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Airola C, Varca S, Del Gaudio A, Pizzolante F. The Covert Side of Ascites in Cirrhosis: Cellular and Molecular Aspects. Biomedicines 2025; 13:680. [PMID: 40149656 PMCID: PMC11940454 DOI: 10.3390/biomedicines13030680] [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: 12/21/2024] [Revised: 02/25/2025] [Accepted: 03/07/2025] [Indexed: 03/29/2025] Open
Abstract
Ascites, a common complication of portal hypertension in cirrhosis, is characterized by the accumulation of fluid within the peritoneal cavity. While traditional theories focus on hemodynamic alterations and renin-angiotensin-aldosterone system (RAAS) activation, recent research highlights the intricate interplay of molecular and cellular mechanisms. Inflammation, mediated by cytokines (interleukin-1, interleukin-4, interleukin-6, tumor necrosis factor-α), chemokines (chemokine ligand 21, C-X-C motif chemokine ligand 12), and reactive oxygen species (ROS), plays a pivotal role. Besides pro-inflammatory cytokines, hepatic stellate cells (HSCs), sinusoidal endothelial cells (SECs), and smooth muscle cells (SMCs) contribute to the process through their activation and altered functions. Once activated, these cell types can worsen ascites accumulationthrough extracellular matrix (ECM) deposition and paracrine signals. Besides this, macrophages, both resident and infiltrating, through their plasticity, participate in this complex crosstalk by promoting inflammation and dysregulating lymphatic system reabsorption. Indeed, the lymphatic system and lymphangiogenesis, essential for fluid reabsorption, is dysregulated in cirrhosis, exacerbating ascites. The gut microbiota and intestinal barrier alterations which occur in cirrhosis and portal hypertension also play a role by inducing inflammation, creating a vicious circle which worsens portal hypertension and fluid accumulation. This review aims to gather these aspects of ascites pathophysiology which are usually less considered and to date have not been addressed using specific therapy. Nonetheless, it emphasizes the need for further research to understand the complex interactions among these mechanisms, ultimately leading to targeted interventions in specific molecular pathways, aiming towards the development of new therapeutic strategies.
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Affiliation(s)
- Carlo Airola
- CEMAD Centro Malattie dell’Apparato Digerente, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (S.V.); (A.D.G.)
- Facoltà di Medicina e Chirurgia, Università Cattolica Sacro Cuore, Largo Agostino Gemelli, 8, 00168 Rome, Italy
| | - Simone Varca
- CEMAD Centro Malattie dell’Apparato Digerente, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (S.V.); (A.D.G.)
- Facoltà di Medicina e Chirurgia, Università Cattolica Sacro Cuore, Largo Agostino Gemelli, 8, 00168 Rome, Italy
| | - Angelo Del Gaudio
- CEMAD Centro Malattie dell’Apparato Digerente, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (S.V.); (A.D.G.)
- Facoltà di Medicina e Chirurgia, Università Cattolica Sacro Cuore, Largo Agostino Gemelli, 8, 00168 Rome, Italy
| | - Fabrizio Pizzolante
- CEMAD Centro Malattie dell’Apparato Digerente, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (S.V.); (A.D.G.)
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Yao F, Luo J, Zhou Q, Wang L, He Z. Development and validation of a machine learning-based prediction model for hepatorenal syndrome in liver cirrhosis patients using MIMIC-IV and eICU databases. Sci Rep 2025; 15:2743. [PMID: 39837961 PMCID: PMC11751441 DOI: 10.1038/s41598-025-86674-9] [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: 11/18/2024] [Accepted: 01/13/2025] [Indexed: 01/23/2025] Open
Abstract
Hepatorenal syndrome (HRS) is a key contributor to poor prognosis in liver cirrhosis. This study aims to leverage the database to build a predictive model for early identification of high-risk patients. From two sizable public databases, we retrieved pertinent information about the cirrhosis patients' therapies, comorbidities, laboratory results, and demographics. Patients from the eICU database served as a test set for external validation, while patients from the MIMIC database were divided into training and validation groups. Variables were screened using LASSO regression, Extreme Gradient Boosting (XG Boost), and Random Forest (RF). Core risk factors were determined from the intersection of the three methods. A predictive model was constructed using multivariable logistic regression and visualized via a nomogram. Model performance was assessed using ROC curves, decision curve analysis (DCA), clinical impact curves (CIC), and calibration curves. Eight critical variables associated with HRS were identified using machine learning methods. The final predictive model, based on five key variables-spontaneous bacterial peritonitis, red blood cell count, creatinine, activated partial thromboplastin time, and total bilirubin-showed excellent discrimination, with AUCs of 0.832 (95% CI 0.8069-0.8563) in the training set and 0.8415 (95% CI 0.8042-0.8789) in the validation set. The AUC in the external test set was 0.8212 (95% CI 0.7784-0.864). By integrating the MIMIC-IV database and machine learning algorithms, we developed an effective predictive model for HRS in liver cirrhosis patients, providing a robust tool for early clinical intervention.
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Affiliation(s)
- Fengwei Yao
- Department of Gastrointestinal Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People's Republic of China
| | - Ji Luo
- Department of Gastrointestinal Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People's Republic of China
| | - Qian Zhou
- Department of Gastrointestinal Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People's Republic of China
| | - Luhua Wang
- Department of Gastrointestinal Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People's Republic of China
| | - Zhijun He
- Department of Gastrointestinal Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People's Republic of China.
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Khemichian S, Nadim MK, Terrault NA. Update on Hepatorenal Syndrome: From Pathophysiology to Treatment. Annu Rev Med 2025; 76:373-387. [PMID: 39869432 DOI: 10.1146/annurev-med-050223-112947] [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: 01/29/2025]
Abstract
Hepatorenal syndrome-acute kidney injury (HRS-AKI) occurs in the setting of advanced chronic liver disease, portal hypertension, and ascites. HRS-AKI is found in ∼20% of patients presenting to the hospital with AKI, but it may coexist with other causes of AKI and/or with preexisting chronic kidney disease, thereby making the diagnosis challenging. Novel biomarkers such as urinary neutrophil gelatinase-associated lipocalin may be useful. While HRS-AKI is a functional form of AKI related to circulatory and neurohormonal dysfunction, there is increasing recognition of the importance of systemic inflammation and the renal microenvironment. Early diagnosis and initiation of HRS-AKI-specific treatment can improve outcomes. The mainstay of therapy is a vasoconstrictor (terlipressin or norepinephrine) combined with albumin, which achieves resolution of HRS in 40-50% of cases. Liver transplantation is the only option for patients failing to respond to medical therapies.
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Affiliation(s)
- Saro Khemichian
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA;
| | - Mitra K Nadim
- Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Norah A Terrault
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA;
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Cullaro G, Allegretti AS, Fenton C, Ge J, Patidar KR, Rubin J, Sharma A, Lai JC. The association between mean arterial pressure and acute kidney injury reversal among patients with decompensated cirrhosis. Hepatology 2025; 81:126-135. [PMID: 38537129 PMCID: PMC11427603 DOI: 10.1097/hep.0000000000000858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 03/06/2024] [Indexed: 04/05/2024]
Abstract
BACKGROUND AND AIMS This study informs how mean arterial pressure (MAP) impacts acute kidney injury (AKI) recovery among all patients hospitalized with cirrhosis, regardless of etiology. APPROACH AND RESULTS We identified incident AKI episodes among subjects in our cohort of patients with decompensated cirrhosis. AKI was defined as a ≥50% increase in creatinine from an outpatient baseline (≥7 days prior) that required hospitalization. Linear mixed effects models were completed to determine the impact between AKI recovery, MAP, and time. To determine the impact of MAP on AKI reversal, we completed time-dependent Cox regression models with time beginning at the time of peak creatinine and ending at death, discharge, or AKI reversal, among those hospitalized with AKI and those with persistent AKI (≥48 h) We identified 702 hospitalized patients with cirrhosis with AKI. We found those with AKI reversal had, on average, higher MAP (2.1 mm Hg, p <0.05) and a greater increase in MAP over time (0.1 mm Hg per hour, p <0.001). Among all 702 hospitalized patients with AKI and adjusted for confounders, each 5 mm Hg increase in MAP was associated with 1.07× the hazard of AKI reversal ( p <0.01). Similarly, among those with persistent AKI after adjusting for confounders, each 5 mm Hg increase in MAP was associated with a 1.19× greater likelihood of AKI reversal ( p <0.001). DISCUSSION Our data demonstrate that MAP significantly increases the likelihood of AKI recovery regardless of severity or injury or AKI phenotype. We believe these data highlight the importance of MAP as a clinical tool to promote kidney function recovery among patients with cirrhosis hospitalized with AKI.
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Affiliation(s)
- Giuseppe Cullaro
- Department of Medicine, University of California-San Francisco, San Francisco, California, USA
| | - Andrew S. Allegretti
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Cynthia Fenton
- Department of Medicine, University of California-San Francisco, San Francisco, California, USA
| | - Jin Ge
- Department of Medicine, University of California-San Francisco, San Francisco, California, USA
| | - Kavish R. Patidar
- Section of Gastroenterology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston Texas, USA
| | - Jessica Rubin
- Department of Medicine, University of California-San Francisco, San Francisco, California, USA
| | - Arjun Sharma
- Department of Medicine, University of California-San Francisco, San Francisco, California, USA
| | - Jennifer C. Lai
- Department of Medicine, University of California-San Francisco, San Francisco, California, USA
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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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Xu X, Gao F, Wang T, Yang Z, Zhao Q, Qi X. Association of non-selective β blockers with the development of renal dysfunction in liver cirrhosis: a systematic review and meta-analysis. Ann Med 2024; 56:2305935. [PMID: 38271554 PMCID: PMC10812853 DOI: 10.1080/07853890.2024.2305935] [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: 04/03/2023] [Accepted: 01/09/2024] [Indexed: 01/27/2024] Open
Abstract
BACKGROUND & AIMS Non-selective β blockers (NSBBs) may negatively influence renal function through decreasing heart rate and cardiac output. This study aimed to systematically investigate their association. METHODS PubMed, EMBASE, and Cochrane library databases were searched to identify all relevant studies evaluating the association of NSBBs with renal dysfunction in cirrhotic patients. Unadjusted and adjusted data were separately extracted. Odds ratios (ORs) and hazard ratios (HRs) were pooled. Subgroup meta-analyses were performed according to the proportions of ascites and Child-Pugh class B/C and the mean model for end-stage liver disease (MELD) score. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework. RESULTS Fourteen studies were finally included. Based on unadjusted data, NSBBs significantly increased the risk of developing renal dysfunction (OR = 1.49; p = 0.03), and this association remained significant in subgroup analyses of studies where the proportions of ascites was >70% and Child-Pugh class B/C was 100%. Based on adjusted data with propensity score matching (adjusted OR = 0.61; p = 0.08) and multivariable regression modelling (adjusted HR = 0.86; p = 0.713), NSBBs did not increase the risk of developing renal dysfunction, and this association remained not significant in subgroup analyses of studies where the proportions of ascites was >70% and <70%, the proportion of Child-Pugh class B/C was <100%, and the mean MELD score was <15. The quality of evidence was very low for all meta-analyses. CONCLUSIONS NSBBs may not be associated with the development of renal dysfunction in liver cirrhosis. However, more evidence is required to clarify their association in specific populations.
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Affiliation(s)
- Xiangbo Xu
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, China
| | - Fangbo Gao
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
| | - Ting Wang
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
| | - Zuyao Yang
- Division of Epidemiology, The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China
| | - Qingchun Zhao
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
- Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, China
| | - Xingshun Qi
- Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
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Terbah R, Koshy AN, Majumdar A, Vaz K, Testro A, Sinclair M. Long-Term Continuous Terlipressin Infusion Improves Cardiac Reserve in Patients With Decompensated Cirrhosis. Clin Gastroenterol Hepatol 2024:S1542-3565(24)00778-X. [PMID: 39209185 DOI: 10.1016/j.cgh.2024.08.010] [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: 06/24/2024] [Revised: 08/06/2024] [Accepted: 08/13/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND AND AIMS Cardiac dysfunction is a key factor in the pathogenesis of hepatorenal syndrome, for which terlipressin is the recommended first-line treatment. This study investigates whether long-term terlipressin can ameliorate the subclinical cardiac dysfunction observed in decompensated cirrhosis. METHODS Twenty-two patients with decompensated cirrhosis and ascites enrolled in a prospective study of home continuous terlipressin infusion were included. Cardiac function was assessed using dobutamine stress echocardiogram before and after 12 weeks of terlipressin. The primary outcome was the impact of terlipressin on cardiac reserve, the change in cardiac output (CO) in response to stress. RESULTS The median age was 61 years (interquartile range, 56-64 years), the median Model for End-Stage Liver Disease score was 15 (interquartile range, 12.3-17.0), and 72.7% were male. The increase in CO in response to low-dose dobutamine was significantly higher following terlipressin (↑4.0 L/min [↑57.8%]) as compared with baseline (↑1.8 L/min [21.3%]) (P = .0001). The proportion of patients with impaired cardiac reserve (defined by ΔCO <25% after low-dose dobutamine) reduced from 81.8% at baseline to 40.9% after terlipressin, (P = .02), driven primarily by improvement in inotropic function. Resting CO decreased significantly after terlipressin from 8.9 ± 2.2 L/min to 7.2 ± 1.8 L/min (normal range 5-6 L/min) (P < .001), due to a decrease in stroke volume from 108 to 86 mL/beat (P = .006). CONCLUSIONS Long-term continuous terlipressin infusion resulted in a significant increase in cardiac reserve and attenuation of the hyperdynamic state usually observed in decompensated cirrhosis. These data provide important mechanistic insight into the pathogenesis and reversibility of cardiac dysfunction in cirrhosis. Future studies are required to evaluate whether long-term terlipressin can prevent hepatic decompensating events such as hepatorenal syndrome in high-risk individuals. Australian New Zealand Clinical Trials Registry, Number: ACTRN12619000891123.
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Affiliation(s)
- Ryma Terbah
- Department of Medicine, University of Melbourne, Victoria, Australia; Victorian Liver Transplant Unit, Austin Health, Heidelberg, Australia; Australian Centre for Transplantation Excellence and Research, Melbourne, Australia; Australian Cardiovascular Collaborative in Liver Transplant Medicine, Melbourne, Australia
| | - Anoop N Koshy
- Department of Medicine, University of Melbourne, Victoria, Australia; Victorian Liver Transplant Unit, Austin Health, Heidelberg, Australia; Australian Centre for Transplantation Excellence and Research, Melbourne, Australia; Australian Cardiovascular Collaborative in Liver Transplant Medicine, Melbourne, Australia; Department of Cardiology, Austin Health, Heidelberg, Australia
| | - Avik Majumdar
- Department of Medicine, University of Melbourne, Victoria, Australia; Victorian Liver Transplant Unit, Austin Health, Heidelberg, Australia; Australian Centre for Transplantation Excellence and Research, Melbourne, Australia; Australian Cardiovascular Collaborative in Liver Transplant Medicine, Melbourne, Australia
| | - Karl Vaz
- Department of Medicine, University of Melbourne, Victoria, Australia; Victorian Liver Transplant Unit, Austin Health, Heidelberg, Australia; Australian Centre for Transplantation Excellence and Research, Melbourne, Australia; Australian Cardiovascular Collaborative in Liver Transplant Medicine, Melbourne, Australia
| | - Adam Testro
- Department of Medicine, University of Melbourne, Victoria, Australia; Victorian Liver Transplant Unit, Austin Health, Heidelberg, Australia; Australian Centre for Transplantation Excellence and Research, Melbourne, Australia; Australian Cardiovascular Collaborative in Liver Transplant Medicine, Melbourne, Australia
| | - Marie Sinclair
- Department of Medicine, University of Melbourne, Victoria, Australia; Victorian Liver Transplant Unit, Austin Health, Heidelberg, Australia; Australian Centre for Transplantation Excellence and Research, Melbourne, Australia; Australian Cardiovascular Collaborative in Liver Transplant Medicine, Melbourne, Australia.
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8
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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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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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Pose E, Piano S, Juanola A, Ginès P. Hepatorenal Syndrome in Cirrhosis. Gastroenterology 2024; 166:588-604.e1. [PMID: 38246506 DOI: 10.1053/j.gastro.2023.11.306] [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: 06/16/2023] [Revised: 11/10/2023] [Accepted: 11/19/2023] [Indexed: 01/23/2024]
Abstract
Hepatorenal syndrome (HRS) is a form of kidney dysfunction that characteristically occurs in liver cirrhosis. It is characterized by a marked impairment of kidney function in response to circulatory and hemodynamic alterations that occur in advanced stages of liver cirrhosis, aggravated by systemic inflammation and bacterial translocation. The classical definitions of the types of HRS have been recently revisited and 2 forms of HRS have been redefined: the acute form, referred to as acute kidney injury (HRS-AKI), and the chronic form, referred to as chronic kidney disease. HRS-AKI is one of the most severe forms of AKI in patients with cirrhosis and it consists of an abrupt impairment of kidney function, frequently triggered by an infection, appearing in the setting of advanced decompensated cirrhosis. Differential diagnosis with other causes of AKI is crucial because HRS-AKI requires a specific treatment. Differential diagnosis with AKI-acute tubular necrosis may be challenging and kidney biomarkers may be useful in this setting. Treatment of HRS-AKI is based on the administration of vasoconstrictor drugs in combination with volume expansion with albumin. Prognosis of HRS-AKI is poor, and the ideal definitive treatment consists of liver transplantation or simultaneous liver-kidney transplantation. HRS-AKI has a big impact on patients' quality of life. Management of HRS-AKI remains challenging in specific situations such as alcohol-associated hepatitis or metabolic-associated steatotic liver disease cirrhosis. Developing preventive measures for HRS-AKI, improving its early identification, discovering new biomarkers for differential diagnosis, and improving the response to therapy are some of the unmet needs in the field of HRS-AKI.
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Affiliation(s)
- Elisa Pose
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Salvatore Piano
- Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine - DIMED, University of Padova, Padova, Italy
| | - Adrià Juanola
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Pere Ginès
- Liver Unit, Hospital Clínic of Barcelona, Barcelona, Catalunya, Spain; School of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalunya, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain; Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.
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11
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Almeida F, Sousa A. Cirrhotic cardiomyopathy: Pathogenesis, clinical features, diagnosis, treatment and prognosis. Rev Port Cardiol 2024; 43:203-212. [PMID: 38142819 DOI: 10.1016/j.repc.2023.07.010] [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: 04/06/2023] [Revised: 06/09/2023] [Accepted: 07/30/2023] [Indexed: 12/26/2023] Open
Abstract
Cardiac dysfunction among cirrhotic patients has long been recognized in the medical community. While it was originally believed to be a direct result of alcohol toxicity, in the last 30 years cirrhotic cardiomyopathy (CCM) has been described as a syndrome characterized by chronic cardiac dysfunction in cirrhotic patients in the absence of known cardiac disease, regardless of the etiology of cirrhosis. CCM occurs in about 60% of patients with cirrhosis and plays a critical role in disease progression and treatment outcomes. Due to its predominantly asymptomatic course, diagnosing CCM is challenging and requires a high index of suspicion and a multiparametric approach. Patients with CCM usually present with the following triad: impaired myocardial contractile response to exercise, inadequate ventricular relaxation, and electrophysiological abnormalities (notably prolonged QT interval). In recent years, research in this area has grown expeditiously and a new set of diagnostic criteria has been developed by the Cirrhotic Cardiomyopathy Consortium, to properly identify patients with CCM. Nevertheless, CCM is still largely unknown among clinicians, and a major part of its pathophysiology and treatment is yet to be understood. In the present work, we aim to compile and summarize the available data on the pathogenesis, clinical features, diagnosis, treatment, and prognosis of CCM.
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Affiliation(s)
| | - Alexandra Sousa
- Cardiology Department, Unidade Local de Saúde de Entre o Douro e Vouga, Santa Maria da Feira, Portugal; Department of Medicine, Faculty of Medicine, University of Porto, Porto, Portugal; CINTESIS - Centre for Health Technology and Services Research, Porto, Portugal; RISE - Health Research Network, Porto, Portugal
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12
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Velez JCQ, Latt N, Rodby RA. Pathophysiology of Hepatorenal Syndrome. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:87-99. [PMID: 38649221 DOI: 10.1053/j.akdh.2024.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 12/17/2023] [Accepted: 01/02/2024] [Indexed: 04/25/2024]
Abstract
Hepatorenal syndrome type 1 (HRS-1) is a unique form of acute kidney injury that affects individuals with decompensated cirrhosis with ascites. The primary mechanism leading to reduction of kidney function in HRS-1 is hemodynamic in nature. Cumulative evidence points to a cascade of events that led to a profound reduction in kidney perfusion. A state of increased intrahepatic vascular resistance characteristic of advanced cirrhosis and portal hypertension is accompanied by maladaptive peripheral arterial vasodilation and reduction in systemic vascular resistance and mean arterial pressure. As a result of a fall in effective arterial blood volume, there is a compensatory activation of the sympathetic nervous system and the renin-angiotensin system, local renal vasoconstriction, loss of renal autoregulation, decrease in renal blood flow, and ultimately a fall in glomerular filtration rate. Systemic release of nitric oxide stimulated by the fibrotic liver, bacterial translocation, and inflammation constitute key components of the pathogenesis. While angiotensin II and noradrenaline remain the critical mediators of renal arterial and arteriolar vasoconstriction, other novel molecules have been recently implicated. Although the above-described mechanistic pathway remains the backbone of the pathogenesis of HRS-1, other noxious elements may be present in advanced cirrhosis and likely contribute to the renal impairment. Direct liver-kidney crosstalk via the hepatorenal sympathetic reflex can further reduce renal blood flow independently of the systemic derangements. Tense ascites may lead to intraabdominal hypertension and abdominal compartment syndrome. Cardio-hemodynamic processes have also been increasingly recognized. Porto-pulmonary hypertension, cirrhotic cardiomyopathy, and abdominal compartment syndrome may lead to renal congestion and complicate the course of HRS-1. In addition, a degree of ischemic or toxic (cholemic) tubular injury may overlap with the underlying circulatory dysfunction and further exacerbate the course of acute kidney injury. Improving our understanding of the pathogenesis of HRS-1 may lead to improvements in therapeutic options for this seriously ill population.
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Affiliation(s)
- Juan Carlos Q Velez
- Department of Nephrology, Ochsner Health, New Orleans, LA; Ochsner Clinical School, The University of Queensland, Brisbane, QLD, Australia.
| | - Nyan Latt
- Virtua Center for Liver Disease, Virtua Health, Toms River, NJ
| | - Roger A Rodby
- Division of Nephrology, Rush University School of Medicine, Chicago, IL
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13
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Wu HHL, Rakisheva A, Ponnusamy A, Chinnadurai R. Hepatocardiorenal syndrome in liver cirrhosis: Recognition of a new entity? World J Gastroenterol 2024; 30:128-136. [PMID: 38312119 PMCID: PMC10835518 DOI: 10.3748/wjg.v30.i2.128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 12/05/2023] [Accepted: 12/28/2023] [Indexed: 01/12/2024] Open
Abstract
Emerging evidence and perspectives have pointed towards the heart playing an important role in hepatorenal syndrome (HRS), outside of conventional understanding that liver cirrhosis is traditionally considered the sole origin of a cascade of pathophysiological mechanisms directly affecting the kidneys in this context. In the absence of established heart disease, cirrhotic cardiomyopathy may occur more frequently in those with liver cirrhosis and kidney disease. It is a specific form of cardiac dysfunction characterized by blunted contractile responsiveness to stress stimuli and altered diastolic relaxation with electrophysiological abnormalities. Despite the clinical description of these potential cardiac-related complications of the liver, the role of the heart has traditionally been an overlooked aspect of circulatory dysfunction in HRS. Yet from a physiological sense, temporality (prior onset) of cardiorenal interactions in HRS and positive effects stemming from portosystemic shunting demonstrated an important role of the heart in the development and progression of kidney dysfunction in cirrhotic patients. In this review, we discuss current concepts surrounding how the heart may influence the development and progression of HRS, and the role of systemic inflammation and endothelial dysfunction causing circulatory dysfunction within this setting. The temporality of heart and kidney dysfunction in HRS will be discussed. For a subgroup of patients who receive portosystemic shunting, the dynamics of cardiorenal interactions following treatment is reviewed. Continued research to determine the unknowns in this topic is anticipated, hopefully to further clarify the intricacies surrounding the liver-heart-kidney connection and improve strategies for management.
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Affiliation(s)
- Henry H L Wu
- Renal Research, Kolling Institute of Medical Research, Royal North Shore Hospital & The University of Sydney, St. Leonards (Sydney) 2065, New South Wales, Australia
| | - Amina Rakisheva
- Department of Cardiology, City Cardiological Center, Almaty 050000, Kazakhstan
| | - Arvind Ponnusamy
- Department of Renal Medicine, Royal Preston Hospital, Preston PR2 9HT, United Kingdom
| | - Rajkumar Chinnadurai
- Donal O’Donoghue Renal Research Centre & Department of Renal Medicine, Northern Care Alliance National Health Service Foundation Trust, Salford M6 8HD, United Kingdom
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14
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Lan NTN, Lieu DQ, Anh TN, Thuong LH, Tuong TTK, Bang MH. Characteristics and Related Factors of Bacterial Infection Among Patients With Cirrhosis. Mater Sociomed 2024; 36:90-96. [PMID: 38590588 PMCID: PMC10999149 DOI: 10.5455/msm.2024.36.90-96] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 02/25/2024] [Indexed: 04/10/2024] Open
Abstract
Background Infection causes cirrhosis to decompensate, affecting liver function and resulting in several complications, including esophageal variceal hemorrhage, hepatic encephalopathy, and hepatorenal syndrome. Objective: This study aimed to identify the prevalence, essential features, and related factors of bacterial infection among patients with cirrhosis in Vietnam. Methods This retrospective study included 317 patients diagnosed with cirrhosis, who were divided into two groups: group 1 including 125 patients with bacterial infection and group 2 including 192 patients without bacterial infection. Infection was diagnosed on the basis of its localization. Results Spontaneous bacterial peritonitis (SBP; 31.2%) and pneumonia (28.8%) were the most common infections identified. The procalcitonin (PCT) level had a strong diagnostic value with an area under the curve value of 0.868. The most common type of gram-negative bacteria was Escherichia coli, while the gram-positive bacteria seen were Staphylococcus, Enterococcus, and Streptococcus among the patients with infection. In the logistic regression analysis, Child-Pugh class B and C (p<0.001, OR=4.14, CI=1.90-9.03; OR=4.76, CI=2.03-11.16, respectively) and the presence of acute kidney injury (p=0.009, OR=2.57, CI=1.27-5.22) and gastrointestinal hemorrhage (p=0.035, OR=0.39, CI=0.16-0.94) significantly differed between the groups. Conclusion The most prevalent type of bacterial infection in patients with cirrhosis is SBP, with gram-negative bacteria being the most common cause. The PCT level is useful in identifying infection in patients with cirrhosis. Decompensated cirrhosis is linked to a higher risk of infection.
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Affiliation(s)
| | - Dau Quang Lieu
- Department of Internal Medicine, Hanoi Medical University Hospital, Hanoi, Vietnam
| | - Tran Ngoc Anh
- Department of Internal Medicine, Hanoi Medical University Hospital, Hanoi, Vietnam
- Department of Internal Medicine, Hanoi Medical University, Hanoi, Vietnam
| | - Le Hoai Thuong
- Department of Internal Medicine, Hanoi Medical University, Hanoi, Vietnam
| | - Tran-Thi Khanh Tuong
- Department of Internal Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam
| | - Mai Hong Bang
- Department of Gastroenterology, 108 Military Central Hospital, Hanoi, Vietnam
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15
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Badura K, Frąk W, Hajdys J, Majchrowicz G, Młynarska E, Rysz J, Franczyk B. Hepatorenal Syndrome-Novel Insights into Diagnostics and Treatment. Int J Mol Sci 2023; 24:17469. [PMID: 38139297 PMCID: PMC10744165 DOI: 10.3390/ijms242417469] [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: 10/30/2023] [Revised: 12/09/2023] [Accepted: 12/11/2023] [Indexed: 12/24/2023] Open
Abstract
Hepatorenal syndrome (HRS) is a disorder associated with cirrhosis and renal impairment, with portal hypertension as its major underlying cause. Moreover, HRS is the third most common cause of acute kidney injury, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of HRS. We discuss pathogenesis associated with HRS. Mechanisms such as dysfunction of the circulatory system, bacterial infection, inflammation, impaired renal autoregulation, circulatory, and others, which have been identified as critical pathways for development of HRS, have become easier to diagnose in recent years. Additionally, relatively recently, renal dysfunction biomarkers have been found indicating renal injury, which are involved in the pathophysiology of HRS. This review also summarizes the available information on the management of HRS, focusing on vasoconstrictive drugs, renal replacement therapy, and liver transplant together with currently being investigated novel therapies. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of HRS.
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Affiliation(s)
- Krzysztof Badura
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Weronika Frąk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Joanna Hajdys
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Gabriela Majchrowicz
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Ewelina Młynarska
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrocardiology, Medical University of Lodz, Ul. Zeromskiego 113, 90-549 Lodz, Poland
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16
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Juanola A, Ma AT, de Wit K, Gananandan K, Roux O, Zaccherini G, Jiménez C, Tonon M, Solé C, Villaseca C, Uschner FE, Graupera I, Pose E, Moreta MJ, Campion D, Beuers U, Mookerjee RP, Francoz C, Durand F, Vargas V, Piano S, Alonso S, Trebicka J, Laleman W, Asrani SK, Soriano G, Alessandria C, Serra-Burriel M, Morales-Ruiz M, Torres F, Allegretti AS, Krag A, Caraceni P, Watson H, Abraldes JG, Solà E, Kamath PS, Hernaez R, Ginès P. Novel prognostic biomarkers in decompensated cirrhosis: a systematic review and meta-analysis. Gut 2023; 73:156-165. [PMID: 37884354 DOI: 10.1136/gutjnl-2023-329923] [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: 03/22/2023] [Accepted: 09/18/2023] [Indexed: 10/28/2023]
Abstract
BACKGROUND Patients with decompensated cirrhosis experience high mortality rates. Current prognostic scores, including the model for end-stage liver disease (MELD), may underperform in settings other than in those they were initially developed. Novel biomarkers have been proposed to improve prognostication accuracy and even to predict development of complications. METHODS We performed a systematic review and meta-analysis on novel urine and blood biomarkers and their ability to predict 90-day mortality in patients with decompensated cirrhosis. Secondary outcomes included 28-day and 1-year mortality, and development of acute-on-chronic liver failure, acute kidney injury and other complications. To overcome differences in units, temporal changes in assays and reporting heterogeneity, we used the ratio of means (RoM) as measure of association for assessing strength in predicting outcomes. An RoM>1 implies that the mean biomarker level is higher in those that develop the outcome than in those that do not. RESULTS Of 6629 unique references, 103 were included, reporting on 29 different biomarkers, with a total of 31 362 biomarker patients. Most studies were prospective cohorts of hospitalised patients (median Child-Pugh-Turcotte score of 9 and MELD score of 18). The pooled 90-day mortality rate was 0.27 (95% CI 0.24 to 0.29). The RoM for predicting 90-day mortality was highest for interleukin 6 (IL-6) (2.56, 95% CI 2.39 to 2.74), followed by urinary neutrophil gelatinase-associated lipocalin (uNGAL) (2.42, 95% CI 2.20 to 2.66) and copeptin (2.33, 95% CI 2.17 to 2.50). These RoMs were all higher than for MELD (1.44, 95% CI 1.42 to 1.46). CONCLUSION Novel biomarkers, including IL-6, uNGAL and copeptin, can probably improve prognostication of patients with decompensated cirrhosis compared with MELD alone.
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Affiliation(s)
- Adrià Juanola
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
- Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas, Barcelona, Spain
| | - Ann Thu Ma
- Toronto Centre for Liver Disease Francis Family Liver Clinic, Toronto General Hospital, Toronto, Ontario, Canada
| | - Koos de Wit
- Gastroenterology and Hepatology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands
| | - Kohilan Gananandan
- Institute for Liver and Digestive Health, University College London, London, UK
| | - Olivier Roux
- Department of Hepatology, Beaujon Hospital, Clichy, France
| | - Giacomo Zaccherini
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-related Diseases, University of Bologna Hospital of Bologna Sant'Orsola-Malpighi Polyclinic, Bologna, Italy
| | - César Jiménez
- Liver Unit, Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain
| | - Marta Tonon
- Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Cristina Solé
- Department of Gastroenterology and Hepatology, Consorci Corporació Sanitària Parc Taulí, Sabadell, Spain
| | - Clara Villaseca
- Digestive Disease Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Frank E Uschner
- Department of Internal Medicine B, University of Münster, Munster, Germany
| | - Isabel Graupera
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
- Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas, Barcelona, Spain
| | - Elisa Pose
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
- Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas, Barcelona, Spain
| | - Maria José Moreta
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
| | - Daniela Campion
- Division of Gastroenterology and Hepatology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Torino, Italy
| | - Ulrich Beuers
- Gastroenterology & Hepatology, Amsterdam University Medical Centres, Amsterdam, The Netherlands
| | - Rajeshawar P Mookerjee
- Institute of Liver and Digestive Health, University College London Medical School, London, UK
| | - Claire Francoz
- Department of Hepatology, Beaujon Hospital, Clichy, France
| | - Francois Durand
- DHU Unity, Pôle des Maladies de l'Appareil Digestif, Service d'Hépatologie, Centre de Référence des Maladies Vasculaires du Foie, Hôpital Beaujon, AP-HP, Clichy, France
- Université Denis Diderot-Paris 7, Paris, France
| | - Victor Vargas
- Liver Unit, Department of Internal Medicine, Hospital Vall d'Hebron, Barcelona, Spain
| | - Salvatore Piano
- Department of Medicine (DIMED), University of Padova, Padova, Italy
| | - Sonia Alonso
- Digestive Disease Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Jonel Trebicka
- Department of Internal Medicine B, University of Münster, Munster, Germany
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Wim Laleman
- Division of Liver and Biliopanreatic Disorders, KU Leuven, University of Leuven, Leuven, Belgium
| | - Sumeet K Asrani
- Division of Hepatology, Department of Medicine, Baylor University Medical Center at Dallas, Dallas, Texas, USA
| | - German Soriano
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Carlo Alessandria
- Division of Gastroenterology and Hepatology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Torino, Italy
| | - Miquel Serra-Burriel
- University of Zurich Institute of Epidemiology Biostatistics and Prevention, Zurich, Switzerland
| | - Manuel Morales-Ruiz
- Biochemistry and Molecular Genetics Department-CDB, Hospital Clinic de Barcelona, Barcelona, Spain
| | - Ferran Torres
- Biostatistics and Data Management Core Facility, IDIBAPS, Hospital Clinic Barcelona, Barcelona, Spain
- Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Andrew S Allegretti
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Aleksander Krag
- Department of Gastroenterology, Odense University Hospital, University of Southern Denmark, Odense, Denmark
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | | | - Juan G Abraldes
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
| | - Elsa Solà
- Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, California, USA
| | - Patrick S Kamath
- Gastroenterology and Hepatology, Mayo Medical School, Rochester, Minnesota, USA
| | - Ruben Hernaez
- Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
- Gastroenterology and Hepatology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Pere Ginès
- Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain
- Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas, Barcelona, Spain
- Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain
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17
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Jung CY, Chang JW. Hepatorenal syndrome: Current concepts and future perspectives. Clin Mol Hepatol 2023; 29:891-908. [PMID: 37050843 PMCID: PMC10577351 DOI: 10.3350/cmh.2023.0024] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 04/10/2023] [Accepted: 04/10/2023] [Indexed: 04/14/2023] Open
Abstract
Hepatorenal syndrome (HRS), a progressive but potentially reversible deterioration of kidney function, remains a major complication in patients with advanced cirrhosis, often leading to death before liver transplantation (LT). Recent updates in the pathophysiology, definition, and classification of HRS have led to a complete revision of the nomenclature and diagnostic criteria for HRS type 1, which was renamed HRS-acute kidney injury (AKI). HRS is characterized by severe impairment of kidney function due to increased splanchnic blood flow, activation of several vasoconstriction factors, severe vasoconstriction of the renal arteries in the absence of kidney histologic abnormalities, nitric oxide dysfunction, and systemic inflammation. Diagnosis of HRS remains a challenge because of the lack of specific diagnostic biomarkers that accurately distinguishes structural from functional AKI, and mainly involves the differential diagnosis from other forms of AKI, particularly acute tubular necrosis. The optimal treatment of HRS is LT. While awaiting LT, treatment options include vasoconstrictor drugs to counteract splanchnic arterial vasodilation and plasma volume expansion by intravenous albumin infusion. In patients with HRS unresponsive to pharmacological treatment and with conventional indications for kidney replacement therapy (KRT), such as volume overload, uremia, or electrolyte imbalances, KRT may be applied as a bridging therapy to transplantation. Other interventions, such as transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Although recently developed novel therapies have potential to improve outcomes of patients with HRS, further studies are warranted to validate the efficacy of these novel agents.
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Affiliation(s)
- Chan-Young Jung
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jai Won Chang
- Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Dawit L, Lee V, Lehoang D, Furey C, Chowdhury A, Mai TA, Angajala V, Park JH, Khadarian K, She R, Vergara-Lluri M, Kahn J, Dodge JL, Saito T. Clinical Significance of Ascitic Fluid Polymorphonuclear Leukocyte Percentage in Patients With Cirrhosis Without Spontaneous Bacterial Peritonitis. Clin Transl Gastroenterol 2023; 14:e00614. [PMID: 37436155 PMCID: PMC10522094 DOI: 10.14309/ctg.0000000000000614] [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: 02/05/2023] [Revised: 06/10/2023] [Accepted: 06/26/2023] [Indexed: 07/13/2023] Open
Abstract
INTRODUCTION Absolute polymorphonuclear leukocyte (PMN) count (PMN-C) ≥250 cells/mm 3 in ascites is the diagnostic hallmark of spontaneous bacterial peritonitis (SBP) and is associated with high morbidity and mortality. However, the clinical significance of ascitic PMN percentage (PMN-%) and PMN-C in the absence of SBP as additional biomarkers for mortality and future incidence of SBP has not been determined. METHODS This retrospective cohort included adults with cirrhosis undergoing first-recorded paracentesis with initial PMN-C < 250 cells/mm 3 at 2 tertiary medical centers between 2015 and 2020. Patients with prior SBP were excluded. Outcomes were death and SBP development. Cox regression estimated hazard ratios (HRs) for risk of death and SBP development and Akaike information criterion to compare model fit. RESULTS Three hundred eighty-four adults (73% male, median age 58 years, 67% with alcohol-associated cirrhosis, median PMN-C 14 cells/mm 3 [interquartile range 5-34], and median PMN-% 10% [interquartile range 4-20]) were included in this study. Univariate risk of death increased 10% per 25-unit increase in PMN-C (95% confidence interval 1.01-1.21, P = 0.03) and 19% per 10-unit increase in PMN-% (95% confidence interval 1.06-1.33, P = 0.003) with PMN-% demonstrating better model fit in assessing mortality risk (Akaike information criterion: 1,044 vs 1,048, respectively). In models adjusted for age, chronic hepatitis C virus infection, and Model for End-Stage Liver Disease-Sodium, PMN-% was associated with risk of death (PMN-% 10%-29%, HR 1.17, P = 0.50; PMN-% ≥ 30% group, HR 1.94, P = 0.03; vs PMN-% < 10%) and SBP development (PMN-% 10%-29%, HR 1.68, P = 0.07; PMN-% ≥ 30%, HR 3.48, P < 0.001; vs PMN-% < 10%). DISCUSSION Our results suggest PMN-% at first paracentesis represents a better biomarker compared with PMN-C for assessing risk of death and future SBP development in patients with PMN-C < 250 cells/mm 3 .
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Affiliation(s)
- Lillian Dawit
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Vivian Lee
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - David Lehoang
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Cameron Furey
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Aneesa Chowdhury
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Thu Anne Mai
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Varun Angajala
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Joo Hye Park
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Kevork Khadarian
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Rosemary She
- Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Maria Vergara-Lluri
- Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Jeffrey Kahn
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Jennifer L. Dodge
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
- USC Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Takeshi Saito
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
- Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
- USC Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
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Roy P, Minhaz N, Shah-Riar P, Simona SY, Tasha T, Binte Hasan T, Abbasi FK, Alam F, Nila SA, Akter J, Akter S, Biswas S, Sultana N. A Comprehensive Systematic Review of the Latest Management Strategies for Hepatorenal Syndrome: A Complicated Syndrome to Tackle. Cureus 2023; 15:e43073. [PMID: 37680416 PMCID: PMC10481992 DOI: 10.7759/cureus.43073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/06/2023] [Indexed: 09/09/2023] Open
Abstract
Hepatorenal syndrome (HRS), defined by the extreme manifestation of renal impairment in patients with cirrhosis, is characterized by reduced renal blood flow and glomerular filtration rate. It is diagnosed with reduced kidney function confirming the absence of intrinsic kidney disease, such as hematuria or proteinuria. HRS is potentially reversible with liver transplantation or vasoconstrictor drugs. The condition carries a poor prognosis with high mortality rates, particularly in patients with advanced cirrhosis. The latest management for HRS involves a combination of pharmacological and non-pharmacological interventions, aiming to improve renal function and reduce the risk of mortality. Pharmacological treatments include vasoconstrictors, such as terlipressin and midodrine, and albumin infusion, which have been shown to improve renal function and reduce mortality in HRS patients. Non-pharmacological interventions, including invasive procedures such as transjugular intrahepatic portosystemic shunt (TIPS), plasma exchange, liver transplantation, and renal replacement therapy, may also be considered. Though TIPS has been shown to be effective in improving renal function in HRS patients, liver transplantation remains at the top of the consideration for the treatment of end-stage liver disease and HRS. Recent studies have placed importance on early recognition and prompt intervention in HRS patients, as delaying treatment can result in poorer outcomes. Although there are numerous reviews that summarize various aspects of HRS, the recent advancements in the management and pathophysiology of HRS are still insufficient. Therefore, in this review, we summarized a brief pathophysiology and highlighted recent advancements in the management of HRS with a quick review of the latest articles.
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Affiliation(s)
- Pooja Roy
- Internal Medicine, Harlem Hospital Center, New York, USA
| | - Naofel Minhaz
- Internal Medicine, Dhaka Medical College, Dhaka, BGD
| | | | | | - Tasniem Tasha
- Internal Medicine, Rajshahi Medical College, Rajshahi, BGD
| | | | | | - Farhana Alam
- Internal Medicine, Chittagong Medical College, Chittagong, BGD
| | - Shamima A Nila
- Internal Medicine, Cumilla Medical College and Hospital, Cumilla, BGD
| | - Janifa Akter
- Internal Medicine, Gonoshasthaya Samaj Vittik Medical College, Dhaka, BGD
- Internal Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, BGD
| | - Sharmin Akter
- Internal Medicine, Shaheed Ziaur Rahman Medical College, Bogura, BGD
| | - Shammo Biswas
- Internal Medicine, Sir Salimullah Medical College Mitford Hospital, Dhaka, BGD
| | - Nigar Sultana
- Internal Medicine, Sir Salimullah Medical College Mitford Hospital, Dhaka, BGD
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20
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Coxeter-Smith C, Al-Adhami A, Alrubaiy L. The Usefulness of Mayo End-stage Liver Disease (MELD) and MELD-Sodium (MELD-Na) Scores for Predicting Mortality in Cirrhotic Patients With Spontaneous Bacterial Peritonitis. Cureus 2023; 15:e38343. [PMID: 37143642 PMCID: PMC10151207 DOI: 10.7759/cureus.38343] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/30/2023] [Indexed: 05/06/2023] Open
Abstract
BACKGROUND Spontaneous bacterial peritonitis (SBP) is a common infection in patients with cirrhosis and ascites. Currently, the accuracy of the model for end-stage liver disease (MELD) and MELD-sodium (MELD-Na) as prognostic scores in this cohort is unclear. This study aimed to evaluate and compare the accuracy of MELD and MELD-Na for predicting 90-day mortality and determine whether the mortality risk estimates they provide accurately reflect the poor prognosis of patients with SBP Methods: Patients with cirrhosis and SBP were retrospectively identified from ascitic fluid samples sent for microscopy, culture and sensitivity analysis (1/1/18-31/12/20) and a previous audit. MELD and MELD-Na scores at diagnosis were calculated and associations with 90-day mortality were assessed using univariate analysis. Receiver operator characteristic curves were compared, and standardised mortality ratios (SMRs) were calculated by comparing the number of deaths observed to the number predicted by MELD and MELD-Na. RESULTS Of the 567 patients identified, 15 patients with cirrhosis and SBP were included. The 90-day mortality rate was 66.7% (10/15). Only concurrent hyponatremia (<135mmol/L) was associated with mortality (6/10 non-survivors vs 0/5 survivors, p=0.04). The difference in MELD and MELD-Na's C-statistic was not significant: 0.66 (95% Cl:0.35-0.98) vs 0.74 (95% Cl:0.47-1.0) respectively (p=0.72). Patients with a MELD-Na >18.5 had significantly higher 90-day mortality than patients with MELD-Na ≤18.5 (88.9% (8/9) vs. 33.3% (2/6), p=0.05). The SMR (95% Cl) for each MELD decile evaluated was 33.3 (0-79.5), 11.1 (0.2-22.0) and 3.4 (0-7.0) for scores ≤9,10-19 and 20-29 respectively. For each MELD-Na tertile, these were: 25 (0-59.6), 5.2 (0.1-10.3) and 2.7 (0.1-8.1) for scores <17,17-26, ≥27 respectively. CONCLUSION In a small cohort of patients with cirrhosis and SBP, the MELD's accuracy in predicting 90-day mortality was limited. MELD-Na's accuracy was higher but not significantly. Both scores consistently underestimated participants' mortality, therefore future studies could evaluate the accuracy of alternative prognostic scores in this patient group.
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Affiliation(s)
| | - Ali Al-Adhami
- Gastroenterology and Hepatology, St Mark's Hospital, London, GBR
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21
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Recent Developments in the Evaluation and Management of Cardiorenal Syndrome: A Comprehensive Review. Curr Probl Cardiol 2023; 48:101509. [PMID: 36402213 DOI: 10.1016/j.cpcardiol.2022.101509] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 11/11/2022] [Indexed: 11/18/2022]
Abstract
Cardiorenal syndrome (CRS) is an increasingly recognized diagnostic entity associated with high morbidity and mortality among acutely ill heart failure (HF) patients with acute and/ or chronic kidney diseases (CKD). While traditionally viewed as a state of decline in glomerular filtration rate (GFR) due to decreased renal perfusion, mainly due to therapeutic interventions to relieve congestive in HF, recent insights into the underlying pathophysiologic mechanisms of CRS led to a broader definition and further classification of CRS into 5 distinct types. In this comprehensive review, we discuss the classification of CRS, highlighting the underlying common pathogenetic pathways of heart failure and kidney injury, including increased congestion, neurohormonal dysregulation, oxidative stress as well as inflammation, and cytokine storm that are particularly evident in COVID-19 patients with multiorgan failure and also in those with other disorders including sepsis, systemic lupus erythematosus and amyloidosis. In this review we also present the recent advances in the diagnostic strategies of CRS including cardiac and renal biomarkers as well as advanced cardiac and renal imaging techniques that are available to aid in the diagnosis as well as in the prognostication of this disorder. Finally, we discuss the various therapeutic options available to-date, including fluid optimization, hemofiltration, renal replacement therapy as well as the role of SGLT2 inhibitors in light of recent data from RCTs. It is important to note that, CRS population are either excluded or underrepresented, at best, in major RCTs and therefore, therapeutic recommendations are largely extrapolated from HF and CKD clinical trials.
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22
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Lee S, Saffo S. Evolution of care in cirrhosis: Preventing hepatic decompensation through pharmacotherapy. World J Gastroenterol 2023; 29:61-74. [PMID: 36683719 PMCID: PMC9850948 DOI: 10.3748/wjg.v29.i1.61] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 10/22/2022] [Accepted: 12/14/2022] [Indexed: 01/04/2023] Open
Abstract
Cirrhosis is a leading cause of morbidity and mortality, impacting more than 120 million people worldwide. Although geographic differences exist, etiologic factors such as alcohol use disorder, chronic viral hepatitis infections, and non-alcoholic fatty liver disease are prevalent in nearly every region. Historically, significant effort has been devoted to modifying these risks to prevent disease progression. Nevertheless, more than 11% of patients with compensated cirrhosis experience hepatic decompensation each year. This transition signifies the most important prognostic factor in the natural history of the disease, corresponding to a decline in median survival to below 2 years. Over the past decade, the need for pharmacotherapies aimed at reducing the risk for hepatic decompensation has been emphasized, and non-selective beta-blockers have emerged as the most effective option to date. However, a critical therapeutic gap still exists, and additional therapies have been proposed, including statins, rifaximin, and sodium-glucose cotransporter-2 inhibitors. Based on the results of innovative retrospective analyses and small-scale prospective trials, these pharmacotherapies represent promising options, but further studies, including randomized controlled trials, are necessary before they can be incorporated into clinical use. This report highlights the potential impact of these agents and others in preventing hepatic decompensation and discusses how this paradigm shift may pave the way for guideline-directed medical therapy in cirrhosis.
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Affiliation(s)
- Seohyuk Lee
- Department of Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT 06520-8019, United States
| | - Saad Saffo
- Department of Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT 06520-8019, United States
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Wu HHL, Athwal VS, Kalra PA, Chinnadurai R. COVID-19 and hepatorenal syndrome. World J Gastroenterol 2022; 28:5666-5678. [PMID: 36338894 PMCID: PMC9627428 DOI: 10.3748/wjg.v28.i39.5666] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 09/21/2022] [Accepted: 10/02/2022] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a highly infectious disease which emerged into a global pandemic. Although it primarily causes respiratory symptoms for affected patients, COVID-19 was shown to have multi-organ manifestations. Elevated liver enzymes appear to be commonly observed during the course of COVID-19, and there have been numerous reports of liver injury secondary to COVID-19 infection. It has been established that patients with pre-existing chronic liver disease (CLD) are more likely to have poorer outcomes following COVID-19 infection compared to those without CLD. Co-morbidities such as diabetes, hypertension, obesity, cardiovascular and chronic kidney disease frequently co-exist in individuals living with CLD, and a substantial population may also live with some degree of frailty. The mechanisms of how COVID-19 induces liver injury have been postulated. Hepatorenal syndrome (HRS) is the occurrence of kidney dysfunction in patients with severe CLD/fulminant liver failure in the absence of another identifiable cause, and is usually a marker of severe decompensated liver disease. Select reports of HRS following acute COVID-19 infection have been presented, although the risk factors and pathophysiological mechanisms leading to HRS in COVID-19 infection or following COVID-19 treatment remain largely unestablished due to the relative lack and novelty of published data. Evidence discussing the management of HRS in high-dependency care and intensive care contexts is only emerging. In this article, we provide an overview on the speculative pathophysiological mechanisms of COVID-19 induced HRS and propose strategies for clinical diagnosis and management to optimize outcomes in this scenario.
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Affiliation(s)
- Henry H L Wu
- Renal Research, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney 2065, New South Wales, Australia
| | - Varinder S Athwal
- Faculty of Biology, Medicine & Health (Division of Diabetes, Metabolism & Gastroenterology), The University of Manchester, Manchester M13 9PL, United Kingdom
| | - Philip A Kalra
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, United Kingdom
| | - Rajkumar Chinnadurai
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, United Kingdom
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24
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Prognostic implications of systolic function in patients with cirrhosis. GASTROENTEROLOGÍA Y HEPATOLOGÍA 2022; 46:446-454. [DOI: 10.1016/j.gastrohep.2022.10.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 09/15/2022] [Accepted: 10/10/2022] [Indexed: 11/09/2022]
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25
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Pelayo J, Lo KB, Sultan S, Quintero E, Peterson E, Salacupa G, Zanoria MA, Guarin G, Helfman B, Sanon J, Mathew R, Yazdanyar A, Navarro V, Pressman G, Rangaswami J. Invasive hemodynamic parameters in patients with hepatorenal syndrome. IJC HEART & VASCULATURE 2022; 42:101094. [PMID: 36032268 PMCID: PMC9399284 DOI: 10.1016/j.ijcha.2022.101094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 06/28/2022] [Accepted: 07/17/2022] [Indexed: 11/30/2022]
Abstract
Background Hepatorenal syndrome (HRS), a form of kidney dysfunction frequent in cirrhotic patients, is characterized by low filling pressures and impaired kidney perfusion due to peripheral vasodilation and reduced effective circulatory volume. Cardiorenal syndrome (CRS), driven by renal venous hypertension and elevated filling pressures, is a separate cause of kidney dysfunction in cirrhotic patients. The two entities, however, have similar clinical phenotypes. To date, limited invasive hemodynamic data are available to help distinguish the primary forces behind worsened kidney function in cirrhotic patients. Objective Our aim was to analyze invasive hemodynamic profiles and kidney outcomes in patients with cirrhosis who met criteria for HRS. Methods We conducted a single center retrospective study among cirrhotic patients with worsening kidney function admitted for liver transplant evaluation between 2010 and 2020. All met accepted criteria for HRS and underwent concurrent right heart catheterization (RHC). Results 127 subjects were included. 79 had right atrial pressure >10 mmHg, 79 had wedge pressure >15 mmHg, and 68 had both. All patients with elevated wedge pressure were switched from volume loading to diuretics resulting in significant reductions between admission and post diuresis creatinine values (2.0 [IQR 1.5–2.8] vs 1.5 [IQR 1.2–2.2]; p = 0.003). Conclusion 62% of patients diagnosed with HRS by clinical criteria have elevated filling pressures. Improvement of renal function after diuresis suggests the presence of CRS physiology in these patients. Invasive hemodynamic data profiling can lead to meaningful change in management of cirrhotic patients with worsened kidney function, guiding appropriate therapies based on filling pressures.
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Affiliation(s)
- Jerald Pelayo
- Department of Medicine, Einstein Medical Center, Philadelphia, PA, United States
- Corresponding author at: 5501 Old York Road, Philadelphia, PA 19141, United States.
| | - Kevin Bryan Lo
- Department of Medicine, Einstein Medical Center, Philadelphia, PA, United States
| | - Sahar Sultan
- Department of Medicine, Einstein Medical Center, Philadelphia, PA, United States
| | - Eduardo Quintero
- Department of Medicine, Einstein Medical Center, Philadelphia, PA, United States
| | - Eric Peterson
- Department of Medicine, Einstein Medical Center, Philadelphia, PA, United States
| | - Grace Salacupa
- Department of Medicine, Einstein Medical Center, Philadelphia, PA, United States
| | | | - Geneva Guarin
- Department of Medicine, Einstein Medical Center, Philadelphia, PA, United States
| | - Beth Helfman
- Department of Medicine, Einstein Medical Center, Philadelphia, PA, United States
| | - Julien Sanon
- Department of Emergency and Hospital Medicine, Lehigh Valley Hospital-Cedar Crest, Allentown, PA, United States
- Morsani College of Medicine, University of South Florida, Tampa, FL, United States
| | - Roy Mathew
- Division of Nephrology, VA Health Care System, Loma Linda University, CA, United States
| | - Ali Yazdanyar
- Department of Emergency and Hospital Medicine, Lehigh Valley Hospital-Cedar Crest, Allentown, PA, United States
- Morsani College of Medicine, University of South Florida, Tampa, FL, United States
| | - Victor Navarro
- Department of Medicine, Einstein Medical Center, Philadelphia, PA, United States
- Division of Liver Disease and Transplantation, Einstein Medical Center, Philadelphia, PA, United States
| | - Gregg Pressman
- Department of Medicine, Einstein Medical Center, Philadelphia, PA, United States
- Division of Cardiology, Einstein Medical Center, Philadelphia, PA, United States
| | - Janani Rangaswami
- Department of Medicine, George Washington University, Washington, DC, United States
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26
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Pomej K, Scheiner B, Balcar L, Nussbaumer RJ, Weinzierl J, Paternostro R, Simbrunner B, Bauer D, Pereyra D, Starlinger P, Stättermayer AF, Pinter M, Trauner M, Quehenberger P, Reiberger T, Mandorfer M. Clinical significance of substantially elevated von Willebrand factor antigen levels in patients with advanced chronic liver disease. Dig Liver Dis 2022; 54:1376-1384. [PMID: 35871985 DOI: 10.1016/j.dld.2022.06.010] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 06/01/2022] [Accepted: 06/15/2022] [Indexed: 12/29/2022]
Abstract
BACKGROUND Von Willebrand factor antigen (VWF) is a non-invasive marker for clinically significant portal hypertension (HVPG≥10 mmHg) and confers HVPG-independent prognostic information. While quantification of increased VWF-levels is not relevant in the context of von Willebrand disease, highly elevated VWF may be of clinical significance in ACLD. Thus, we have modified our analytical approach to quantify very high VWF-levels (i.e.,>420%) and investigated their prognostic value. METHODS Patients undergoing HVPG-measurement at the Vienna Hepatic Hemodynamic Lab with evidence of ACLD and information on VWF were considered. Clinical stages (CS) were defined as follows: Probable compensated ACLD (cACLD): LSM≥10kPa&HVPG<6 mmHg; 0: cACLD&6-9 mmHg; 1: cACLD&HVPG≥10 mmHg; 2: bleeding; 3: non-bleeding decompensation; 4: ≥2 decompensations. RESULTS 124 (16%) of 793 patients had VWF>420%. The proportion of VWF>420% increased with disease severity (probable cACLD-0: 5(4%) vs. 1: 22(10%) vs. 2-4: 97(23%),p ≤ 0.001) as well as across HVPG (<6mmHg: 1(2%) vs. 6-9: 6(6%) vs. 10-15: 17(9%) vs. ≥16: 100(22%),p ≤ 0.001) and MELD (<10: 17(6%) vs. 10-14: 27(10%) vs. ≥15: 79(32%),p ≤ 0.001) strata. In patients with VWF>420%, median VWF was 533 (IQR:466-611)% and VWF was unrelated to HVPG (Spearman's ρ=0.139,p = 0.123), but showed direct correlations of weak/moderate strength with MELD (ρ=0.336,p < 0.001) and CRP (ρ=0.286,p = 0.001). In the subgroup with VWF>420%, VWF was predictive of decompensation/liver-related mortality (VWF per 10%; hazard ratio (HR): 1.02(95% confidence interval (95%CI): 1.01-1.04),p = 0.008, even after adjusting for other factors (VWF per 10%; adjusted HR: 1.02(95%CI: 1.00-1.05),p = 0.031). CONCLUSION The proportion of patients with substantially elevated VWF values steadily increases with disease progression. While VWF is not reflective of HVPG in these patients, it is correlated with hepatic dysfunction and systemic inflammation. Importantly, quantification of high values provides prognostic information.
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Affiliation(s)
- Katharina Pomej
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Bernhard Scheiner
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Lorenz Balcar
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Rosa Johanna Nussbaumer
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Johanna Weinzierl
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Rafael Paternostro
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Benedikt Simbrunner
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - David Bauer
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - David Pereyra
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Patrick Starlinger
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Albert Friedrich Stättermayer
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Matthias Pinter
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
| | - Peter Quehenberger
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Christian Doppler Laboratory for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria.
| | - Mattias Mandorfer
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria
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Nabilou P, Danielsen KV, Kimer N, Hove JD, Bendtsen F, Møller S. Blunted cardiovascular effects of beta-blockers in patients with cirrhosis: Relation to severity? PLoS One 2022; 17:e0270603. [PMID: 35763518 PMCID: PMC9239488 DOI: 10.1371/journal.pone.0270603] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Accepted: 06/13/2022] [Indexed: 11/22/2022] Open
Abstract
Aims Patients with cirrhosis and portal hypertension are at high risk of developing complications such as variceal hemorrhage, ascites, and cardiac dysfunction, the latter of which is known as cirrhotic cardiomyopathy. Since non-selective beta-blockers (NSBB) may aggravate hemodynamic complications we investigated the effect of real-time propranolol infusion on cardiac function in patients with varying degrees of cirrhosis. Methods Thirty-eight patients with Child-Pugh A (n = 17), B (n = 17) and C (n = 4) underwent liver vein catheterization and cardiac magnetic resonance imaging. We assessed the effect of real-time propranolol infusion on the hepatic venous pressure gradient, cardiac index, stroke volume, ejection fraction, heart rate, and contractility. Results Nineteen patients were classified as responders to beta-blocker therapy. In pooling Child-Pugh B and C patients, the reduction in cardiac index by beta-blockade was weaker than in Child-Pugh A patients (-8.5% vs. -20.5%, p = 0.043). The effect of NSBB on portal pressure was inversely correlated to changes in the left atrium where the left atrial volume changed by 4 mL±18 in responders compared to 15 mL±11 in non-responders (p = 0.03). Finally, the baseline ejection fraction correlated inversely with the reduction in portal pressure (r = -0.39, p = 0.02). Conclusion We found the effect of beta-blockade on cardiac index in patients with advanced cirrhosis to be less potent than in patients with early cirrhosis, indicating that underlying cirrhotic cardiomyopathy increases, and the cardiac compensatory reserve becomes more compromised, with disease progression. The differential effects of beta-blockade in the left atrium may be used to predict the effect of beta-blockers on portal pressure, but further studies are needed to investigate this possibility.
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Affiliation(s)
- Puria Nabilou
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
- * E-mail:
| | - Karen Vagner Danielsen
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Nina Kimer
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Jens Dahlgaard Hove
- Department of Cardiology, Copenhagen University Hospital, Hvidovre, Denmark
- Department of Clinical Medicine, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Flemming Bendtsen
- Gastro Unit, Medical Division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
- Department of Clinical Medicine, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Søren Møller
- Department of Clinical Medicine, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
- Dept. Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, København, Denmark
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Propranolol vs. band ligation for primary prophylaxis of variceal hemorrhage in cirrhotic patients with ascites: a randomized controlled trial. Hepatol Int 2022; 16:944-953. [DOI: 10.1007/s12072-022-10361-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 05/07/2022] [Indexed: 11/04/2022]
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Buccheri S, Da BL. Hepatorenal Syndrome: Definitions, Diagnosis, and Management. Clin Liver Dis 2022; 26:181-201. [PMID: 35487604 DOI: 10.1016/j.cld.2022.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Hepatorenal syndrome (HRS) is a hemodynamically driven process mediated by renal dysregulation and inflammatory response. Albumin, antibiotics, and β-blockers are among therapies that have been studied in HRS prevention. There are no Food and Drug Administration-approved treatments for HRS although multiple liver societies have recommended terlipressin as first-line pharmacotherapy. Renal replacement therapy is the primary modality used to bridge to definitive therapy with orthotopic liver transplant or simultaneous liver-kidney transplant. Advances in our understanding of HRS pathophysiology and emerging therapeutic modalities are needed to change outcomes for this vulnerable population.
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Affiliation(s)
- Sebastiano Buccheri
- Department of Internal Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, 400 Community Drive, Manhasset, NY 11030, USA
| | - Ben L Da
- Department of Internal Medicine, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases & Transplantation, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, 400 Community Drive, Manhasset, NY 11030, USA.
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30
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Taher MY, El-Hadidi A, El-Shendidi A, Sedky A. Soluble CD163 for Prediction of High-Risk Esophageal Varices and Variceal Hemorrhage in Patients with Liver Cirrhosis. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2022; 29:82-95. [PMID: 35497666 PMCID: PMC8995632 DOI: 10.1159/000516913] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Accepted: 04/22/2021] [Indexed: 02/18/2025]
Abstract
INTRODUCTION Activation of hepatic macrophages in liver disease is pathogenically related to portal hypertension (PH). Soluble CD163 (sCD163) is shed in blood by activated macrophages and may predict PH progression noninvasively. This study was designed to investigate the relation of serum sCD163 to the grade and bleeding risk of esophageal varices (EV) and its role for prediction of variceal hemorrhage (VH). METHODS The study included cirrhotic patients divided into 3 groups: patients who presented with acute upper gastrointestinal bleeding (UGIB) proved to originate from EV on endoscopy, patients without any history of UGIB but who revealed EV on surveillance endoscopy, and patients without endoscopic evidence of varices. Variceal grade and risk signs and bleeding stigmata were noted simultaneously with measurement of serum sCD163 concentration. RESULTS Serum sCD163 concentration showed a significant increase in cirrhotic patients compared to healthy subjects (p < 0.001) with a stepwise increase among the group without varices, nonbleeder group, and bleeder group sequentially. Serum sCD163 levels correlated positively with the variceal grade and risk signs in both the bleeder and nonbleeder groups (p = 0.002, p < 0.001 and p = 0.004, p < 0.001, respectively). Serum sCD163 at a cutoff value of 3.6 mg/L performed significantly for prediction of EV presence (AUC = 0.888). Serum sCD163 at a cutoff value >4 mg/L significantly predicted large-size and high-risk EV (AUC = 0.910 and AUC = 0.939, respectively) and the index bleed risk (AUC = 0.977). Serum sCD163 at a cutoff value >4.05 mg/L modestly discriminated bleeding EV from those that had never bled (AUC = 0.811). CONCLUSIONS Serum sCD163 levels accurately predicted high-grade and high-risk EV and could help plan for primary prophylaxis. However, it modestly identified VH occurrence, and endoscopy would be required to make a definitive diagnosis.
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Affiliation(s)
- Mohamed Yousri Taher
- Department of Internal Medicine (Hepatology Division), Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Abeer El-Hadidi
- Department of Clinical and Chemical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Assem El-Shendidi
- Department of Internal Medicine (Hepatology Division), Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Ahmed Sedky
- Department of Internal Medicine (Hepatology Division), Faculty of Medicine, Alexandria University, Alexandria, Egypt
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Anikhindi SA, Ranjan P, Kumar M, Mohan R. A Prospective Study of Prevalence and Predictors of Cirrhotic Cardiomyopathy and Its Role in Development of Hepatorenal Syndrome. J Clin Exp Hepatol 2022; 12:853-860. [PMID: 35677509 PMCID: PMC9168708 DOI: 10.1016/j.jceh.2021.11.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 11/09/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIMS Cirrhotic cardiomyopathy (CCM) is a term used to collectively describe abnormal structural and functional changes in heart of patients with cirrhosis. The present study was undertaken to find the prevalence of CCM in patients with liver cirrhosis and its predictors. We also followed these patients to evaluate the role of CCM in the development of hepatorenal syndrome (HRS). MATERIALS & METHODS This was a prospective study carried out in department of Gastroenterology, Sir Ganga Ram hospital, New Delhi. A total of 104 patients with liver cirrhosis were included. Liver cirrhosis was diagnosed on basis of clinical, biochemical, and imaging features. CCM was defined based on echocardiography. Dobutamine stress echocardiography and hepatic venous pressure gradient (HVPG) were performed in patients who gave consent. HRS was defined as per standard criteria. Patients with CCM were followed for development of HRS. RESULTS Fifty (48%) patients were diagnosed with CCM. All patients had diastolic dysfunction, and none had systolic dysfunction. Median age of patients with CCM was significantly higher (59 [31-78 y] vs. 52 [24-70 y], P < 0.05). Severity of liver disease (Child Turcotte Pugh score and model for end-stage liver disease score) and portal pressures (HVPG) did not differ in patients with or without CCM. Patients with CCM did not have increased incidence of HRS at the end of 6-month follow-up study. CONCLUSION The presence of CCM was not related with the severity of liver dysfunction or portal pressures. Age was a significant determinant of CCM. Diastolic cardiac dysfunction does not influence the occurrence of HRS.
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Key Words
- 2D echo, two-dimensional echocardiography
- CCM, cirrhotic cardiomyopathy
- CTP, Child Turcotte Pugh
- DD, diastolic dysfunction
- DSE, dobutamine stress echocardiography
- FHVP, free hepatic venous pressure
- HRS, hepatorenal syndrome
- HVPG, hepatic venous pressure gradient
- LVEF, left ventricular ejection fraction
- MELD, model for end-stage liver disease
- TDI, tissue Doppler imaging
- cardiomyopathy
- cirrhosis
- diastolic cardiac dysfunction
- hepatorenal syndrome
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Affiliation(s)
- Shrihari A. Anikhindi
- Institute of Liver, Gastroenterology and Pancreaticobiliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Piyush Ranjan
- Institute of Liver, Gastroenterology and Pancreaticobiliary Sciences, Sir Ganga Ram Hospital, New Delhi, India,Address for correspondence: Piyush Ranjan, Institute of Liver, Gastroenterology and Pancreaticobiliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, 110 060, New Delhi, India.
| | - Mandhir Kumar
- Institute of Liver, Gastroenterology and Pancreaticobiliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Rajat Mohan
- Department of Cardiology, Sir Ganga Ram Hospital, New Delhi, India
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Jachs M, Reiberger T. Non-selective Beta Blockers in Liver Cirrhosis. PHARMACOTHERAPY FOR LIVER CIRRHOSIS AND ITS COMPLICATIONS 2022:127-140. [DOI: 10.1007/978-981-19-2615-0_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Diastolic Dysfunction Is a Predictor of Poor Survival in Patients with Decompensated Cirrhosis. Int J Hepatol 2021; 2021:5592376. [PMID: 34900353 PMCID: PMC8660240 DOI: 10.1155/2021/5592376] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 11/17/2021] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Left ventricular diastolic dysfunction (LVDD) appears to be the earliest cardiac disturbance in cirrhosis patients. There are many previous reports reporting the significance of severity of LVDD on the outcome of liver transplantation or TIPS insertion, a few Indian studies have addressed the role of LVDD on survival in decompensated cirrhosis. The objective of this study is to assess the effect of LVDD on the survival of decompensated cirrhotic patients. METHODS We prospectively evaluated 92 decompensated cirrhotic patients from April 2015 to March 2017 at IMS and SUM Hospital, Bhubaneswar, India. 2D echocardiography with tissue Doppler imaging was used to evaluate cardiac function, as per the American society of echocardiography guidelines. The primary endpoint was to evaluate the effect of LVDD on overall mortality. RESULTS Ninety-two decompensated cirrhotic patients were evaluated in this prospective cohort study. Twenty-eight out of 92 patients (30%) died due to liver-related complications after a follow-up of 24 months. The decompensated cirrhotic patients with MELD score ≥ 15 had a significantly higher E/e' ratio (11.94 ± 4.24 vs. 8.74 ± 3.32, p < 0.001) suggesting severe LV dysfunction in advanced cirrhosis. Patients with E/e' ratio > 10 had significantly higher MELD score and Child-Pugh score (19.88 ± 7.72 vs. 14.31 ± 5.83; 10.25 ± 1.74 vs. 9.02 ± 1.74, p < 0.01, respectively) as compared to theE/e' ratio < 10 group. In Cox proportional hazard multivariate analysis, E/e' ≥ 10 (HR 2.72, 95% CI 1.07-6.9, p = 0.03) and serum albumin (HR 0.32, 95% CI 0.14-0.7, p < 0.01) were found to be independent predictors of mortality in decompensated cirrhotic patients. CONCLUSION : The presence of LVDD and low serum albumin were independent predictors of mortality in decompensated cirrhotic patients. Hence, LVDD is an indicator of advanced cirrhosis and mortality.
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Haque LY, Garcia‐Tsao G. A Historical Overview of Spontaneous Bacterial Peritonitis: From Rare to Resistant. Clin Liver Dis (Hoboken) 2021; 18:63-75. [PMID: 34745584 PMCID: PMC8555457 DOI: 10.1002/cld.1122] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 03/26/2021] [Indexed: 02/04/2023] Open
Abstract
Content available: Author Audio Recording.
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Affiliation(s)
- Lamia Y. Haque
- Section of Digestive DiseasesYale School of MedicineNew HavenCT
- Department of MedicineYale School of MedicineNew HavenCT
| | - Guadalupe Garcia‐Tsao
- Section of Digestive DiseasesYale School of MedicineNew HavenCT
- Department of MedicineYale School of MedicineNew HavenCT
- Digestive DiseasesVeterans Administration Connecticut Healthcare SystemWest HavenCT
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Yazdanyar A, Lo KB, Pelayo J, Sanon J, Romero A, Quintero E, Ahluwalia A, Gupta S, Sankaranarayanan R, Mathew R, Rangaswami J. Association Between Cirrhosis and 30-Day Rehospitalization After Index Hospitalization for Heart Failure. Curr Probl Cardiol 2021; 47:100993. [PMID: 34571101 DOI: 10.1016/j.cpcardiol.2021.100993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 09/14/2021] [Indexed: 11/18/2022]
Abstract
There are limited data on clinical outcomes in patients re-admitted with decompensated heart failure (HF) with concomitant liver cirrhosis. We conducted a cross sectional analysis of the Nationwide Readmissions Database (NRD) years 2010 thru 2012. An Index admission was defined as a hospitalization for decompensated heart failure among persons aged ≥ 18 years with an alive discharge status. The main outcome was 30 - day all-cause rehospitalization. Survey logistic regression provided the unadjusted and adjusted odds of 30 - day rehospitalization among persons with and without cirrhosis, accounting for age, gender, kidney dysfunction and other comorbidities. There were 2,147,363 heart failure (HF) hospitalizations among which 26,156 (1.2%) had comorbid cirrhosis. Patients with cirrhosis were more likely to have a diagnosis of acute kidney injury (AKI) during their index hospitalization (18.4% vs 15.2%). There were 469,111 (21.9%) patients with readmission within 30 - days. The adjusted odds of a 30 - day readmission was significantly higher among patients with cirrhosis compared to without after adjusting for comorbid conditions (adjusted Odds Ratio [aOR], 1.3; 95% Confidence Interval [CI}: 1.2 to 1.4). The relative risk of 30 - day readmission among those with cirrhosis but without renal disease (aOR, 1.3; 95% CI: 1.3 to 1.3) was lower than those with both cirrhosis and renal disease (aOR, 1.8; 95% CI: 1.6 to 2.0) when compared to persons without either comorbidities. Risk of 30 - day rehospitalization was significantly higher among patients with heart failure and underlying cirrhosis. Concurrent renal dysfunction among patients with cirrhosis hospitalized for decompensated HF was associated with a greater odds of rehospitalization.
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Affiliation(s)
- Ali Yazdanyar
- Department of Emergency and Hospital Medicine, Lehigh Valley Hospital-Cedar Crest, Allentown, PA; Morsani College of Medicine, University of South Florida, Tampa, FL
| | - Kevin Bryan Lo
- Department of Medicine, Einstein Medical Center, Philadelphia, PA, USA
| | - Jerald Pelayo
- Department of Medicine, Einstein Medical Center, Philadelphia, PA, USA.
| | - Julien Sanon
- Department of Emergency and Hospital Medicine, Lehigh Valley Hospital-Cedar Crest, Allentown, PA
| | - Ardel Romero
- Department of Medicine, Einstein Medical Center, Philadelphia, PA, USA
| | - Eduardo Quintero
- Department of Medicine, Einstein Medical Center, Philadelphia, PA, USA
| | - Arjan Ahluwalia
- Department of Medicine, Lehigh Valley Hospital-Cedar Crest, Allentown, PA
| | - Shuchita Gupta
- University Advanced Heart Failure Center, University Heart and Vascular Institute, Augusta GA
| | - Rajiv Sankaranarayanan
- Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool Heart & Chest Hospital, Liverpool, UK
| | - Roy Mathew
- Division of Nephrology, Columbia VA Health Care System, Columbia, SC, USA
| | - Janani Rangaswami
- Division of Nephrology, George Washington University School of Medicine, Washington DC, USA
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Rey I, Effendi-Ys R. Association Between Serum IL-6, IL-10, IL-12, and IL-23 Levels and Severity of Liver Cirrhosis. Med Arch 2021; 75:199-203. [PMID: 34483450 PMCID: PMC8385729 DOI: 10.5455/medarh.2021.75.199-203] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 06/15/2021] [Indexed: 11/03/2022] Open
Abstract
Background Liver cirrhosis contributes to high liver-related mortality globally. Systemic inflammation mediated by immune cells contributes to the progression of liver cirrhosis. Growing evidence shows that several pro- and anti-inflammatory cytokines might have an important role in liver cirrhosis. Objective To evaluate the association between serum IL-6, IL-10, IL-12, and IL-23 levels and severity of liver cirrhosis. Methods This observational study was carried out at the Department of Internal Medicine, Universitas Sumatera Utara, Indonesia from March 2018 to August 2019. The severity of liver cirrhosis was assessed by using the Child-Pugh score. IL-6, IL-10, IL-12, and IL-23 levels, hepatitis and renal function were measured in all study subjects. Independent t-test and Mann-Whitney tests were conducted to observe differences between groups. Results A total of 78 liver cirrhosis patients were enrolled, mean age was 50.6±11.4. Median serum IL-6, IL-10, IL-12, and IL-23 levels were 24.5(2.6-46.4)pg/ml, 2.1(0.4-9.3)pg/ml, 3.5(1.4-20.8)pg/ml and 20.3(9.2-218)pg/ml, respectively. A higher IL-6 level was associated with more severe liver cirrhosis (p=0.001) and the presence of hepatic encephalopathy (p=0.018). Higher IL-23 level was found in patients with no hepatic encephalopathy (p=0.049). There was no association between serum cytokines levels and hepatitis viral infection status. Conclusion IL-6 is associated with the severity of liver cirrhosis.
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Affiliation(s)
- Imelda Rey
- Division of Gastroenterohepatology, Department of Internal Medicine, Universitas Sumatera Utara, Medan, Indonesia.,Haji Adam Malik General Hospital, Medan Indonesia
| | - Rustam Effendi-Ys
- Division of Gastroenterohepatology, Department of Internal Medicine, Universitas Sumatera Utara, Medan, Indonesia.,"dr. Pirngadi" General Hospital, Medan Indonesia
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Villanueva C, Albillos A, Genescà J, Garcia-Pagan JC, Brujats A, Calleja JL, Aracil C, Bañares R, Morillas RM, Poca M, Peñas B, Augustin S, Abraldes JG, Alvarado E, Torres F, Bosch J. Bacterial infections adversely influence the risk of decompensation and survival in compensated cirrhosis. J Hepatol 2021; 75:589-599. [PMID: 33905794 DOI: 10.1016/j.jhep.2021.04.022] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 03/25/2021] [Accepted: 04/12/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS The prognosis of compensated cirrhosis is good until decompensation. In decompensated cirrhosis, bacterial infections (BIs) are common and increase the risk of death. The incidence and prognostic implications of BIs in compensated cirrhosis are less-well characterized. This study aimed to assess whether BIs influence the risk of decompensation and survival in patients with compensated cirrhosis. METHODS This is a cohort study nested to the PREDESCI study, a double-blind, multicenter, randomized controlled trial designed to assess whether β-blockers could prevent decompensation of cirrhosis. Patients with compensated cirrhosis and hepatic venous pressure gradient ≥10 mmHg were included. Development of BIs during follow-up was prospectively registered. Using a competing-risk time-dependent regression analysis, we investigated whether BIs affect the risk of decompensation and survival. Decompensation was defined as development of ascites, bleeding or overt encephalopathy. RESULTS A total of 201 patients were randomized and followed for a median of 36 months (IQR 24-47 months); 34 patients (17%) developed BIs, which occurred before decompensation in 33 cases, and 29 (14%) developed ascites. Respiratory and urinary tract infections were the most frequent BIs. Decompensation occurred in 26% patients with BIs vs. 16% without BIs. Patients with BIs were at higher risk of decompensation (subdistribution hazard ratio [SHR] 2.93; 95% CI 1.02-8.42; p = 0.047) and of developing ascites (SHR 3.55; 95% CI 1.21-10.47; p = 0.022) than those without BIs. Risk of death was also higher in patients with BIs (subdistribution HR 6.93; 95% CI 2.64-18.18; p <0.001), although decompensation occurred before death in 71% of such cases. CONCLUSIONS BIs have a marked impact on the natural history of compensated cirrhosis, significantly increasing the risk of decompensation, mainly that of ascites, and increasing the risk of death, which usually occurs after decompensation. Our results suggest that BIs may constitute a target to prevent decompensation. LAY SUMMARY It is widely known that bacterial infections are common and increase the mortality risk in patients with decompensated cirrhosis. However, the relevance of bacterial infections in compensated cirrhosis has not been well studied. This study shows that in patients with compensated cirrhosis and clinically significant portal hypertension, bacterial infections occur as frequently as the development of ascites, which is the most frequent decompensating event. Bacterial infections increase the risk of progression to decompensation, mainly by increasing the risk of ascites, and also increase the risk of death, which usually occurs after decompensation. CLINICALTRIALS. GOV IDENTIFIER NCT01059396.
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Affiliation(s)
- Càndid Villanueva
- Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, 08025, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain.
| | - Agustín Albillos
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Madrid, Spain
| | - Joan Genescà
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Liver Unit, Department of Internal Medicine, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Spain
| | - Joan C Garcia-Pagan
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain(‡)
| | - Anna Brujats
- Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, 08025, Barcelona, Spain
| | - José L Calleja
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Hospital Universitario Puerta de Hierro, IDIPHIM, Universidad Autónoma de Madird, Madrid, Spain
| | - Carles Aracil
- Hospital Universitari Arnau de Vilanova, Lleida, Institut de Recerca Biomèdica (IRBLleida), Spain
| | - Rafael Bañares
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Hospital General Universitario Gregorio Marañón, IISGM, Universidad Complutense, Madrid, Spain
| | - Rosa M Morillas
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Liver Section, Hospital Universitari Germans Trias i Pujol, IGTP, Universitat Autònoma de Barcelona, Badalona, Spain
| | - María Poca
- Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, 08025, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
| | - Beatriz Peñas
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Madrid, Spain
| | - Salvador Augustin
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Liver Unit, Department of Internal Medicine, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Research (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Spain
| | - Juan G Abraldes
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain(‡); Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada
| | - Edilmar Alvarado
- Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, 08025, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
| | - Ferran Torres
- Medical Statistics Core Facility, IDIBAPS, Hospital Clinic, Barcelona, Spain; Biostatistics Unit, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Jaume Bosch
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain(‡); University Clinic for Visceral Surgery and Medicine, Inselspital, Bern University, Switzerland
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Liu PMF, de Carvalho ST, Fradico PF, Cazumbá MLB, Campos RGB, Simões E Silva AC. Hepatorenal syndrome in children: a review. Pediatr Nephrol 2021; 36:2203-2215. [PMID: 33001296 PMCID: PMC7527294 DOI: 10.1007/s00467-020-04762-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 08/01/2020] [Accepted: 09/05/2020] [Indexed: 02/07/2023]
Abstract
Hepatorenal syndrome (HRS) occurs in patients with cirrhosis or fulminant hepatic failure and is a kind of pre-renal failure due to intense reduction of kidney perfusion induced by severe hepatic injury. While other causes of pre-renal acute kidney injury (AKI) respond to fluid infusion, HRS does not. HRS incidence is 5% in children with chronic liver conditions before liver transplantation. Type 1 HRS is an acute and rapidly progressive form that often develops after a precipitating factor, including gastrointestinal bleeding or spontaneous bacterial peritonitis, while type 2 is considered a slowly progressive form of kidney failure that often occurs spontaneously in chronic ascites settings. HRS pathogenesis is multifactorial. Cirrhosis causes portal hypertension; therefore, stasis and release of vasodilator substances occur in the hepatic vascular bed, leading to vasodilatation of splanchnic arteries and systemic hypotension. Many mechanisms seem to work together to cause this imbalance: splanchnic vasodilatation; vasoactive mediators; hyperdynamic circulation states and subsequent cardiac dysfunction; neuro-hormonal mechanisms; changes in sympathetic nervous system, renin-angiotensin system, and vasopressin. In patients with AKI and cirrhosis, fluid expansion therapy needs to be initiated as soon as possible and nephrotoxic drugs discontinued. Once HRS is diagnosed, pharmacological treatment with vasoconstrictors, mainly terlipressin plus albumin, should be initiated. If there is no response, other options can include surgical venous shunts and kidney replacement therapy. In this regard, extracorporeal liver support can be a bridge for liver transplantation, which remains as the ideal treatment. Further studies are necessary to investigate early biomarkers and alternative treatments for HRS.
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Affiliation(s)
- Priscila Menezes Ferri Liu
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, UFMG, Avenida Alfredo Balena, 190, 2nd floor, #281 room, Belo Horizonte, Minas Gerais, 30130-100, Brazil
| | - Sarah Tayná de Carvalho
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, UFMG, Avenida Alfredo Balena, 190, 2nd floor, #281 room, Belo Horizonte, Minas Gerais, 30130-100, Brazil
| | - Pollyanna Faria Fradico
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, UFMG, Avenida Alfredo Balena, 190, 2nd floor, #281 room, Belo Horizonte, Minas Gerais, 30130-100, Brazil
| | - Maria Luiza Barreto Cazumbá
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, UFMG, Avenida Alfredo Balena, 190, 2nd floor, #281 room, Belo Horizonte, Minas Gerais, 30130-100, Brazil
| | - Ramon Gustavo Bernardino Campos
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, UFMG, Avenida Alfredo Balena, 190, 2nd floor, #281 room, Belo Horizonte, Minas Gerais, 30130-100, Brazil
| | - Ana Cristina Simões E Silva
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, UFMG, Avenida Alfredo Balena, 190, 2nd floor, #281 room, Belo Horizonte, Minas Gerais, 30130-100, Brazil.
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Transition to decompensation and acute-on-chronic liver failure: Role of predisposing factors and precipitating events. J Hepatol 2021; 75 Suppl 1:S36-S48. [PMID: 34039491 DOI: 10.1016/j.jhep.2020.12.005] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 12/08/2020] [Accepted: 12/08/2020] [Indexed: 12/13/2022]
Abstract
The transition from compensated to decompensated cirrhosis results from a complex interplay of predisposing and precipitating factors and represents an inflection point in the probability of a patient surviving. With the progression of cirrhosis, patients accumulate multiple disorders (e.g. altered liver architecture, portal hypertension, local and systemic inflammation, bacterial translocation, gut dysbiosis, kidney vasoconstriction) that predispose them to decompensation. On the background of these factors, precipitating events (e.g. bacterial infection, alcoholic hepatitis, variceal haemorrhage, drug-induced liver injury, flare of liver disease) lead to acute decompensation (ascites, hepatic encephalopathy, variceal bleeding, jaundice) and/or organ failures, which characterise acute-on-chronic liver failure. In this review paper, we will discuss the current hypotheses and latest evidences regarding predisposing and precipitating factors associated with the transition to decompensated liver disease.
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Jalan R, D'Amico G, Trebicka J, Moreau R, Angeli P, Arroyo V. New clinical and pathophysiological perspectives defining the trajectory of cirrhosis. J Hepatol 2021; 75 Suppl 1:S14-S26. [PMID: 34039485 DOI: 10.1016/j.jhep.2021.01.018] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 01/08/2021] [Accepted: 01/11/2021] [Indexed: 02/06/2023]
Abstract
Traditionally, the complications of cirrhosis, namely variceal bleeding, ascites and hepatic encephalopathy, were thought to result predominantly from circulatory dysfunction and altered organ perfusion arising as a result of portal hypertension. Over the past 20 years, large, international prospective studies have indicated the importance of systemic inflammation and organ immunopathology as additional determinants of organ dysfunction in cirrhosis, which not only manifests in the liver, brain, circulation and the kidneys, but also the immune system, gut, muscles, adrenal glands, reproductive organs, heart and lungs. This review provides an overview of the traditional and emerging concepts around the initiation and maintenance of organ dysfunction in cirrhosis and proposes a new paradigm based upon a better understanding of acute decompensation of cirrhosis. The interaction between the traditional concepts and the emerging perspectives remains a matter of great interest and the basis for future research.
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Affiliation(s)
- Rajiv Jalan
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; Liver Failure Group, Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, United Kingdom.
| | - Gennaro D'Amico
- Gastroenterology Unit, Ospedale Cervello and University of Palermo, Italy
| | - Jonel Trebicka
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; JW Goethe University Hospital, Frankfurt, Germany
| | - Richard Moreau
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; APHP, Hôpital Beaujon, Service d'Hépatologie, Clichy, France; Inserm, Université de Paris, Centre de Recherche sur L'Inflammation, Paris, France
| | - Paolo Angeli
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; University of Padova, Padova, Italy
| | - Vicente Arroyo
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain
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Helal EM, Sharaf-Eldin M, Abou El Azm AR, Badr Eldin NM, Dawoud MM, Abd-Elsalam S, Ziada DH. Hemodynamic Changes of Hepatic & Renal Vessels in Systemic Bacterial Infection with Fever in HCV Related Cirrhosis. Infect Disord Drug Targets 2021; 20:511-516. [PMID: 31057113 DOI: 10.2174/1871526519666190506102703] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 01/25/2019] [Accepted: 04/20/2019] [Indexed: 11/22/2022]
Abstract
OBJECTIVES To study the hemodynamic changes of hepatic & renal vessels in systemic bacterial infection with fever in HCV related cirrhosis with possible complications. METHODS Three groups of patients with systemic bacterial infection with fever were included in the study; group І included 15 patients with decompensated cirrhosis, group ІІ included 15 patients with compensated cirrhosis and group ІІІ included 10 patients without liver affection. Laboratory parameters and Doppler US of hepatic and renal vessels were evaluated during and after subsidence of fever in all patients. RESULTS Forty patients were enrolled in this prospective study. There were 22 male and 18 female patients. We found that the direction of blood flow in the portal and splenic veins was hepatopetal and the veins were non pulsatile in all cases with no change during and after subsidence of infection. There was no significant difference in portal or splenic vein diameters during and after subsidence of infection in the three studied groups. However, the mean values of portal and splenic veins peak velocities were significantly lower during infection in cirrhotic groups. The mean value of hepatic artery resistive index during fever was significantly higher than after fever in cirrhotic groups. Renal resistive and pulsatility indices were significantly higher during fever in cirrhotic groups. CONCLUSION Systemic bacterial infection with fever can affect hepatic haemodynamics leading to aggravation of portal hypertension and increasing the risk of complications as variceal bleeding and hepatic encephalopathy and can also affect renal haemodynamics with increased risk of renal impairment.
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Affiliation(s)
- Eman Mohammed Helal
- Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Mohamed Sharaf-Eldin
- Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
| | | | | | | | - Sherief Abd-Elsalam
- Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Dina Hazem Ziada
- Department of Tropical Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
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Jachs M, Reiberger T. Prevention of Variceal Bleeding and Rebleeding by Nonselective Beta-Blockers: A Tailored Approach. Clin Liver Dis 2021; 25:311-326. [PMID: 33838852 DOI: 10.1016/j.cld.2021.01.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Indexed: 01/31/2023]
Abstract
Nonselective beta-blockers represent the mainstay of medical therapy in the prophylaxis of variceal bleeding and rebleeding in patients with portal hypertension. Their efficacy has been demonstrated by numerous trials; however, there exist safety concerns in advanced disease, such as in patients with refractory ascites. Importantly, nonselective beta-blockers also exert nonhemodynamic beneficial effects that may contribute to a prolonged decompensation-free survival, as recently shown in the PREDESCI trial. This review summarizes the current evidence on nonselective beta-blocker therapy and proposes a tailored, patient-centered approach for the use of nonselective beta-blockers in patients with portal hypertension.
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Affiliation(s)
- Mathias Jachs
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria
| | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria; Vienna Hepatic Hemodynamic Lab, Medical University of Vienna, Vienna, Austria; Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, Vienna, Austria.
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Dourakis SP, Geladari E, Geladari C, Vallianou N. Cirrhotic Cardiomyopathy: The Interplay Between Liver and Cardiac Muscle. How Does the Cardiovascular System React When the Liver is Diseased? Curr Cardiol Rev 2021; 17:78-84. [PMID: 31072296 PMCID: PMC8142364 DOI: 10.2174/1573403x15666190509084519] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 04/21/2019] [Accepted: 04/22/2019] [Indexed: 12/03/2022] Open
Abstract
It is widely known that liver cirrhosis, regardless of the etiologies is accompanied by severe hemodynamic changes. The principal pathophysiological mechanisms are the hyperdynamic circulation with increased cardiac output, heart rate along with reduced systemic vascular resistance. Thus, counteractive mechanisms may develop that eventually lead to systolic as well as diastolic dysfunction and rhythm disturbances, in order to keep a steady homeostasis in the human body. Literally, blunted contractile responsiveness to physical or pharmacological stress, impaired diastolic relaxation and electrophysiological changes, primarily QT interval prolongation, do occur progressively in a cirrhotic patient with no known preexisting cardiac disease. This condition is identified as cirrhotic cardiomyopathy (CCM), an entity different from that seen in alcoholic cardiac muscle disease. For the past decades, clinicians did study and attempt to understand the pathophysiology and clinical significance of this process. Indeed, various factors have been identified acting at the molecular and cellular level. Electrocardiography, echocardiography and various serum biomarkers are the main tools that help healthcare practitioners to point to the correct diagnosis. Noteworthy, the subjects that suffer from cirrhotic cardiomyopathy may progress to heart failure during invasive procedures such as surgery, insertion of a transjugular intrahepatic portosystemic shunting (TIPS) and liver transplantation. Besides, several studies have illustrated that CCM is a contributing factor, or even a precipitant, of hepatorenal syndrome (HRS), a conceivable reversible kidney failure in patients with liver cirrhosis and ascites. The treatment is the same as it is in the patients with liver cirrhosis and heart failure and there is no particular treatment for cirrhotic cardiomyopathy. Hence, it is of utmost importance to clearly comprehend the pathophysiology of this disease in order to design more accurate diagnostic tools and definitive treatments in a way to prevent the complications of cirrhosis and overt heart failure. The objective of this review is to describe in a comprehensive way the pathological alterations that occur in the cardiovascular system of cirrhotic patients. It will also point the limitations that remain in the diagnosis and treatment strategies and more importantly, this review will alert the clinicians in the modern era to further observe and record additional pathological changes in this subset of patients.
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Affiliation(s)
- Spyros P Dourakis
- 2nd Department of Internal Medicine and Research Laboratory, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens, Greece
| | - Eleni Geladari
- Internal Medicine Department, Evaggelismos General Hospital, Athens, Greece
| | | | - Natalia Vallianou
- Internal Medicine Department, Evaggelismos General Hospital, Athens, Greece
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The systemic inflammation hypothesis: Towards a new paradigm of acute decompensation and multiorgan failure in cirrhosis. J Hepatol 2021; 74:670-685. [PMID: 33301825 DOI: 10.1016/j.jhep.2020.11.048] [Citation(s) in RCA: 263] [Impact Index Per Article: 65.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 11/24/2020] [Accepted: 11/30/2020] [Indexed: 12/11/2022]
Abstract
Acute decompensation (AD) of cirrhosis is defined by the development of ascites, hepatic encephalopathy and/or variceal bleeding. Ascites is traditionally attributed to splanchnic arterial vasodilation and left ventricular dysfunction, hepatic encephalopathy to hyperammonaemia, and variceal haemorrhage to portal hypertension. Recent large-scale European observational studies have shown that systemic inflammation is a hallmark of AD. Here we present a working hypothesis, the systemic inflammation hypothesis, suggesting that systemic inflammation through an impairment of the functions of one or more of the major organ systems may be a common theme and act synergistically with the traditional mechanisms involved in the development of AD. Systemic inflammation may impair organ system function through mechanisms which are not mutually exclusive. The first mechanism is a nitric oxide-mediated accentuation of the preexisting splanchnic vasodilation, resulting in the overactivation of the endogenous vasoconstrictor systems which elicit intense vasoconstriction and hypoperfusion in certain vascular beds, in particular the renal circulation. Second, systemic inflammation may cause immune-mediated tissue damage, a process called immunopathology. Finally, systemic inflammation may induce important metabolic changes. Indeed, systemic inflammatory responses are energetically expensive processes, requiring reallocation of nutrients (glucose, amino acids and lipids) to fuel immune activation. Systemic inflammation also inhibits nutrient consumption in peripheral (non-immune) organs, an effect that may provide one mechanism of reallocation and prioritisation of metabolic fuels for inflammatory responses. However, the decrease in nutrient consumption in peripheral organs may result in decreased mitochondrial production of ATP (energy) and subsequently impaired organ function.
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Héla E, Sofien K, Kamel L, Asma O, Dalila G, Sondos K, Jamel K. QT interval abnormalities and heart rate variability in patients with cirrhosis. Arab J Gastroenterol 2020; 21:246-252. [PMID: 33012676 DOI: 10.1016/j.ajg.2020.08.001] [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: 02/04/2020] [Revised: 04/10/2020] [Accepted: 08/11/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND AND STUDY AIMS We aimed to assess the relationship of the QT interval and heart rate variability with the severity and aetiology of cirrhosis and determine the effect of propranolol on them. PATIENTS AND METHODS This prospective study included 44 patients with cirrhosis categorised into three groups based on the Child-Pugh score: groups 1, 2 and 3 (with 12, 15 and 15 patients, respectively). Demographic characteristics, propranolol administration, severity of cirrhosis evaluated by the Child-Pugh score, aetiology of cirrhosis, and serum sodium, potassium and calcium levels were evaluated. All patients underwent 24 h-Holter monitoring. Corrected QT interval (QTc), average heart rate, standard deviation of normal-to-normal intervals (SDNN) and corrected SDNN (cSDNN) were evaluated. RESULTS The average QTc was significantly longer in group 3 than in groups 1 and 2 (453.4 ± 17.4 vs 422.8 ± 18.6 and 428.9 ± 17.24 ms, p < 0.001). The median SDNN was 70 ms and was significantly lower in group 3 vs groups 1 and 2 (77; interquartile range [IQR], 67-89.5 vs 57; IQR, 38-68 and 75 ms; IQR, 61-81 ms, p = 0.003). cSDNN was significantly lower in group 3 vs groups 1 and 2 (200.0 ± 42.6 vs 254.5 ± 75.3 and 277.8 ± 110.6 ms, p = 0.022). Propranolol administration resulted in a significant increase in the average SDNN value but had no effect on cSDNN or QTc. QTc was associated with the Child-Pugh class (p < 0.001), viral aetiology (p = 0.009) and sex (p = 0.010); SDNN was associated with the mean heart rate (p = 0.015) and Child-Pugh class (p = 0.024). CONCLUSION QTc interval prolongation and decreased SDNN are common in cirrhosis. Their prevalence is closely associated with disease severity. Propranolol has no effects on cSDNN or QTc.
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Affiliation(s)
- Elloumi Héla
- Department of Gastroenterology, Habib Thameur Hospital, University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
| | - Kamoun Sofien
- Department of Cardiology, Habib Thameur Hospital, University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia.
| | - Ltaief Kamel
- Department of Gastroenterology, Habib Thameur Hospital, University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
| | - Ouakaa Asma
- Department of Gastroenterology, Habib Thameur Hospital, University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
| | - Gargouri Dalila
- Department of Gastroenterology, Habib Thameur Hospital, University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
| | - Kraiem Sondos
- Department of Cardiology, Habib Thameur Hospital, University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
| | - Kharrat Jamel
- Department of Gastroenterology, Habib Thameur Hospital, University of Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
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Trebicka J, Fernandez J, Papp M, Caraceni P, Laleman W, Gambino C, Giovo I, Uschner FE, Jimenez C, Mookerjee R, Gustot T, Albillos A, Bañares R, Janicko M, Steib C, Reiberger T, Acevedo J, Gatti P, Bernal W, Zeuzem S, Zipprich A, Piano S, Berg T, Bruns T, Bendtsen F, Coenraad M, Merli M, Stauber R, Zoller H, Ramos JP, Solè C, Soriano G, de Gottardi A, Gronbaek H, Saliba F, Trautwein C, Özdogan OC, Francque S, Ryder S, Nahon P, Romero-Gomez M, Van Vlierberghe H, Francoz C, Manns M, Garcia E, Tufoni M, Amoros A, Pavesi M, Sanchez C, Curto A, Pitarch C, Putignano A, Moreno E, Shawcross D, Aguilar F, Clària J, Ponzo P, Jansen C, Vitalis Z, Zaccherini G, Balogh B, Vargas V, Montagnese S, Alessandria C, Bernardi M, Ginès P, Jalan R, Moreau R, Angeli P, Arroyo V. The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology. J Hepatol 2020; 73:842-854. [PMID: 32673741 DOI: 10.1016/j.jhep.2020.06.013] [Citation(s) in RCA: 321] [Impact Index Per Article: 64.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Revised: 06/05/2020] [Accepted: 06/06/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF. METHODS A total of 1,071 patients with AD were enrolled. We collected detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed up for 3 months. Outcomes (liver transplantation and death) at 1 year were also recorded. RESULTS Three groups of patients were identified. Pre-ACLF patients (n = 218) developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n = 233) required ≥1 readmission but did not develop ACLF and had mortality rates of 21.0% and 35.6%, respectively. Stable decompensated cirrhosis (SDC) patients (n = 620) were not readmitted, did not develop ACLF and had a 1-year mortality rate of only 9.5%. The 3 groups differed significantly regarding the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in SDC) and the prevalence of surrogates of severe portal hypertension throughout the study (high in UDC vs. low in pre-ACLF and SDC). CONCLUSIONS Acute decompensation without ACLF is a heterogeneous condition with 3 different clinical courses and 2 major pathophysiological mechanisms: systemic inflammation and portal hypertension. Predicting the development of ACLF remains a major future challenge. CLINICALTRIALS. GOV NUMBER NCT03056612. LAY SUMMARY Herein, we describe, for the first time, 3 different clinical courses of acute decompensation (AD) of cirrhosis after hospital admission. The first clinical course includes patients who develop acute-on-chronic liver failure (ACLF) and have a high short-term risk of death - termed pre-ACLF. The second clinical course (unstable decompensated cirrhosis) includes patients requiring frequent hospitalizations unrelated to ACLF and is associated with a lower mortality risk than pre-ACLF. Finally, the third clinical course (stable decompensated cirrhosis), includes two-thirds of all patients admitted to hospital with AD - patients in this group rarely require hospital admission and have a much lower 1-year mortality risk.
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Affiliation(s)
- Jonel Trebicka
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; JW Goethe University Hospital, Frankfurt, Germany.
| | - Javier Fernandez
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; Hospital Clinic, IDIBAPS and CIBEehd, Barcelona, Spain
| | - Maria Papp
- University of Debrecen, Faculty of Medicine, Institute of Medicine, Department of Gastroenterology, Debrecen, Hungary
| | | | | | | | - Ilaria Giovo
- Division of Gastroenterology and Hepatology, Città della Salute e della Scienza Hospital, University of Torino, Torino, Italy
| | | | - Cesar Jimenez
- Liver Unit, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, CIBEREHD, Barcelona, Spain
| | | | | | - Agustin Albillos
- Department of Gastroenterology, Hospital Universitario Ramón y Cajal, IRYCIS, University of Alcalá, CIBEREHD, Madrid, Spain
| | - Rafael Bañares
- Gastroenterology and Hepatology Department, Hospital General Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, CIBERehd, Madrid, Spain
| | - Martin Janicko
- Pavol Jozef Safarik University in Kosice, Kosice, Slovakia
| | - Christian Steib
- Department of Medicine II, University Hospital Munich, Munich, Germany
| | | | - Juan Acevedo
- University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - Pietro Gatti
- Internal Medicine PO Ostuni, ASL Brindisi, Italy
| | | | | | | | | | - Thomas Berg
- Division of Hepatology, Department of Medicine II, Leipzig University, Medical Center, Leipzig, Germany
| | - Tony Bruns
- Jena University Hospital, Jena, Germany; Aachen University Hospital, Aachen, Germany
| | | | | | - Manuela Merli
- Department of Translational and Precision Medicine, Universitá Sapienza Roma, Roma, Italy
| | | | - Heinz Zoller
- Medical University of Innsbruck, Innsbruck, Austria
| | | | - Cristina Solè
- Hospital Clinic, IDIBAPS and CIBEehd, Barcelona, Spain
| | - Germán Soriano
- Hospital de la Santa Creu i Sant Pau and CIBERehd, Barcelona, Spain
| | - Andrea de Gottardi
- University Clinic of Visceral Surgery and Medicine-Inselspital, Bern and Ente Ospedaliero Cantonale, Universita della Svizzera Italiana, Lugano, Switzerland
| | | | - Faouzi Saliba
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Universite Paris Saclay, INSERM Unit 1193, Villejuif, France
| | | | | | | | - Stephen Ryder
- NIHR Biomedical Research Centre at Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, United Kingdom
| | - Pierre Nahon
- AP-HP, Hôpital Jean Verdier, Service d'Hépatologie, Bondy; Université Paris 13, Sorbonne Paris Cité, "Equipe labellisée Ligue Contre le Cancer", Saint-Denis; Inserm, UMR-1162, "Génomique fonctionnelle des tumeurs solides", Paris, France
| | | | | | - Claire Francoz
- APHP, Hôpital Beaujon, Service d'Hépatologie, Clichy, France; Inserm, Université de Paris, Centre de Recherche sur L´Inflammation, Paris, France
| | | | - Elisabet Garcia
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain
| | | | - Alex Amoros
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain
| | - Marco Pavesi
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain
| | - Cristina Sanchez
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain
| | - Anna Curto
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain
| | - Carla Pitarch
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain
| | | | - Esau Moreno
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain
| | | | - Ferran Aguilar
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain
| | - Joan Clària
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; Hospital Clinic, IDIBAPS and CIBEehd, Barcelona, Spain
| | - Paola Ponzo
- Division of Gastroenterology and Hepatology, Città della Salute e della Scienza Hospital, University of Torino, Torino, Italy
| | | | - Zsuzsanna Vitalis
- University of Debrecen, Faculty of Medicine, Institute of Medicine, Department of Gastroenterology, Debrecen, Hungary
| | | | - Boglarka Balogh
- University of Debrecen, Faculty of Medicine, Institute of Medicine, Department of Gastroenterology, Debrecen, Hungary
| | - Victor Vargas
- Liver Unit, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, CIBEREHD, Barcelona, Spain
| | | | - Carlo Alessandria
- Division of Gastroenterology and Hepatology, Città della Salute e della Scienza Hospital, University of Torino, Torino, Italy
| | | | - Pere Ginès
- Hospital Clinic, IDIBAPS and CIBEehd, Barcelona, Spain
| | - Rajiv Jalan
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; UCL Medical School, Royal Free Hospital, London, United Kingdom
| | - Richard Moreau
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; APHP, Hôpital Beaujon, Service d'Hépatologie, Clichy, France; Inserm, Université de Paris, Centre de Recherche sur L´Inflammation, Paris, France
| | - Paolo Angeli
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain; Department of Medicine, University of Padova, Padova, Italy
| | - Vicente Arroyo
- European Foundation for Study of Chronic Liver Failure, EF-Clif, Barcelona, Spain
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Development and Validation of a Model to Predict Acute Kidney Injury in Hospitalized Patients With Cirrhosis. Clin Transl Gastroenterol 2020; 10:e00075. [PMID: 31478958 PMCID: PMC6775340 DOI: 10.14309/ctg.0000000000000075] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVES Acute kidney injury (AKI) is a common complication in hospitalized patients with cirrhosis which contributes to morbidity and mortality. Improved prediction of AKI in this population is needed for prevention and early intervention. We developed a model to identify hospitalized patients at risk for AKI. METHODS Admission data from a prospective cohort of hospitalized patients with cirrhosis without AKI on admission (n = 397) was used for derivation. AKI development in the first week of admission was captured. Independent predictors of AKI on multivariate logistic regression were used to develop the prediction model. External validation was performed on a separate multicenter cohort (n = 308). RESULTS In the derivation cohort, the mean age was 57 years, the Model for End-Stage Liver Disease score was 17, and 59 patients (15%) developed AKI after a median of 4 days. Admission creatinine (OR: 2.38 per 1 mg/dL increase [95% CI: 1.47-3.85]), international normalized ratio (OR: 1.92 per 1 unit increase [95% CI: 1.92-3.10]), and white blood cell count (OR: 1.09 per 1 × 10/L increase [95% CI: 1.04-1.15]) were independently associated with AKI. These variables were used to develop a prediction model (area underneath the receiver operator curve: 0.77 [95% CI: 0.70-0.83]). In the validation cohort (mean age of 53 years, Model for End-Stage Liver Disease score of 16, and AKI development of 13%), the area underneath the receiver operator curve for the model was 0.70 (95% CI: 0.61-0.78). DISCUSSION A model consisting of admission creatinine, international normalized ratio, and white blood cell count can identify patients with cirrhosis at risk for in-hospital AKI development. On further validation, our model can be used to apply novel interventions to reduce the incidence of AKI among patients with cirrhosis who are hospitalized.
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Abstract
PURPOSE OF REVIEW Cirrhotic cardiomyopathy is a syndrome of depressed cardiac function in patients with cirrhosis. We aimed to review the historical background, pathophysiology and pathogenesis, diagnostic definitions, clinical relevance, and management of this syndrome. RECENT FINDINGS An inflammatory phenotype underlies the pathogenesis: gut bacterial translocation with endotoxemia stimulates cytokines and cardiodepressant factors, such as nitric oxide and endocannabinoids. Cardiomyocyte plasma membrane biochemical and biophysical changes also play a pathogenic role. These factors lead to impaired beta-adrenergic function. Proposed new echocardiographic criteria for the diagnosis of cirrhotic cardiomyopathy include systolic global longitudinal strain and indices of diastolic dysfunction. Cardiac dysfunction participates in the pathogenesis of hepatorenal syndrome and increased morbidity/mortality of cirrhotic patients to hemorrhage, infection, and surgery, including liver transplantation. There is no specific treatment, although β-adrenergic blockade and supportive management have been proposed, but it needs further study. Cirrhotic cardiomyopathy is a clinically relevant syndrome afflicting patients with established cirrhosis. Optimum management remains unclear, and further study is needed in this area.
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Affiliation(s)
- Ki Tae Yoon
- Liver Unit, University Calgary Cumming School of Medicine, 3330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada.,Liver Center, Department of Internal Medicine, Pusan National University Yangsan Hospital, 20 Geumo-ro, Mulgeum-eup, Yangsan, Gyeongnam, 50612, South Korea
| | - Hongqun Liu
- Liver Unit, University Calgary Cumming School of Medicine, 3330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada
| | - Samuel S Lee
- Liver Unit, University Calgary Cumming School of Medicine, 3330 Hospital Dr NW, Calgary, AB, T2N 4N1, Canada.
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Israelsen M, Dahl EK, Madsen BS, Wiese S, Bendtsen F, Møller S, Fialla AD, Jensen BL, Krag A. Dobutamine reverses the cardio-suppressive effects of terlipressin without improving renal function in cirrhosis and ascites: a randomized controlled trial. Am J Physiol Gastrointest Liver Physiol 2020; 318:G313-G321. [PMID: 31841026 DOI: 10.1152/ajpgi.00328.2019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Acute kidney injury and hepatorenal syndrome (HRS) are frequent complications in patients with cirrhosis and ascites. First-line treatment is terlipressin, which reverses HRS in ~40% of patients but also lowers cardiac output (CO). We aimed to investigate whether reversing the cardio-suppressive effect of terlipressin with the β-adrenoceptor agonist dobutamine would increase CO and thereby increase the glomerular filtration rate (GFR). We randomized 25 patients with cirrhosis, ascites, and impaired renal function (2:2:1): group A received terlipressin followed by the addition of dobutamine; group B received dobutamine and terlipressin as monotherapies; and group C received placebo. Renal and cardiac functions were assessed during 8 clearance periods of 30 min, and concentrations of vasoactive hormones were measured. Dobutamine as a monotherapy increased CO (1.03 L/min, P < 0.01) but had no significant effects on GFR. Renin (P < 0.05), angiotensin II (P < 0.005), and aldosterone (P < 0.05) increased after dobutamine infusion. Terlipressin as a monotherapy improved GFR (18.9 mL·min-1·m-2, P = 0.005) and mean arterial pressure (MAP) (14 mmHg, P = 0.001) but reduced CO (-0.92 L/min, P < 0.005) and renin (P < .005). A combined treatment of dobutamine and terlipressin had a positive effect on CO (1.19 L/min, P < 0.05) and increased renin (P < 0.005), angiotensin II (P < 0.005), and aldosterone (P < 0.05), but it had no significant effects on MAP or GFR. Dobutamine reversed the cardio-suppressive effect of terlipressin in cirrhosis, ascites, and impaired renal function. However, dobutamine reduced peripheral vascular resistance, activated renin-angiotensin-aldosterone system, and did not improve GFR compared with terlipressin as a monotherapy. Therefore, dobutamine cannot be recommended in cirrhosis and ascites.NEW & NOTEWORTHY This study shows that the cardio-suppressive effects of the vasopressin receptor agonist terlipressin can be reversed by dobutamine. This is a novel observation in patients with decompensated cirrhosis. Furthermore, we show that dobutamine reduced the peripheral vascular resistance and activated the renin-angiotensin system, whereas renal function was not further improved by terlipressin alone.
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Affiliation(s)
- Mads Israelsen
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.,Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Emilie Kristine Dahl
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Bjørn Stæhr Madsen
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.,Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Signe Wiese
- Gastro Unit, Copenhagen University Hospital Hvidovre, Denmark.,Center for Functional and Diagnostic Imaging and Research, Department of Clinical Physiology and Nuclear Medicine 260, Faculty of Health Sciences Hvidovre Hospital, University of Copenhagen, Denmark
| | | | - Søren Møller
- Center for Functional and Diagnostic Imaging and Research, Department of Clinical Physiology and Nuclear Medicine 260, Faculty of Health Sciences Hvidovre Hospital, University of Copenhagen, Denmark
| | - Annette Dam Fialla
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| | - Boye L Jensen
- Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - Aleksander Krag
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.,Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Ngwa T, Orman E, Gomez EV, Vuppalanchi R, Kubal C, Chalasani N, Ghabril M. Non-selective beta blocker use is associated with improved short-term survival in patients with cirrhosis referred for liver transplantation. BMC Gastroenterol 2020; 20:4. [PMID: 31906860 PMCID: PMC6945622 DOI: 10.1186/s12876-019-1155-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 12/23/2019] [Indexed: 02/06/2023] Open
Abstract
Background Recent evidence cautions against the use of non-selective beta-blockers (NSBB) in patients with refractory ascites or spontaneous bacterial peritonitis while other data suggests a survival benefit in patients with advanced liver disease. The aim of this study was to describe the use and impact of NSBB in patients with cirrhosis referred for liver transplantation. Methods A single-center cohort of patients with cirrhosis, who were referred and evaluated for liver transplantation between January and June 2012 were studied for baseline characteristics and clinical outcomes. Patients were grouped according to the use of NSBB at initial evaluation, with the endpoint of 90-day mortality. Results Sixty-five (38%) of 170 consecutive patients evaluated for liver transplantation were taking NSBB. Patients taking NSBB had higher MELD and Child Pugh score. NSBB use was associated with lower 90-day mortality (6% vs. 15%) with a risk adjusted hazard ratio of 0.27 (95%CI .09–0.88, p = .03). Patients taking NSBB developed acute kidney injury (AKI) within 90 days more frequently than patients not taking NSBB (22% vs 11%), p = 0.048). However, this was related to increased stage 1 AKI episodes, all of which resolved. Twelve (27%) of 45 patients with > 90 day follow up discontinued NSBB, most commonly for hypotension and AKI, had increased subsequent MELD and mortality. Conclusions NSBB use in patients with cirrhosis undergoing liver transplant evaluation is associated with better short-term survival. Nevertheless, ongoing tolerance of NSBB in this population is dynamic and may select a subset of patients with better hemodynamic reserve.
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Affiliation(s)
- Taiwo Ngwa
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Eric Orman
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Eduardo Vilar Gomez
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Raj Vuppalanchi
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Chandrashekhar Kubal
- Transplant Surgery, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Marwan Ghabril
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA.
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