
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Wai-Kay Seto
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Hailemichael Desalegn
- Gastroenterology and Hepatology Unit, St Paul's Hospital, Millennium Medical College, Addis Ababa, Ethiopia
| | - Mario Reis Alvares-da-Silva
- Department of Hepatology, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Brian J Bush
- Department of Population Health, Virginia Commonwealth University, Richmond, VA, USA
| | - Leroy R Thacker
- Department of Population Health, Virginia Commonwealth University, Richmond, VA, USA
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology, and Nutrition and Richmond VA Medical Center, Virginia Commonwealth University, Richmond, VA, USA.
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26
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Pompili E, Iannone G, Carrello D, Zaccherini G, Baldassarre M, Caraceni P. Managing Multiorgan Failure in Acute on Chronic Liver Failure. Semin Liver Dis 2024; 44:492-509. [PMID: 39442531 DOI: 10.1055/a-2448-0664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2024]
Abstract
Acute-on-chronic liver failure (ACLF) is defined as a clinical syndrome that develops in patients with chronic liver disease characterized by the presence of organ failure and high short-term mortality, although there is still no worldwide consensus on diagnostic criteria. Management of ACLF is mainly based on treatment of "precipitating factors" (the most common are infections, alcohol-associated hepatitis, hepatitis B flare, and bleeding) and support of organ failure, which often requires admission to the intensive care unit. Liver transplantation should be considered in patients with ACLF grades 2 to 3 as a potentially life-saving treatment. When a transplant is not indicated, palliative care should be considered after 3 to 7 days of full organ support in patients with at least four organ failures or a CLIF-C ACLF score of >70. This review summarizes the current knowledge on the management of organ failure in patients with ACLF, focusing on recent advances.
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Affiliation(s)
- Enrico Pompili
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giulia Iannone
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Daniele Carrello
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giacomo Zaccherini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Maurizio Baldassarre
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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Ravindranath A, Srivastava A, Yachha SK, Poddar U, Sarma MS, Mathias A. Prevalence and Precipitants of Hepatic Encephalopathy in Hospitalized Children With Chronic Liver Disease. J Clin Exp Hepatol 2024; 14:101452. [PMID: 39005950 PMCID: PMC11245966 DOI: 10.1016/j.jceh.2024.101452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 05/25/2024] [Indexed: 07/16/2024] Open
Abstract
Objective Hepatic encephalopathy (HE) is a marker of poor prognosis in adults with chronic liver disease (CLD). We prospectively studied the prevalence and precipitants of HE in children with CLD as there is a paucity of literature on the same. Methods Children (1-18 years) admitted with CLD were examined daily for the presence and grading of HE (West Haven/Whittington grading). Precipitants were classified as infection, dyselectrolytemia, gastrointestinal bleeding, constipation and dehydration. Changes in grades of HE and outcome were noted. Results One hundred and sixty children (age 120 [84-168] months) were enrolled. HE was present in 50 (31.2%) patients with a total of 61 episodes. Maximum grade of HE was grade I (n = 16), II (n = 23), III (n = 11) and IV (n = 11). Forty-two cases had single and 8 had recurrent (2-5) episodes. Median duration of HE episodes was 96 (72-192) hours. Precipitants were identified in 55/61 (90.2%) episodes with infection (45/61, 73.7%) and dyselectrolytemia (33/61, 54%) being the most common. Lower albumin and sodium, higher INR and presence of infection were significantly associated with presence of HE. Overall, HE resolved in 33 (54%) episodes, while it progressed and persisted in 28 (45.9%) episodes. Patients with HE had a poorer outcome (25/50 vs 13/110; P < 0.01) with both higher in-hospital (11/50 vs 9/110; P = 0.02) and 1-month post discharge (14/39 vs 4/101; P < 0.01) mortality than those without HE. Conclusion One-third of admitted CLD children have HE, with identifiable precipitants in 90% of cases. Children with HE have poorer liver functions, higher rate of infections and worse outcome than those without HE.
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Affiliation(s)
- Aathira Ravindranath
- Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Anshu Srivastava
- Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Surender K Yachha
- Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Ujjal Poddar
- Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Moinak S Sarma
- Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Amrita Mathias
- Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
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Ferrarese A, Senzolo M, Sasset L, Bassi D, Cillo U, Burra P. Multidrug-resistant bacterial infections in the liver transplant setting. Updates Surg 2024; 76:2521-2529. [PMID: 38918314 PMCID: PMC11602820 DOI: 10.1007/s13304-024-01903-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 05/21/2024] [Indexed: 06/27/2024]
Abstract
Bacterial infections pose a life-threatening complication in patients with decompensated liver cirrhosis and acute-on-chronic liver failure. An increasing prevalence of infections caused by multidrug-resistant organisms (MDROs) has been observed in these patients, significantly impacting prognosis. A growing body of evidence has identified the most common risk factors for such infections, enabling the development of preventive strategies and therapeutic interventions. MDRO infections may also occur after liver transplantation (most commonly in the early post-operative phase), affecting both graft and patient survival. This review provides an overview of MDRO infections before and after liver transplantation, discussing epidemiological aspects, risk factors, prevention strategies, and novel therapeutic approaches. Furthermore, it examines the implications of MDRO infections in the context of prioritizing liver transplantation for the most severe patients, such as those with acute-on-chronic liver failure.
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Affiliation(s)
- Alberto Ferrarese
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy.
| | - Marco Senzolo
- Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Lolita Sasset
- Infectious Disease Unit, Padua University Hospital, Padua, Italy
| | - Domenico Bassi
- Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Umberto Cillo
- Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
- Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
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29
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Clària J, Aguilar F, Lozano JJ, Jiménez-Gracia L, Nieto JC, Romero-Grimaldo B, Marcos-Fa X, Giarracco E, Weiss E, Trebicka J, Hernàndez I, Fernandez J, Casulleras M, López-Vicario C, Muldur S, Hopke A, Vlagea A, Aransay AM, Marchese D, Bernardi M, Jalan R, Angeli P, Magri G, Cerutti A, Irimia D, Heyn H, Arroyo V, Moreau R. Albumin reprograms the B cell transcriptional landscape and improves neutrophil antimicrobial function in patients with decompensated cirrhosis. JHEP Rep 2024; 6:101184. [PMID: 39434891 PMCID: PMC11490805 DOI: 10.1016/j.jhepr.2024.101184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 07/26/2024] [Accepted: 07/31/2024] [Indexed: 10/23/2024] Open
Abstract
Background & Aims Patients with acutely decompensated (AD) cirrhosis are immunocompromised and particularly susceptible to infections. This study investigated the immunomodulatory actions of albumin by which this protein may lower the incidence of infections. Methods Blood immunophenotyping was performed in 11 patients with AD cirrhosis and 10 healthy volunteers (HV). Bulk and single-cell RNA sequencing (scRNA-seq) and flow cytometry were performed in peripheral blood mononuclear cells (PBMCs) from 20 patients with AD cirrhosis and 34 HV exposed to albumin. Albumin's effects on degranulation, phagocytosis, chemotaxis, and swarming of neutrophils from six patients with AD cirrhosis and nine HV were assessed by measuring myeloperoxidase enzymatic activity, the engulfment of fluorescent-labeled Escherichia coli and zymosan, and interactions of neutrophils with Candida albicans at single-cell resolution in microfluidic chambers, respectively. Whole blood RNA sequencing (RNA-seq) analyses were performed in 49 patients admitted for severe AD cirrhosis, of whom 30 received albumin during hospitalization. Results Compared with HV, patients with AD cirrhosis showed severe lymphopenia and defective neutrophil antimicrobial function. Bulk and scRNA-seq analyses revealed significantly (false discovery rate [FDR] <0.05) increased signatures related to B cells, myeloid cells, and CD4+ T cells in PBMCs incubated with albumin. Changes in the B cell population were confirmed by flow cytometry. Neutrophils exposed to albumin also exhibited augmented chemotactic and degranulation responses, enhanced phagocytosis, and increased pathogen-restrictive swarming. RNA-seq data analysis in patients who had received albumin revealed specific upregulation of signatures related to B cells and neutrophils together with transcriptional changes in CD4+ T cells (FDR <0.05). Conclusions The finding that albumin promotes the transcriptional reprogramming and expansion of the B cell compartment and improves neutrophil antimicrobial functions indicates mechanisms that may lower the incidence of infections in patients with severe AD cirrhosis receiving albumin therapy. Impact and implications Patients with acutely decompensated cirrhosis receiving albumin as treatment have a lower incidence of infections. The reason for this protection is currently unknown, but the present study provides data that support the ability of albumin to boost the antimicrobial functions of immune cells in these patients. Moreover, these findings encourage the design of controlled clinical studies specifically aimed at investigating the effects of albumin administration on the immune system.
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Affiliation(s)
- Joan Clària
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), European Association for the Study of the Liver (EASL)–CLIF Consortium, and Grifols Chair, Barcelona, Spain
- Hospital Clínic-IDIBAPS, Barcelona, Spain
- CIBER of Hepatic and Digestive Diseases (CIBERehd); Barcelona, Spain
- Universitat de Barcelona, Barcelona, Spain
| | - Ferran Aguilar
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), European Association for the Study of the Liver (EASL)–CLIF Consortium, and Grifols Chair, Barcelona, Spain
| | - Juan-José Lozano
- CIBER of Hepatic and Digestive Diseases (CIBERehd); Barcelona, Spain
| | - Laura Jiménez-Gracia
- Universitat de Barcelona, Barcelona, Spain
- Centre Nacional d’Anàlisi Genòmica (CNAG), Barcelona, Spain
| | - Juan C. Nieto
- Universitat de Barcelona, Barcelona, Spain
- Centre Nacional d’Anàlisi Genòmica (CNAG), Barcelona, Spain
| | - Berta Romero-Grimaldo
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), European Association for the Study of the Liver (EASL)–CLIF Consortium, and Grifols Chair, Barcelona, Spain
- Hospital Clínic-IDIBAPS, Barcelona, Spain
- CIBER of Hepatic and Digestive Diseases (CIBERehd); Barcelona, Spain
| | - Xavi Marcos-Fa
- Translational Clinical Research Program, Institute “Hospital del Mar” for Medical Investigations (IMIM), Barcelona, Spain
| | - Emma Giarracco
- Translational Clinical Research Program, Institute “Hospital del Mar” for Medical Investigations (IMIM), Barcelona, Spain
| | - Emmanuel Weiss
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), European Association for the Study of the Liver (EASL)–CLIF Consortium, and Grifols Chair, Barcelona, Spain
- Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Cité, Centre de Recherche sur l’Inflammation (CRI), Paris, France
- Assistance Publique–Hôpitaux de Paris (AP-HP), Hôpital Beaujon, Département d’Anesthésie et de Réanimation, DMU Parabol, Clichy, France
| | - Jonel Trebicka
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), European Association for the Study of the Liver (EASL)–CLIF Consortium, and Grifols Chair, Barcelona, Spain
- Department of Internal Medicine B, University of Münster, Münster, Germany
| | - Inmaculada Hernàndez
- Universitat de Barcelona, Barcelona, Spain
- Centre Nacional d’Anàlisi Genòmica (CNAG), Barcelona, Spain
- Institute for Research in Biomedicine (IRB), Barcelona, Spain
| | - Javier Fernandez
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), European Association for the Study of the Liver (EASL)–CLIF Consortium, and Grifols Chair, Barcelona, Spain
- Hospital Clínic-IDIBAPS, Barcelona, Spain
| | - Mireia Casulleras
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), European Association for the Study of the Liver (EASL)–CLIF Consortium, and Grifols Chair, Barcelona, Spain
- Hospital Clínic-IDIBAPS, Barcelona, Spain
| | - Cristina López-Vicario
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), European Association for the Study of the Liver (EASL)–CLIF Consortium, and Grifols Chair, Barcelona, Spain
- Hospital Clínic-IDIBAPS, Barcelona, Spain
- CIBER of Hepatic and Digestive Diseases (CIBERehd); Barcelona, Spain
| | - Sinan Muldur
- Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Shriners Burns Hospital, Harvard Medical School, Boston, MA, USA
| | - Alex Hopke
- Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Shriners Burns Hospital, Harvard Medical School, Boston, MA, USA
| | | | - Ana M. Aransay
- CIBER of Hepatic and Digestive Diseases (CIBERehd); Barcelona, Spain
- Center for Cooperative Research in Biosciences (CIC bioGUNE), Parque Tecnológico de Bizkaia, Derio, Spain
| | - Domenica Marchese
- Universitat de Barcelona, Barcelona, Spain
- Centre Nacional d’Anàlisi Genòmica (CNAG), Barcelona, Spain
| | - Mauro Bernardi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Rajiv Jalan
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), European Association for the Study of the Liver (EASL)–CLIF Consortium, and Grifols Chair, Barcelona, Spain
- Liver Failure Group, Institute for Liver Disease Health, University College London, Royal Free Hospital, London, UK
| | - Paolo Angeli
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), European Association for the Study of the Liver (EASL)–CLIF Consortium, and Grifols Chair, Barcelona, Spain
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine – DIMED, University of Padova, Padova, Italy
| | - Giuliana Magri
- Immunology Unit, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
| | - Andrea Cerutti
- Translational Clinical Research Program, Institute “Hospital del Mar” for Medical Investigations (IMIM), Barcelona, Spain
- Catalan Institute for Research and Advanced Studies (ICREA); Barcelona, Spain
| | - Daniel Irimia
- Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Shriners Burns Hospital, Harvard Medical School, Boston, MA, USA
| | - Holger Heyn
- Universitat de Barcelona, Barcelona, Spain
- Centre Nacional d’Anàlisi Genòmica (CNAG), Barcelona, Spain
| | - Vicente Arroyo
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), European Association for the Study of the Liver (EASL)–CLIF Consortium, and Grifols Chair, Barcelona, Spain
| | - Richard Moreau
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), European Association for the Study of the Liver (EASL)–CLIF Consortium, and Grifols Chair, Barcelona, Spain
- Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Cité, Centre de Recherche sur l’Inflammation (CRI), Paris, France
- Assistance Publique – Hôpitaux de Paris (AP-HP), Hôpital Beaujon, Service d’Hépatologie, Clichy, France
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30
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Zhang D, Shi C, Wang Y, Guo J, Gong Z. Metabolic Dysregulation and Metabolite Imbalances in Acute-on-chronic Liver Failure: Impact on Immune Status. J Clin Transl Hepatol 2024; 12:865-877. [PMID: 39440217 PMCID: PMC11491507 DOI: 10.14218/jcth.2024.00203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 08/26/2024] [Accepted: 09/04/2024] [Indexed: 10/25/2024] Open
Abstract
Liver failure encompasses a range of severe clinical syndromes resulting from the deterioration of liver function, triggered by factors both within and outside the liver. While the definition of acute-on-chronic liver failure (ACLF) may vary by region, it is universally recognized for its association with multiorgan failure, a robust inflammatory response, and high short-term mortality rates. Recent advances in metabolomics have provided insights into energy metabolism and metabolite alterations specific to ACLF. Additionally, immunometabolism is increasingly acknowledged as a pivotal mechanism in regulating immune cell functions. Therefore, understanding the energy metabolism pathways involved in ACLF and investigating how metabolite imbalances affect immune cell functionality are crucial for developing effective treatment strategies for ACLF. This review methodically examined the immune and metabolic states of ACLF patients and elucidated how alterations in metabolites impact immune functions, offering novel perspectives for immune regulation and therapeutic management of liver failure.
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Affiliation(s)
- Danmei Zhang
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Chunxia Shi
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yukun Wang
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Jin Guo
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Zuojiong Gong
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
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31
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Wu J, Yu J, Li H, Wang Y, Xu R. Fatal invasive Aspergillus infection in an elderly patient with hepatitis E: A case report and literature review. Medicine (Baltimore) 2024; 103:e40103. [PMID: 39470540 PMCID: PMC11521067 DOI: 10.1097/md.0000000000040103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 09/23/2024] [Accepted: 09/27/2024] [Indexed: 10/30/2024] Open
Abstract
RATIONALE Elderly patients with acute liver failure are highly susceptible to severe complications, such as invasive fungal infections, due to weakened immune systems and altered gut microbiota. A thorough understanding of liver failure and opportunistic infections is crucial for effective management. PATIENT CONCERNS An 84-year-old male with acute liver failure from hepatitis E experienced worsening jaundice despite standard treatments. He also developed respiratory symptoms, including blood-streaked sputum, raising concerns about a potential fungal infection. DIAGNOSES The patient was diagnosed with acute liver failure secondary to hepatitis E and an invasive fungal infection caused by Aspergillus fumigatus. Initial treatments included artificial liver plasma exchange and antifungal prophylaxis. Further diagnostics, including bronchoscopy and next-generation sequencing of alveolar lavage fluid, confirmed the Aspergillus infection. LESSONS Elderly liver failure patients are particularly prone to opportunistic infections, underscoring the need for vigilant monitoring and early intervention. Despite aggressive treatments, including antifungal therapy and artificial liver support, prognosis remains poor, highlighting the importance of prompt diagnosis and comprehensive management to enhance patient outcomes.
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Affiliation(s)
- Junjun Wu
- Department of Gastroenterology, Hangzhou Third People’s Hospital, Hangzhou, China
| | - Jin Yu
- Department of Gastroenterology, Hangzhou Third People’s Hospital, Hangzhou, China
| | - Huaming Li
- Department of Gastroenterology, Hangzhou Third People’s Hospital, Hangzhou, China
| | - Yufang Wang
- Department of Gastroenterology, Hangzhou Third People’s Hospital, Hangzhou, China
| | - Rong Xu
- Department of Gastroenterology, Hangzhou Third People’s Hospital, Hangzhou, China
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32
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Rodríguez-Negrete EV, Gálvez-Martínez M, Sánchez-Reyes K, Fajardo-Felix CF, Pérez-Reséndiz KE, Madrigal-Santillán EO, Morales-González Á, Morales-González JA. Liver Cirrhosis: The Immunocompromised State. J Clin Med 2024; 13:5582. [PMID: 39337069 PMCID: PMC11432654 DOI: 10.3390/jcm13185582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 09/11/2024] [Accepted: 09/17/2024] [Indexed: 09/30/2024] Open
Abstract
Systemic inflammation and immunodeficiency are important components of cirrhosis-associated immune dysfunction (CAID), the severity of which is dynamic, progressive, and associated with the greater deterioration of liver function. Two inflammation phenotypes have been described: low-grade and high-grade systemic inflammation. Both of these phenotypes are related to liver cirrhosis function; thus, high-grade inflammation is correlated with the severity of hepatic insufficiency, bacterial translocation, and organic insufficiency, with which the risk of infections increases and the prognosis worsens. Bacterial translocation (BT) plays a relevant role in persistent systemic inflammation in patients with cirrhosis, and the prophylactic employment of antibiotics is useful for reducing events of infection and mortality.
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Affiliation(s)
- Elda Victoria Rodríguez-Negrete
- Servicio de Gastroenterología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Ciudad de México 06720, Mexico
- Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico
| | - Marisol Gálvez-Martínez
- Servicio de Gastroenterología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Ciudad de México 06720, Mexico
| | - Karina Sánchez-Reyes
- Servicio de Cirugía General, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Ciudad de México 06720, Mexico
| | - Carlos Fernando Fajardo-Felix
- Servicio de Gastroenterología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Ciudad de México 06720, Mexico
| | - Karla Erika Pérez-Reséndiz
- Servicio de Gastroenterología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Ciudad de México 06720, Mexico
| | | | - Ángel Morales-González
- Escuela Superior de Cómputo, Instituto Politécnico Nacional, Unidad Profesional "A. López Mateos", Ciudad de México 07738, Mexico
| | - José Antonio Morales-González
- Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico
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33
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Dibos M, Mayr U, Triebelhorn J, Schmid RM, Lahmer T. [Infections and liver cirrhosis]. Med Klin Intensivmed Notfmed 2024; 119:465-469. [PMID: 39120610 DOI: 10.1007/s00063-024-01168-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 07/10/2024] [Accepted: 07/10/2024] [Indexed: 08/10/2024]
Abstract
End-stage liver disease is a life-threatening clinical syndrome combined with a state of immune dysfunction. In this constellation patients are prone to bacterial, fungal and viral infections associated with markedly increased morbidity and mortality rates. Bacterial infections are the most prevalent kind of infection in patients with end-stage liver disease accounting for nearly 30%. The evolving rates of multidrug resistant organisms present enormous challenges in treatment strategies. Therefore, the urgent needs for prevention, early detection strategies and widespread treatment options are a necessity to handle the rising incidence of infection complications in end-stage liver disease.
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Affiliation(s)
| | | | | | | | - Tobias Lahmer
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675, München, Deutschland.
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34
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Kaya E, Nekarda P, Traut I, Aurich P, Canbay A, Katsounas A. [When should a liver disease patient be admitted to the intensive care unit?]. Med Klin Intensivmed Notfmed 2024; 119:470-477. [PMID: 39017943 DOI: 10.1007/s00063-024-01160-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 05/27/2024] [Accepted: 06/04/2024] [Indexed: 07/18/2024]
Abstract
Liver diseases are a significant global cause of morbidity and mortality. Liver cirrhosis can result in severe complications such as bleeding, hepatic encephalopathy (HE), and infections. Implementing a clear strategy for intensive care unit (ICU) admission management improves patient outcomes. Hemodynamically significant esophageal/gastric variceal bleeding (E/GVB) and grade 4 HE, when accompanied by the need for renal replacement therapy (RRT), are definitive indications for ICU admission. E/GVB, spontaneous bacterial peritonitis (SBP), and infections with multidrug-resistant organisms (MDRO) require close and stringent critical assessment. Patients with severe hepatorenal syndrome (HRS) or respiratory failure have increased baseline mortality and most likely benefit from early ICU treatment. Rapid identification of sepsis in patients with liver cirrhosis is a crucial criterion for ICU admission. Prioritizing cases based on mortality risk and clinical urgency enables efficient resource utilization and optimizes patient management. In addition, "Liver Units" provide an intermediate care (IMC) level for patients with liver diseases who require close monitoring but do not need immediate intensive care.
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Affiliation(s)
- Eda Kaya
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Ruhr-Universität Bochum, In der Schornau 23-25, 44892, Bochum, Deutschland
| | - Patrick Nekarda
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Ruhr-Universität Bochum, In der Schornau 23-25, 44892, Bochum, Deutschland
| | - Isabella Traut
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Ruhr-Universität Bochum, In der Schornau 23-25, 44892, Bochum, Deutschland
| | - Philipp Aurich
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Ruhr-Universität Bochum, In der Schornau 23-25, 44892, Bochum, Deutschland
| | - Ali Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Ruhr-Universität Bochum, In der Schornau 23-25, 44892, Bochum, Deutschland
| | - Antonios Katsounas
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Ruhr-Universität Bochum, In der Schornau 23-25, 44892, Bochum, Deutschland.
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35
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. S2k-Leitlinie Lebertransplantation der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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Yuan M, Han N, Lv D, Huang W, Zhou M, Yan L, Tang H. Invasive Pulmonary Aspergillosis in Patients with HBV-Related Acute on Chronic Liver Failure. J Fungi (Basel) 2024; 10:571. [PMID: 39194897 DOI: 10.3390/jof10080571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 08/07/2024] [Accepted: 08/08/2024] [Indexed: 08/29/2024] Open
Abstract
BACKGROUND We aim to investigate the characteristics of invasive pulmonary aspergillosis (IPA) in patients with HBV-related acute on chronic liver failure (HBV-ACLF). METHODS A total of 44 patients with probable IPA were selected as the case group, and another 88 patients without lung infections were chosen as the control group. RESULTS HBV-ACLF patients with probable IPA had more significant 90-day mortality (38.6% vs. 15.9%, p = 0.0022) than those without. The white blood cell (WBC) count was the independent factor attributed to the IPA development [odds ratio (OR) 1.468, p = 0.027]. Respiratory failure was associated with the mortality of HBV-ACLF patients with IPA [OR 26, p = 0.000]. Twenty-seven patients received voriconazole or voriconazole plus as an antifungal treatment. Plasma voriconazole concentration measurements were performed as therapeutic drug monitoring in 55.6% (15/27) of the patients. The drug concentrations exceeded the safe range with a reduced dosage. CONCLUSIONS The WBC count might be used to monitor patients' progress with HBV-ACLF and IPA. The presence of IPA increases the 90-day mortality of HBV-ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients, and voriconazole should be assessed by closely monitoring blood levels.
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Affiliation(s)
- Man Yuan
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
| | - Ning Han
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
| | - Duoduo Lv
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
| | - Wei Huang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
| | - Mengjie Zhou
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Libo Yan
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
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Li S, Zhang Y, Lin Y, Zheng L, Fang K, Wu J. Development and validation of prediction models for nosocomial infection and prognosis in hospitalized patients with cirrhosis. Antimicrob Resist Infect Control 2024; 13:85. [PMID: 39113159 PMCID: PMC11304655 DOI: 10.1186/s13756-024-01444-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 07/27/2024] [Indexed: 08/10/2024] Open
Abstract
BACKGROUND Nosocomial infections (NIs) frequently occur and adversely impact prognosis for hospitalized patients with cirrhosis. This study aims to develop and validate two machine learning models for NIs and in-hospital mortality risk prediction. METHODS The Prediction of Nosocomial Infection and Prognosis in Cirrhotic patients (PIPC) study included hospitalized patients with cirrhosis at the Qingchun Campus of the First Affiliated Hospital of Zhejiang University. We then assessed several machine learning algorithms to construct predictive models for NIs and prognosis. We validated the best-performing models with bootstrapping techniques and an external validation dataset. The accuracy of the predictions was evaluated through sensitivity, specificity, predictive values, and likelihood ratios, while predictive robustness was examined through subgroup analyses and comparisons between models. RESULTS We enrolled 1,297 patients into derivation cohort and 496 patients into external validation cohort. Among the six algorithms assessed, the Random Forest algorithm performed best. For NIs, the PIPC-NI model achieved an area under the curve (AUC) of 0.784 (95% confidence interval [CI] 0.741-0.826), a sensitivity of 0.712, and a specificity of 0.702. For in-hospital mortality, the PIPC- mortality model achieved an AUC of 0.793 (95% CI 0.749-0.836), a sensitivity of 0.769, and a specificity of 0.701. Moreover, our PIPC models demonstrated superior predictive performance compared to the existing MELD, MELD-Na, and Child-Pugh scores. CONCLUSIONS The PIPC models showed good predictive power and may facilitate healthcare providers in easily assessing the risk of NIs and prognosis among hospitalized patients with cirrhosis.
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Affiliation(s)
- Shuwen Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Yu Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Yushi Lin
- Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Luyan Zheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Kailu Fang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Jie Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
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Gananandan K, Wiese S, Møller S, Mookerjee RP. Cardiac dysfunction in patients with cirrhosis and acute decompensation. Liver Int 2024; 44:1832-1841. [PMID: 38712826 DOI: 10.1111/liv.15896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 02/25/2024] [Accepted: 03/04/2024] [Indexed: 05/08/2024]
Abstract
The prevalence of cirrhotic cardiomyopathy (CCM) has been reported as high as 60%-70% in patients with liver cirrhosis and is associated with various negative outcomes. There has been a growing understanding of CCM over recent years. Indeed, the development of imaging techniques has enabled new diagnostic criteria to be proposed by the Cirrhotic Cardiomyopathy Consortium. However, important unanswered questions remain over pathophysiological mechanisms, optimal diagnostic modalities and potential treatment options. While there has been an increasing volume of literature evaluating CCM, there is a lack of clarity on its implications in acute decompensation, acute-on-chronic liver failure and following interventions such as transjugular intrahepatic portosystemic shunt insertion and liver transplantation. This review aims to summarise the literature in these challenging domains and suggest where future research should focus. We conclude that systemic inflammation and structural myocardial changes are likely to be crucial in the pathophysiology of the disease, but the relative contribution of different components remains elusive. Furthermore, future studies need to use standardised diagnostic criteria for CCM as well as incorporate newer imaging techniques assessing both myocardial structure and function. Finally, while specific treatments are currently lacking, therapeutics targeting systemic inflammation, microbial dysbiosis and bacterial translocation are promising targets and warrant further research.
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Affiliation(s)
- Kohilan Gananandan
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, London, UK
| | - Signe Wiese
- Centre of Functional Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, University of Copenhagen, Copenhagen, Denmark
- Gastroenterology Unit, Medical Division, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Søren Møller
- Centre of Functional Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Rajeshwar P Mookerjee
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, London, UK
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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Incicco S, Angeli P, Piano S. Infectious Complications of Portal Hypertension. Clin Liver Dis 2024; 28:525-539. [PMID: 38945641 DOI: 10.1016/j.cld.2024.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
Patients with cirrhosis and clinically significant portal hypertension are at high risk of developing bacterial infections (BIs) that are the most common trigger of acute decompensation and acute-on-chronic liver failure. Furthermore, after decompensation, the risk of developing BIs further increases in an ominous vicious circle. BIs may be subtle, and they should be ruled out in all patients at admission and in case of deterioration. Timely administration of adequate empirical antibiotics is the cornerstone of treatment. Herein, we reviewed current evidences about pathogenesis, clinical implications and management of BIs in patients with cirrhosis and portal hypertension.
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Affiliation(s)
- Simone Incicco
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University and Hospital of Padova, via Giustiniani 2, Padova 35100, Italy
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University and Hospital of Padova, via Giustiniani 2, Padova 35100, Italy
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine (DIMED), University and Hospital of Padova, via Giustiniani 2, Padova 35100, Italy.
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Piano S, Bunchorntavakul C, Marciano S, Rajender Reddy K. Infections in cirrhosis. Lancet Gastroenterol Hepatol 2024; 9:745-757. [PMID: 38754453 DOI: 10.1016/s2468-1253(24)00078-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 03/04/2024] [Accepted: 03/04/2024] [Indexed: 05/18/2024]
Abstract
Cirrhosis is an immune dysfunction state, and as such, patients with cirrhosis are susceptible to bacterial, fungal, and viral infections. Because of infection, these patients have a propensity to develop multiorgan failure, which is associated with high mortality. Bacterial infections are the most prevalent type of infection in patients with cirrhosis, with the prevalence of bacterial infections in patients admitted for an acute decompensating event ranging from 24% to 29%. Together with invasive fungal infections, bacterial infections are the most severe. Multidrug-resistant organisms have been evolving at a rapid and alarming rate around the world, which presents enormous challenges. The development of effective measures for the prevention, early detection, and treatment of infections in patients with cirrhosis is challenging, given the rising incidence of infections in this patient population.
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Affiliation(s)
- Salvatore Piano
- Unit of Internal Medicine and Hepatology, Department of Medicine, University and Hospital of Padova, Padova, Italy
| | | | - Sebastian Marciano
- Department of Clinical Investigation, Italian Hospital, Buenos Aires, Argentina
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA.
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Fernández J, Blasi A, Hidalgo E, Karvellas CJ. Bridging the critically ill patient with acute to chronic liver failure to liver transplantation. Am J Transplant 2024; 24:1348-1361. [PMID: 38548058 DOI: 10.1016/j.ajt.2024.03.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 03/16/2024] [Accepted: 03/18/2024] [Indexed: 04/14/2024]
Abstract
Liver transplantation (LT) has emerged as an effective therapy for severe forms of acute-on-chronic liver failure (ACLF), an entity characterized by the development of multiorgan failure and high short-term mortality. The aim of critical care management of ACLF patients is to rapidly treat precipitating events and aggressively support failing organs to ensure that patients may successfully undergo LT or, less frequently, recover. Malnutrition and sarcopenia are frequently present, adversely impacting the prognosis of these patients. Management of critical care patients with ACLF is complex and requires the participation of different specialties. Once the patient is stabilized, a rapid evaluation for salvage LT should be performed because the time window for LT is often narrow. The development of sepsis and prolonged organ support may preclude LT or diminish its chances of success. The current review describes strategies to bridge severe ACLF patients to LT, highlights the minimal evaluation required for listing and the currently suggested contraindications to proceed with LT, and addresses different aspects of management during the perioperative and early posttransplant period.
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Affiliation(s)
- Javier Fernández
- Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS and CIBERehd, Spain; EF Clif, EASL-CLIF Consortium, Barcelona, Spain.
| | - Annabel Blasi
- Anesthesiology Department, Hospital Clínic, and University of Barcelona, Spain
| | - Ernest Hidalgo
- Hepatolobiliary Surgery Department, Hospital Vall d'Hebron, Barcelona, Spain
| | - Constantine J Karvellas
- Department of Critical Care Medicine, University of Alberta, Edmonton, Canada; Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada
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Xu Z, Zhang X, Chen J, Shi Y, Ji S. Bacterial Infections in Acute-on-chronic Liver Failure: Epidemiology, Diagnosis, Pathogenesis, and Management. J Clin Transl Hepatol 2024; 12:667-676. [PMID: 38993512 PMCID: PMC11233977 DOI: 10.14218/jcth.2024.00137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 05/05/2024] [Accepted: 05/27/2024] [Indexed: 07/13/2024] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a distinct condition characterized by the abrupt exacerbation of pre-existing chronic liver disease, often leading to multi-organ failures and significant short-term mortalities. Bacterial infection is one of the most frequent triggers for ACLF and a common complication following its onset. The impact of bacterial infections on the clinical course and outcome of ACLF underscores their critical role in the pathogenesis of systemic inflammation and organ failures. In addition, the evolving epidemiology and increasing prevalence of multidrug-resistant bacteria in cirrhosis and ACLF highlight the importance of appropriate empirical antibiotic use, as well as accurate and prompt microbiological diagnosis. This review provided an update on recent advances in the epidemiology, diagnosis, pathogenesis, and management of bacterial infections in ACLF.
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Affiliation(s)
- Zhaoyu Xu
- China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Xiuding Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Jiyang Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Yu Shi
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Shangwei Ji
- Department of Infectious Diseases, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
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Song DS, Kim HY, Jung YK, Kim TH, Yim HJ, Yoon EL, Suk KT, Yoo JJ, Kim SG, Kim MY, Chang Y, Jeong SW, Jang JY, Kim SE, Kim JH, Park JG, Kim W, Yang JM, Kim DJ, Choudhury AK, Arora V, Sarin SK. Dynamic analysis of acute deterioration in chronic liver disease patients using modified quick sequential organ failure assessment. Clin Mol Hepatol 2024; 30:388-405. [PMID: 38600873 PMCID: PMC11261223 DOI: 10.3350/cmh.2023.0563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 03/23/2024] [Accepted: 04/09/2024] [Indexed: 04/12/2024] Open
Abstract
BACKGROUND/AIMS Quick sequential organ failure assessment (qSOFA) is believed to identify patients at risk of poor outcomes in those with suspected infection. We aimed to evaluate the ability of modified qSOFA (m-qSOFA) to identify high-risk patients among those with acutely deteriorated chronic liver disease (CLD), especially those with acute-onchronic liver failure (ACLF). METHODS We used data from both the Korean Acute-on-Chronic Liver Failure (KACLiF) and the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) cohorts. qSOFA was modified by replacing the Glasgow Coma Scale with hepatic encephalopathy, and an m-qSOFA ≥2 was considered high. RESULTS Patients with high m-qSOFA had a significantly lower 1-month transplant-free survival (TFS) in both cohorts and higher organ failure development in KACLiF than those with low m-qSOFA (Ps<0.05). Subgroup analysis by ACLF showed that patients with high m-qSOFA had lower TFS than those with low m-qSOFA. m-qSOFA was an independent prognostic factor (hazard ratios, HR=2.604, 95% confidence interval, CI 1.353-5.013, P=0.004 in KACLiF and HR=1.904, 95% CI 1.484- 2.442, P<0.001 in AARC). The patients with low m-qSOFA at baseline but high m-qSOFA on day 7 had a significantly lower 1-month TFS than those with high m-qSOFA at baseline but low m-qSOFA on day 7 (52.6% vs. 89.4%, P<0.001 in KACLiF and 26.9% vs. 61.5%, P<0.001 in AARC). CONCLUSION Baseline and dynamic changes in m-qSOFA may identify patients with a high risk of developing organ failure and short-term mortality among CLD patients with acute deterioration.
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Affiliation(s)
- Do Seon Song
- Department of Internal Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Hee Yeon Kim
- Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Young Kul Jung
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Tae Hyung Kim
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Hyung Joon Yim
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
| | - Eileen L Yoon
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Ki Tae Suk
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Jeong-ju Yoo
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Young Chang
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Soung Won Jeong
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Jae Young Jang
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Sung-Eun Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Jung-Hee Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Jung Gil Park
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Won Kim
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
| | - Jin Mo Yang
- Department of Internal Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Korean Acute-on-Chronic Liver Failure (KACLiF) study group
- Department of Internal Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Seoul, Korea
- Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Vinod Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - APASL ACLF Research Consortium (AARC) for APASL ACLF working party
- Department of Internal Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Seoul, Korea
- Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Wei H, Yi K, Li F, Li D, Yang J, Shi R, Jin Y, Wang H, Ding J, Tao Y, Li M. Multimodal Tetrahedral DNA Nanoplatform for Surprisingly Rapid and Significant Treatment of Acute Liver Failure. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2305826. [PMID: 37801371 DOI: 10.1002/adma.202305826] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 09/07/2023] [Indexed: 10/08/2023]
Abstract
Acute liver failure (ALF) is a life-threatening disease associated with the rapid development of inflammatory storms, level elevation of reactive oxygen species (ROS), and hepatocyte necrosis, which results in high short-term mortality. Except for liver transplantation, no effective strategies are available for ALF therapy due to the rapid disease progression and narrow window of therapeutic time. Therefore, there is an urgent demand to explore the fast and effective modalities for ALF treatment. Herein, a multifunctional tetrahedral DNA nanoplatform (TDN) is constructed by incorporating tumor necrosis factor-α siRNA (siTNF-α) through DNA hybridization and antioxidant manganese porphyrin (MnP4) via π-π stacking interaction with G-quadruplex (G4) for surprisingly rapid and significant ALF therapy. TDN-siTNF-α/-G4-MnP4 silences TNF-α of macrophages by siTNF-α and polarizes them to the anti-inflammatory M2 phenotype, providing appropriate microenvironments for hepatocyte viability. Additionally, TDN-siTNF-α/-G4-MnP4 scavenges intracellular ROS by MnP4, protecting hepatocytes from oxidative-stress-associated cell death. Furthermore, TDN itself promotes hepatocyte proliferation by modulating the cell cycle. TDN-siTNF-α/-G4-MnP4 shows almost complete liver accumulation after intravenous injection and exhibits excellent therapeutic efficacy of ALF within 2 h. The multifunctional DNA nanoformulation provides an effective strategy for rapid ALF therapy, expanding its application for innovative treatments of liver diseases.
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Affiliation(s)
- Hongyan Wei
- Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, P. R. China
- Guangdong Provincial Key Laboratory of Liver Disease, 600 Tianhe Road, Guangzhou, 510630, P. R. China
- Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children, 120 Longshan Road, Chongqing, 401147, P. R. China
| | - Ke Yi
- Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, P. R. China
| | - Fenfang Li
- Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, P. R. China
| | - Di Li
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, P. R. China
| | - Jiazhen Yang
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, P. R. China
| | - Run Shi
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, P. R. China
| | - Yuanyuan Jin
- Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, P. R. China
| | - Haixia Wang
- Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, P. R. China
| | - Jianxun Ding
- Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, P. R. China
- State Key Laboratory of Molecular Engineering of Polymers, Fudan University, 220 Handan Road, Shanghai, 200433, P. R. China
| | - Yu Tao
- Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, P. R. China
- Guangdong Provincial Key Laboratory of Liver Disease, 600 Tianhe Road, Guangzhou, 510630, P. R. China
| | - Mingqiang Li
- Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, P. R. China
- Guangdong Provincial Key Laboratory of Liver Disease, 600 Tianhe Road, Guangzhou, 510630, P. R. China
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Karvellas CJ, Bajaj JS, Kamath PS, Napolitano L, O'Leary JG, Solà E, Subramanian R, Wong F, Asrani SK. AASLD Practice Guidance on Acute-on-chronic liver failure and the management of critically ill patients with cirrhosis. Hepatology 2024; 79:1463-1502. [PMID: 37939273 DOI: 10.1097/hep.0000000000000671] [Citation(s) in RCA: 23] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 11/01/2023] [Indexed: 11/10/2023]
Affiliation(s)
- Constantine J Karvellas
- Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, Edmonton, Canada
| | - Jasmohan S Bajaj
- Virginia Commonwealth University, Central Virginia Veterans Healthcare System, Richmond, Virginia, USA
| | - Patrick S Kamath
- Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA
| | | | - Jacqueline G O'Leary
- Department of Medicine, Dallas Veterans Medical Center, University of Texas Southwestern Medical Center Dallas, Texas, USA
| | - Elsa Solà
- Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA
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Idalsoaga F, Díaz LA, Fuentes-López E, Ayares G, Valenzuela F, Meza V, Manzur F, Sotomayor J, Rodriguez H, Chianale F, Villagrán S, Schalper M, Villafranca P, Veliz MJ, Uribe P, Puebla M, Bustamante P, Aguirre H, Busquets J, Roblero JP, Mezzano G, Hernandez-Tejero M, Arrese M, Arab JP. Active alcohol consumption is associated with acute-on-chronic liver failure in Hispanic patients. GASTROENTEROLOGIA Y HEPATOLOGIA 2024; 47:562-573. [PMID: 37778718 DOI: 10.1016/j.gastrohep.2023.09.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 09/16/2023] [Accepted: 09/18/2023] [Indexed: 10/03/2023]
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is a severe clinical entity associated with elevated short-term mortality. We aimed to characterize patients with decompensated cirrhosis according to presence of ACLF, their association with active alcohol intake, and long-term survival in Latin America. METHODS Retrospective cohort study of decompensated cirrhotic in three Chilean university centers (2017-2019). ACLF was diagnosed according EASL-CLIF criteria. We assessed survival using competing-risk and time-to-event analyses. We evaluated the time to death using accelerated failure time (AFT) models. RESULTS We included 320 patients, median age of 65.3±11.7 years old, and 48.4% were women. 92 (28.7%) patients met ACLF criteria (ACLF-1: 29.3%, ACLF-2: 27.1%, and ACLF-3: 43.4%). The most common precipitants were infections (39.1%), and the leading organ failure was kidney (59.8%). Active alcohol consumption was frequent (27.7%), even in patients with a prior diagnosis of non-alcoholic fatty liver disease (NAFLD) (16.2%). Ninety-two (28.7%) patients had ACLF (ACLF-1: 8.4%, ACLF-2: 7.8%, and ACLF-3: 12.5%). ACLF patients had a higher MELD-Na score at admission (27 [22-31] versus 16 [12-21], p<0.0001), a higher frequency of alcohol-associated liver disease (36.7% versus 24.9%, p=0.039), and a more frequent active alcohol intake (37.2% versus 23.8%, p=0.019). In a multivariate model, ACLF was associated with higher mortality (subdistribution hazard ratio 1.735, 95%CI: 1.153-2.609; p<0.008). In the AFT models, the presence of ACLF during hospitalization correlated with a shorter time to death: ACLF-1 shortens the time to death by 4.7 times (time ratio [TR] 0.214, 95%CI: 0.075-0.615; p<0.004), ACLF-2 by 4.4 times (TR 0.224, 95%CI: 0.070-0.713; p<0.011), and ACLF-3 by 37 times (TR 0.027, 95%CI: 0.006-0.129; p<0.001). CONCLUSIONS Patients with decompensated cirrhosis and ACLF exhibited a high frequency ofactive alcohol consumption. Patients with ACLF showed higher mortality and shorter time todeath than those without ACLF.
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Affiliation(s)
- Francisco Idalsoaga
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Luis Antonio Díaz
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Eduardo Fuentes-López
- Departamento de Ciencias de la Salud, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Gustavo Ayares
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Francisco Valenzuela
- Departamento de Medicina Interna, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Victor Meza
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Franco Manzur
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Joaquín Sotomayor
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Hernán Rodriguez
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Franco Chianale
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Sofía Villagrán
- Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | | | | | | | - Paz Uribe
- Escuela de Medicina, Universidad de Chile, Santiago, Chile
| | | | - Pablo Bustamante
- Departamento de Medicina, Sección Gastroenterología, Hospital Clínico Universidad de Chile, Universidad de Chile, Santiago, Chile
| | - Herman Aguirre
- Departamento de Medicina, Sección Gastroenterología, Hospital Clínico Universidad de Chile, Universidad de Chile, Santiago, Chile
| | - Javiera Busquets
- Departamento de Medicina, Sección Gastroenterología, Hospital Clínico Universidad de Chile, Universidad de Chile, Santiago, Chile
| | - Juan Pablo Roblero
- Departamento de Medicina, Sección Gastroenterología, Hospital Clínico Universidad de Chile, Universidad de Chile, Santiago, Chile
| | - Gabriel Mezzano
- Sección de Gastroenterología, Hospital del Salvador, Santiago, Chile; Centro de Enfermedades Digestivas, Universidad de los Andes, Santiago, Chile
| | - Maria Hernandez-Tejero
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Marco Arrese
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Juan Pablo Arab
- Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Schulich School of Medicine, Western University, London, Ontario, Canada.
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Batra N, Gaidhane SA, Kumar S, Acharya S. Outcome Predictors of Acute-on-Chronic Liver Failure: A Narrative Review. Cureus 2024; 16:e61655. [PMID: 38966452 PMCID: PMC11223737 DOI: 10.7759/cureus.61655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Accepted: 06/04/2024] [Indexed: 07/06/2024] Open
Abstract
Complications of acute-on-chronic liver failure (ACLF) include increased short-term mortality. Extrahepatic organ failures result from chronic liver disease and acute hepatic injury. This combination characterizes end-stage liver disease. Its rapid progression makes it challenging for hepatologists and intensivists to treat. The varied definitions of this condition lead to varied clinical presentations. Hepatic or extrahepatic failures are more prevalent in chronic hepatitis B or cirrhosis patients who receive an additional injury. Numerous intensity parameters and prognosis ratings, including those for hepatitis B virus (HBV), have been developed and verified for various patients and causes of the disease. Liver regeneration, liver transplantation (LT), or antiviral therapy for HBV-related ACLF are the main treatment aims for various organ failures. LT is the best treatment for HBV-ACLF. In some HBV-related ACLF patients, nucleos(t)ide analogs and artificial liver assistance may enhance survival. Combining epidemiological and clinical studies, this review updates our understanding of HBV-ACLF's definition, diagnosis, epidemiology, etiology, therapy, and prognosis.
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Affiliation(s)
- Nitish Batra
- Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Shilpa A Gaidhane
- Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Sunil Kumar
- Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Sourya Acharya
- Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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Trad N, Mohamed G, Bizid S, Abdallah HB, Bouali R, Abdelli MN. Clinical impact of multidrug-resistant bacterial infections in patients with cirrhosis. Future Sci OA 2024; 10:FSO945. [PMID: 38813115 PMCID: PMC11131343 DOI: 10.2144/fsoa-2023-0160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 11/17/2023] [Indexed: 05/31/2024] Open
Abstract
Aim: Recently, the emergency of multidrug-resistant organisms (MDRO) has complicated the management of bacterial infections (BI) in cirrhosis. We aimed to assess their clinical impact on patients with decompensated cirrhosis. Methods: A retrospective study included consecutive cirrhotic patients hospitalized for acute decompensation (AD) between January 2010 and December 2019. Results: A total of 518 AD admissions in 219 patients were included, with 260 BI episodes (50.2%). MDRO prevalence was 38.2% of the total isolates. Recent antibiotic use (OR = 4.91), nosocomial infection (OR = 2.95), and healthcare-associated infection (OR = 3.45) were their main risk factors. MDROs were associated with empiric treatment failure (OR = 23.42), a higher prevalence of sepsis (OR = 4.93), ACLF (OR = 3.42) and mortality. Conclusion: The clinical impact of MDROs was pejorative, with an increased risk of empiric treatment failure, organ failure and death.
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Affiliation(s)
- Nouha Trad
- Gastroenterology department, Principal Military Hospital of Instruction of Tunis, Faculty of medicine of Tunis, University Tunis El Manar Tunis, Tunisia
| | - Ghanem Mohamed
- Gastroenterology department, Principal Military Hospital of Instruction of Tunis, Faculty of medicine of Tunis, University Tunis El Manar Tunis, Tunisia
| | - Sondes Bizid
- Gastroenterology department, Principal Military Hospital of Instruction of Tunis, Faculty of medicine of Tunis, University Tunis El Manar Tunis, Tunisia
| | - Hatem Ben Abdallah
- Gastroenterology department, Principal Military Hospital of Instruction of Tunis, Faculty of medicine of Tunis, University Tunis El Manar Tunis, Tunisia
| | - Riadh Bouali
- Gastroenterology department, Principal Military Hospital of Instruction of Tunis, Faculty of medicine of Tunis, University Tunis El Manar Tunis, Tunisia
| | - Mohamed Nabil Abdelli
- Gastroenterology department, Principal Military Hospital of Instruction of Tunis, Faculty of medicine of Tunis, University Tunis El Manar Tunis, Tunisia
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Artru F, McPhail MJ. Immunopathogenesis of acute on chronic liver failure. Am J Transplant 2024; 24:724-732. [PMID: 38346497 DOI: 10.1016/j.ajt.2024.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Revised: 01/13/2024] [Accepted: 02/01/2024] [Indexed: 02/23/2024]
Abstract
Acute-on-chronic liver failure is a well-established description of a high-mortality syndrome of chronic liver disease (usually cirrhosis) with organ failure. While the exact definition is under refinement, the accepted understanding of this entity is in patients with chronic liver disease and various organs in failure and where systemic inflammation is a major component of the pathobiology. There are limited therapies for a disease with such a poor prognosis, and while improvements in the critical care management and for very few patients, liver transplantation, mean 50% can survive to hospital discharge, rapid application of new therapies is required. Here we explain the current understanding of the immunologic abnormalities seen in acute-on-chronic liver failure across the innate and adaptive immune systems, the role of the hepatic cell death and the gut-liver axis, and recommendations for future research and treatment paradigms.
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Affiliation(s)
- Florent Artru
- Institute of Liver Studies, King's College Hospital, London, United Kingdom; Department of Inflammation Biology, School of Immunology and Microbial Sciences, King's College London, United Kingdom; Liver department and NUMECAN institute, Rennes University Hospital and Rennes University, France
| | - Mark J McPhail
- Institute of Liver Studies, King's College Hospital, London, United Kingdom; Department of Inflammation Biology, School of Immunology and Microbial Sciences, King's College London, United Kingdom.
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50
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Maiwall R, Piano S, Singh V, Caraceni P, Alessandria C, Fernandez J, Soares EC, Kim DJ, Kim SE, Marino M, Vorobioff J, Ribeiro Barea RDC, Merli M, Elkrief L, Vargas V, Krag A, Singh SP, Lesmana LA, Toledo C, Marciano S, Verhelst X, Wong F, Intagliata N, Rabinowich L, Colombato L, Kim SG, Gerbes A, Durand F, Roblero JP, Bhamidimarri KR, Maevskaya M, Fassio E, Kim HS, Hwang JS, Gines P, Bruns T, Gadano A, Angeli P, Sarin SK. Determinants of clinical response to empirical antibiotic treatment in patients with cirrhosis and bacterial and fungal infections-Results from the ICA "Global Study" (EABCIR-Global Study). Hepatology 2024; 79:1019-1032. [PMID: 38047909 DOI: 10.1097/hep.0000000000000653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 06/30/2023] [Indexed: 12/05/2023]
Abstract
BACKGROUND The administration of an appropriate empirical antibiotic treatment is essential in cirrhosis and severe bacterial infections. We aimed to investigate the predictors of clinical response of empirical antibiotic treatment in a prospective cohort of patients with cirrhosis and bacterial and fungal infections included in the International Club of Ascites "Global Study." METHODS Patients hospitalized with cirrhosis and bacterial/fungal infection were prospectively enrolled at 46 centers. Clinical response to antibiotic treatment was defined according to changes in markers of infection/inflammation, vital signs, improvement of organ failure, and results of cultures. RESULTS From October 2015 to September 2016, 1302 patients were included at 46 centers. A clinical response was achieved in only 61% of cases. Independent predictors of lack of clinical response to empirical treatment were C-reactive protein (OR = 1.16; 95% CI = 1.02-1.31), blood leukocyte count (OR = 1.39;95% CI = 1.09-1.77), serum albumin (OR = 0.70; 95% CI = 0.55-0.88), nosocomial infections (OR = 1.96; 95% CI = 1.20-2.38), pneumonia (OR = 1.75; 95% CI = 1.22-2.53), and ineffective treatment according to antibiotic susceptibility test (OR = 5.32; 95% CI = 3.47-8.57). Patients with a lack of clinical response to first-line antibiotic treatment had a significantly lower resolution rate of infections (55% vs. 96%; p < 0.001), a higher incidence of second infections (29% vs. 15%; p < 0.001), shock (35% vs. 7%; p < 0.001) and new organ failures (52% vs. 19 %; p < 0.001) than responders. Clinical response to empirical treatment was an independent predictor of 28-day survival ( subdistribution = 0.20; 95% CI = 0.14-0.27). CONCLUSIONS Four out of 10 patients with cirrhosis do not respond to the first-line antibiotic therapy, leading to lower resolution of infections and higher mortality. Broader-spectrum antibiotics and strategies targeting systemic inflammation may improve prognosis in patients with a high degree of inflammation, low serum albumin levels, and severe liver impairment.
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine, DIMED, University of Padova, Padova, Italy
| | - Virendra Singh
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Carlo Alessandria
- Division of Gastroenterology and Hepatology, Città della Salute e della Scienza Hospital, University of Turin, Turin, Italy
| | - Javier Fernandez
- Liver ICU, Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain
- Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain
- European Foundation of Chronic Liver Failure (EF-Clif), Barcelona, Spain
| | - Elza Cotrim Soares
- Gastroenterology Division, Medicine Department, Faculty of Medical Sciences, University of Campinas (UNICAMP). Campinas, São Paulo, Brazil
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
| | - Sung Eun Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hallym Sacred Heart Hospital, College of Medicine, Hallym University, Anyang city, Republic of Korea
| | - Monica Marino
- Liver Unit, Hospital Dr. Carlos B. Udaondo, Buenos Aires, Argentina
| | | | | | - Manuela Merli
- Gastroenterology and Hepatology Unit, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Laure Elkrief
- Service de Transplantation, Service d'Hépato-gastroentérologie, Hôpitaux Universitaires de Genève, Geneva, Switzerland
| | - Victor Vargas
- Liver Unit, Department of Internal Medicine, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, CIBERehd, Barcelona. Spain
| | - Aleksander Krag
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | | | | | - Claudio Toledo
- Gastroenterology Unit, Hospital Valdivia, Universidad Austral de Chile, Valdivia, Chile
| | - Sebastian Marciano
- Liver Unit and Department of Research, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Xavier Verhelst
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Florence Wong
- Division of Gastroenterology, Department of Medicine, University of Toronto, Ontario, Canada
| | - Nicolas Intagliata
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA
| | - Liane Rabinowich
- Liver Unit, Department of Gastroenterology, Tel-Aviv Medical Center and Tel-Aviv University, Tel-Aviv, Israel
| | - Luis Colombato
- Gastroenterology Department, Buenos Aires British Hospital, Argentine Catholic University (UCA), Buenos Aires, Argentina
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea
| | - Alexander Gerbes
- Department of Medicine II, Liver Centre Munich, University Hospital, LMU Munich, Germany
| | - Francois Durand
- Hepatology & Liver Intensive Care, Hospital Beaujon, Clichy, University Paris Diderot, Paris, France
| | - Juan Pablo Roblero
- Departamento de Medicina, Universidad de Chile Campus Centro, Hospital Clínico San Borja Arriarán, Santiago, Chile
| | | | | | - Eduardo Fassio
- Liver Unit, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina
| | - Hyoung Su Kim
- Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea
| | - Jae Seok Hwang
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Pere Gines
- Liver ICU, Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain
- Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Barcelona, Spain
| | - Tony Bruns
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
- Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany
| | - Adrian Gadano
- Liver Unit and Department of Research, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Paolo Angeli
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine, DIMED, University of Padova, Padova, Italy
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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