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Pohl J, Aretakis D, Tacke F, Engelmann C, Sigal M. Role of Intestinal Barrier Disruption to Acute-on-Chronic Liver Failure. Semin Liver Dis 2025. [PMID: 40081417 DOI: 10.1055/a-2516-2361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/16/2025]
Abstract
Acute-on-chronic liver failure (ACLF) is a severe condition in patients with decompensated liver cirrhosis, marked by high short-term mortality. Recent experimental and clinical evidence has linked intestinal dysfunction to both the initiation of ACLF as well as disease outcome. This review discusses the significant role of the gut-liver axis in ACLF pathogenesis, highlighting recent advances. Gut mucosal barrier disruption, gut dysbiosis, and bacterial translocation emerge as key factors contributing to systemic inflammation in ACLF. Different approaches of therapeutically targeting the gut-liver axis via farnesoid X receptor agonists, nonselective beta receptor blockers, antibiotics, and probiotics are discussed as potential strategies mitigating ACLF progression. The importance of understanding the distinct pathophysiology of ACLF compared with other stages of liver cirrhosis is highlighted. In conclusion, research findings suggest that disruption of intestinal integrity may be an integral component of ACLF pathogenesis, paving the way for novel diagnostic and therapeutic approaches to manage this syndrome more effectively.
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Affiliation(s)
- Julian Pohl
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Dimitrios Aretakis
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Cornelius Engelmann
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
- Institute for Liver and Digestive Health, University College London, London, United Kingdom
| | - Michael Sigal
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany
- Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
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Ballester MP, Elshabrawi A, Jalan R. Extracorporeal liver support and liver transplantation for acute-on-chronic liver failure. Liver Int 2025; 45:e15647. [PMID: 37312660 PMCID: PMC11815617 DOI: 10.1111/liv.15647] [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: 04/24/2023] [Revised: 05/31/2023] [Accepted: 06/04/2023] [Indexed: 06/15/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is defined by acute decompensation, organ failure and a high risk of short-term mortality. This condition is characterized by an overwhelming systemic inflammatory response. Despite treating the precipitating event, intensive monitoring and organ support, clinical deterioration can occur with very poor outcomes. During the last decades, several extracorporeal liver support systems have been developed to try to reduce ongoing liver injury and provide an improved environment for the liver to regenerate or as a bridging therapy until liver transplantation. Several clinical trials have been performed to evaluate the clinical efficacy of extracorporeal liver support systems, but no clear impact on survival has been proven. DIALIVE is a novel extracorporeal liver support device that has been built to specifically address the pathophysiological derangements responsible for the development of ACLF by replacing dysfunctional albumin and removing pathogen and damage-associated molecular patterns (PAMPs and DAMPs). In phase II clinical trial, DIALIVE appears to be safe, and it seems to be associated with a faster time to the resolution of ACLF compared with standard medical treatment. Even in patients with severe ACLF, liver transplantation saves lives and there is clear evidence of transplant benefit. Careful selection of patients is required to attain good results from liver transplantation, but many questions remain unanswered. In this review, we describe the current perspectives on the use of extracorporeal liver support and liver transplantation for ACLF patients.
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Affiliation(s)
- Maria Pilar Ballester
- Digestive Disease DepartmentHospital Clínico Universitario de ValenciaValenciaSpain
- INCLIVA Biomedical Research InstituteHospital Clínico Universitario de ValenciaValenciaSpain
| | - Ahmed Elshabrawi
- Liver Failure Group, Institute for Liver & Digestive HealthUniversity College LondonLondonUK
- Endemic Hepatology and Gastroenterology DepartmentMansoura UniversityMansouraEgypt
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver & Digestive HealthUniversity College LondonLondonUK
- European Foundation for the Study of Chronic Liver Failure (EF Clif)BarcelonaSpain
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3
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Han Z, Qi L, Chen S, Zhang J, Guo X, Liang C, Zheng W. Predictive value of neutrophil-to-lymphocyte ratio and MELD score for short-term survival of patients with HBV-DeCi. Biomark Med 2025; 19:43-49. [PMID: 39781609 PMCID: PMC11749384 DOI: 10.1080/17520363.2024.2448112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 12/26/2024] [Indexed: 01/12/2025] Open
Abstract
OBJECTIVE The prognostic value of neutrophil-to-lymphocyte ratio (NLR) combined with Model for End-Stage Liver Disease (MELD) score was evaluated for hepatitis B virus-associated decompensated cirrhosis (HBV-DeCi). METHODS The 30-day mortality of 166 hBV-DeCi patients was examined. Receiver operating characteristic curve analysis and multivariate regression analysis were used to assess the performance of NLR for prediction of poor outcomes. RESULTS The 30-day mortality rate was 10.2% (17/166). NLR was significantly lower in survivors than in non-survivors, and could be used for prognosis prediction in HBV-DeCi patients. Area under the curve was higher for NLR combined with MELD score than for each factor alone. (MELD score, AUC:0.864、NLR, AUC:0.781, Combined, AUC:0.920) The Odds ratio of MELD score is lower than NLR.(MELD score:1.447&NLR:1.745). CONCLUSIONS The findings demonstrate that NLR combined with MELD score has a high prognostic value for HBV-DeCi patients.
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Affiliation(s)
- Zhong Han
- Department of Laboratory Medicine, Shengzhou People’s Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University School of Medicine, the Shengzhou Hospital of Shaoxing University, Shengzhou, Zhejiang, China
| | - Liangshuai Qi
- School of Laboratory Medicine, Bengbu Medical University, Bengbu, Anhui, China
| | - Sirui Chen
- School of Laboratory Medicine, Bengbu Medical University, Bengbu, Anhui, China
| | - Jinfei Zhang
- Department of Laboratory Medicine, Shengzhou People’s Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University School of Medicine, the Shengzhou Hospital of Shaoxing University, Shengzhou, Zhejiang, China
| | - Xueliang Guo
- Department of Internal Medicine, Shengzhou People’s Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University School of Medicine, the Shengzhou Hospital of Shaoxing University, Shengzhou, Zhejiang, China
| | - Chunying Liang
- Department of Pharmacy, XinChang Hospital of Chinese Medicine, XinChang, Zhejiang, China
| | - Weiwei Zheng
- Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
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4
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Brozat JF, Pohl J, Engelmann C, Tacke F. [Liver transplantation in acute and acute-on-chronic liver failure]. Med Klin Intensivmed Notfmed 2024; 119:484-492. [PMID: 39043956 DOI: 10.1007/s00063-024-01158-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 06/04/2024] [Indexed: 07/25/2024]
Abstract
Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are diseases with a rapidly progressive course and high mortality. Apart from treating the underlying triggers and intensive care measures, there are very limited therapeutic options for either condition. Liver transplantation is often the only life-saving treatment, but it cannot always be employed due to contraindications and severe disease progression. ACLF is characterized by underlying liver cirrhosis and typical triggers such as bacterial infections, bleeding, or alcohol binges. ALF occurs in previously healthy livers, usually as a result of purely hepatotoxic events. Disease differences are also reflected in the course and regulations of liver transplantation. Newer prognostic parameters and prioritization programs for ACLF can help improve both waiting list mortality and outcomes after transplantation.
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Affiliation(s)
- Jonathan F Brozat
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Charité Mitte (CCM) und Campus Virchow-Klinikum (CVK), Augustenburger Platz 1, 15335, Berlin, Deutschland
| | - Julian Pohl
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Charité Mitte (CCM) und Campus Virchow-Klinikum (CVK), Augustenburger Platz 1, 15335, Berlin, Deutschland
| | - Cornelius Engelmann
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Charité Mitte (CCM) und Campus Virchow-Klinikum (CVK), Augustenburger Platz 1, 15335, Berlin, Deutschland
| | - Frank Tacke
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Charité Mitte (CCM) und Campus Virchow-Klinikum (CVK), Augustenburger Platz 1, 15335, Berlin, Deutschland.
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5
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Maiwall R, Singh SP, Angeli P, Moreau R, Krag A, Singh V, Singal AK, Tan SS, Puri P, Mahtab M, Lau G, Ning Q, Sharma MK, Rao PN, Kapoor D, Gupta S, Duseja A, Wadhawan M, Jothimani D, Saigal S, Taneja S, Shukla A, Puri P, Govil D, Pandey G, Madan K, Eapen CE, Benjamin J, Chowdhury A, Singh S, Salao V, Yang JM, Hamid S, Shalimar, Jasuja S, Kulkarni AV, Niriella MA, Tevethia HV, Arora V, Mathur RP, Roy A, Jindal A, Saraf N, Verma N, De A, Choudhary NS, Mehtani R, Chand P, Rudra O, Sarin SK. APASL clinical practice guidelines on the management of acute kidney injury in acute-on-chronic liver failure. Hepatol Int 2024; 18:833-869. [PMID: 38578541 DOI: 10.1007/s12072-024-10650-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 01/20/2024] [Indexed: 04/06/2024]
Abstract
Acute-on-chronic liver failure (ACLF) is a syndrome that is characterized by the rapid development of organ failures predisposing these patients to a high risk of short-term early death. The main causes of organ failure in these patients are bacterial infections and systemic inflammation, both of which can be severe. For the majority of these patients, a prompt liver transplant is still the only effective course of treatment. Kidneys are one of the most frequent extrahepatic organs that are affected in patients with ACLF, since acute kidney injury (AKI) is reported in 22.8-34% of patients with ACLF. Approach and management of kidney injury could improve overall outcomes in these patients. Importantly, patients with ACLF more frequently have stage 3 AKI with a low rate of response to the current treatment modalities. The objective of the present position paper is to critically review and analyze the published data on AKI in ACLF, evolve a consensus, and provide recommendations for early diagnosis, pathophysiology, prevention, and management of AKI in patients with ACLF. In the absence of direct evidence, we propose expert opinions for guidance in managing AKI in this very challenging group of patients and focus on areas of future research. This consensus will be of major importance to all hepatologists, liver transplant surgeons, and intensivists across the globe.
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - Satender Pal Singh
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - Paolo Angeli
- Department of Internal Medicine and Hepatology, University of Padova, Padua, Italy
| | - Richard Moreau
- European Foundation for the Study of Chronic Liver Failure (EF CLIF), European Association for the Study of the Liver (EASL)-CLIF Consortium, and Grifols Chair, Barcelona, Spain
- Centre de Recherche sur l'Inflammation (CRI), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Cité, Paris, France
- Service d'Hépatologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Beaujon, Clichy, France
| | - Aleksander Krag
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
| | - Virender Singh
- Punjab Institute of Liver and Biliary Sciences, Mohali, Punjab, India
| | - Ashwani K Singal
- Department of Medicine, University of Louisville School of Medicine, Trager Transplant Center and Jewish Hospital, Louisville, USA
| | - S S Tan
- Department of Medicine, Hospital Selayang, Bata Caves, Selangor, Malaysia
| | - Puneet Puri
- Department of Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Mamun Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - George Lau
- Humanity and Health Medical Group, Humanity and Health Clinical Trial Center, Hong Kong SAR, China
- The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, 100039, China
| | - Qin Ning
- Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- State Key Laboratory for Zoonotic Diseases, Wuhan, China
- Department of Pediatrics, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Manoj Kumar Sharma
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - P N Rao
- Department of Hepatology and Nutrition, Asian Institute of Gastroenterology, Hyderabad, India
| | - Dharmesh Kapoor
- Department of Hepatology, Gleneagles Global Hospitals, Hyderabad, Telangana, India
| | - Subhash Gupta
- Department of Surgery, Center for Liver and Biliary Sciences, Max Healthcare, Saket, New Delhi, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Manav Wadhawan
- Institute of Digestive & Liver Diseases, BLK Superspeciality Hospital Delhi, New Delhi, India
| | - Dinesh Jothimani
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharat Institute of Higher Education and Research, Chennai, India
| | - Sanjiv Saigal
- Department of Gastroenterology and Hepatology, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, Saket, New Delhi, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Akash Shukla
- Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai, India
| | - Pankaj Puri
- Fortis Escorts Liver & Digestive Diseases Institute, New Delhi, India
| | - Deepak Govil
- Department of Critical Care and Anaesthesia, Medanta-The Medicity, Gurugram, Haryana, India
| | - Gaurav Pandey
- Gastroenterology and Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Kaushal Madan
- Department of Gastroenterology and Hepatology, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, Saket, New Delhi, India
| | - C E Eapen
- Department of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Jaya Benjamin
- Department of Clinical Nutrition, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ashok Chowdhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - Shweta Singh
- Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, Saket, New Delhi, India
| | - Vaishali Salao
- Department of Critical Care, Fortis Hospital, Mulund, Mumbai, India
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Saeed Hamid
- Department of Hepatology, Aga Khan University, Karachi, Pakistan
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Sanjiv Jasuja
- Department of Nephrology, Indraprastha Apollo Hospitals, New Delhi, India
| | | | - Madund A Niriella
- Department of Medicine, Faculty of Medicine, University of Kelaniya, Colombo, Sri Lanka
| | - Harsh Vardhan Tevethia
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - Vinod Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - R P Mathur
- Department of Nephrology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Akash Roy
- Department of Gastroenterology, Institute of Gastrosciences and Liver Transplantation, Apollo Hospitals, Kolkata, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - Neeraj Saraf
- Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurgaon, Delhi (NCR), India
| | - Nipun Verma
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Arka De
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Narendra S Choudhary
- Department of Hepatology and Liver Transplantation, Medanta-The Medicity Hospital, Gurugram, Haryana, India
| | - Rohit Mehtani
- Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai, India
| | - Phool Chand
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - Omkar Rudra
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India.
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Belfiore J, Castellani Niccolini N, Fleissner Z, Chadha R, Biancofiore G. Pain management in liver transplant recipients: a focus on current and future strategies. Minerva Anestesiol 2024; 90:452-461. [PMID: 38571405 DOI: 10.23736/s0375-9393.24.17805-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/05/2024]
Abstract
Liver transplantation is the only curative treatment option for patients with end-stage liver disease. Anesthesiologists and intensivists are fully involved in this procedure due to the perioperative care focus on hemodynamic, respiratory and metabolic support. However, quite surprisingly, postoperative pain management does not have clinical primary consideration in this class of patients due to a combination of factors including the thought that liver transplantation recipients have less pain and require lower doses of analgesics than patients who undergo other types of major abdominal surgery. Other factors contribute to make the management of postoperative pain somewhat complex in this class of patients: 1) drug pharmacokinetics and metabolism by the new liver is not predictable; 2) the multifactorial nature of liver graft recovery; and 3) the alterations of homeostasis, including circulatory, respiratory and metabolic vulnerability, in the days postoperative period. As a result, post-liver transplantation analgesia is underestimated not only from the clinical point of view but also in the literature and only a few papers deal with the management of postoperative pain in this particular class of patients. Thus, in the experts' opinion paper we aimed to report the possible strategies for managing post-LT pain with a focus on opioids alternatives and possible future developments in this particular clinical setting also in the view that improvements in perioperative care have made it possible to adopt fast track and Enhanced Recovery After Surgery-oriented protocols also in this class of patients.
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Affiliation(s)
- Jacopo Belfiore
- Unit of Transplant Anesthesia and Critical Care, AOU Pisana, University of Pisa, Pisa, Italy
| | | | - Zachary Fleissner
- Unit of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, FL, USA
| | - Ryan Chadha
- Unit of Anesthesiology and Perioperative Medicine, Mayo Clinic, Jacksonville, FL, USA
| | - Gianni Biancofiore
- Unit of Transplant Anesthesia and Critical Care, AOU Pisana, University of Pisa, Pisa, Italy -
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7
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Zhou H, Liu Y, Su Y, Ji P, Kong L, Sun R, Zhang D, Xu H, Li W, Li W. Ginsenoside Rg1 attenuates lipopolysaccharide-induced chronic liver damage by activating Nrf2 signaling and inhibiting inflammasomes in hepatic cells. JOURNAL OF ETHNOPHARMACOLOGY 2024; 324:117794. [PMID: 38244950 DOI: 10.1016/j.jep.2024.117794] [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: 10/04/2023] [Revised: 01/09/2024] [Accepted: 01/18/2024] [Indexed: 01/22/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Ginseng (Panax ginseng C. A. Meyer) is a precious traditional Chinese medicine with multiple pharmacological effects. Ginsenoside Rg1 is a main active ingredient extracted from ginseng, which is known for its age-delaying and antioxidant effects. Increasing evidence indicates that Rg1 exhibits anti-inflammatory properties in numerous diseases and may ameliorate oxidative damage and inflammation in many chronic liver diseases. AIM OF THE STUDY Chronic inflammatory injury in liver cells is an important pathological basis of many liver diseases. However, its mechanism remains unclear and therapeutic strategies to prevent its development need to be further explored. Thus, our study is to delve the protective effect and mechanism of Rg1 against chronic hepatic inflammatory injuries induced by lipopolysaccharide (LPS). MATERIALS AND METHODS The chronic liver damage model in mice was build up by injecting intraperitoneally with LPS (200 μg/kg) for 21 days. Serum liver function indicators and levels of IL-1β, IL-6 and TNF-α were examined by using corresponding Kits. Hematoxylin and Eosin (H&E), Periodic acid-Schiff (PAS), and Masson stains were utilized to visualize hepatic histopathological damage, glycogen deposition, and liver fibrosis. The nuclear import of p-Nrf2 and the generation of Col4 in the liver were detected by IF, while IHC was employed to detect the expressions of NLRP3 and AIM2 in the hepatic. The Western blot and q-PCR were used to survey the expressions of proteins and mRNAs of fibrosis and apoptosis, and the expressions of Keap1, p-Nrf2 and NLRP3, NLRP1, AIM2 inflammasome-related proteins in mouse liver. The cell viability of human hepatocellular carcinoma cells (HepG2) was detected by Cell Counting Kit-8 to select the action concentration of LPS, and intracellular ROS generation was detected using a kit. The expressions of Nuclear Nrf2, HO-1, NQO1 and NLRP3, NLRP1, and AIM2 inflammasome-related proteins in HepG2 cells were detected by Western blot. Finally, the feasibility of the molecular interlinking between Rg1 and Nrf2 was demonstrated by molecular docking. RESULTS Rg1 treatment for 21 days decreased the levels of ALT, AST, and inflammatory factors of serum IL-1β, IL-6 and TNF-α in mice induced by LPS. Pathological results indicated that Rg1 treatment obviously alleviated hepatocellular injury and apoptosis, inflammatory cell infiltration and liver fibrosis in LPS stimulated mice. Rg1 promoted Keap1 degradation and enhanced the expressions of p-Nrf2, HO-1 and decreased the levels of NLRP1, NLRP3, AIM2, cleaved caspase-1, IL-1β and IL-6 in livers caused by LPS. Furthermore, Rg1 effectively suppressed the rise of ROS in HepG2 cells induced by LPS, whereas inhibition of Nrf2 reversed the role of Rg1 in reducing the production of ROS and NLRP3, NLRP1, and AIM2 expressions in LPS-stimulated HepG2 cells. Finally, the molecular docking illustrated that Rg1 exhibits a strong affinity towards Nrf2. CONCLUSION The findings indicate that Rg1 significantly ameliorates chronic liver damage and fibrosis induced by LPS. The mechanism may be mediated through promoting the dissociation of Nrf2 from Keap1 and then activating Nrf2 signaling and further inhibiting NLRP3, NLRP1, and AIM2 inflammasomes in liver cells.
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Affiliation(s)
- Huimin Zhou
- Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, 230032, China
| | - Yan Liu
- Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, 230032, China
| | - Yong Su
- Department of Pharmacy, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, China
| | - Pengmin Ji
- Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, 230032, China
| | - Liangliang Kong
- Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, 230032, China
| | - Ran Sun
- Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, 230032, China
| | - Duoduo Zhang
- Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, 230032, China
| | - Hanyang Xu
- Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, 230032, China
| | - Weiping Li
- Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, 230032, China.
| | - Weizu Li
- Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, 230032, China.
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8
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Mao W, Yuan M, He X, Zhang Q. Red cell distribution width-to-albumin ratio is a predictor of survival in hepatitis B virus-associated decompensated cirrhosis. Lab Med 2024; 55:127-131. [PMID: 37289932 DOI: 10.1093/labmed/lmad048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2023] Open
Abstract
OBJECTIVE The aim of this study was to ascertain whether red cell distribution width-to-albumin ratio (RAR) is associated with survival in hepatitis B virus (HBV)-associated decompensated cirrhosis (DC) patients. METHODS A cohort of 167 patients with confirmed HBV-DC was enrolled in our study. Demographic characteristics and laboratory data were obtained. The main endpoint was mortality at 30 days. The receiver operating characteristic curve and multivariable regression analysis were used to assess the power of RAR for predicting prognosis. RESULTS Mortality at 30 days was 11.4% (19/167). The RAR levels were higher in the nonsurvivors than the survivors, and elevated RAR levels were clearly associated with poor prognosis. Moreover, the predictive powers of RAR and Model for End-Stage Liver Disease score were not obviously different. CONCLUSION Our data indicate that RAR is a novel potential prognostic biomarker of mortality in HBV-DC.
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Affiliation(s)
- WeiLin Mao
- Department of Clinical Laboratory, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - ManChun Yuan
- Department of Clinical Laboratory, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Xia He
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
| | - Qiu Zhang
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
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9
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Germani G, Ferrarese A, D'Arcangelo F, Russo FP, Senzolo M, Gambato M, Zanetto A, Cillo U, Feltracco P, Persona P, Serra E, Feltrin G, Carretta G, Capizzi A, Donato D, Tessarin M, Burra P. The role of an integrated referral program for patients with liver disease: A network between hub and spoke centers. United European Gastroenterol J 2024; 12:76-88. [PMID: 38087960 PMCID: PMC10859718 DOI: 10.1002/ueg2.12475] [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: 03/20/2023] [Accepted: 07/31/2023] [Indexed: 02/13/2024] Open
Abstract
INTRODUCTION Access to Liver transplantation (LT) can be affected by several barriers, resulting in delayed referral and increased risk of mortality due to complications of the underlying liver disease. AIM To assess the clinical characteristics and outcomes of patients with acute or chronic liver disease referred using an integrated referral program. MATERIALS AND METHODS An integrated referral program was developed in 1 October 2017 based on email addresses and a 24/7 telephone availability. All consecutive adult patients with liver disease referred for the first time using this referral program were prospectively collected until 1 October 2021. Characteristics and outcomes of inpatients were compared with a historical cohort of patients referred without using the integrated referral program (1 October 2015-1 October 2017). Patients were further divided according to pre- and post-Covid-19 pandemic. RESULTS Two hundred eighty-one referred patients were considered. End stage liver disease was the most common underlying condition (79.3%), 50.5% of patients were referred as inpatients and 74.7% were referred for LT evaluation. When inpatient referrals (n = 142) were compared with the historical cohort (n = 86), a significant increase in acute liver injury due to drugs/herbals and supplements was seen (p = 0.01) as well as an increase in End stage liver disease due to alcohol-related liver disease and NASH, although not statistically significant. A significant increase in referrals for evaluation for Trans-jugular intrahepatic portosystemic shunt placement was seen over time (5.6% vs. 1%; p = 0.01) as well as for LT evaluation (84.5% vs. 81%; p = 0.01). Transplant-free survival was similar between the study and control groups (p = 0.3). The Covid-19 pandemic did not affect trends of referrals and patient survival. CONCLUSIONS The development of an integrated referral program for patients with liver disease can represent the first step to standardize already existing referral networks between hub and spoke centers. Future studies should focus on the timing of referral according to different etiologies to optimize treatment options and outcomes.
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Affiliation(s)
- Giacomo Germani
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Alberto Ferrarese
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Francesca D'Arcangelo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Marco Senzolo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Alberto Zanetto
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Paolo Feltracco
- Intensive Care Unit, Padua University Hospital, Padua, Italy
| | - Paolo Persona
- Intensive Care Unit, Padua University Hospital, Padua, Italy
| | - Eugenio Serra
- Intensive Care Unit, Padua University Hospital, Padua, Italy
| | | | | | - Alfio Capizzi
- Medical Direction, Padua University Hospital, Padua, Italy
| | - Daniele Donato
- Medical Direction, Padua University Hospital, Padua, Italy
| | | | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
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10
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Goyes D, Trivedi HD, Curry MP. Prognostic Models in Acute-on-Chronic Liver Failure. Clin Liver Dis 2023; 27:681-690. [PMID: 37380291 DOI: 10.1016/j.cld.2023.03.011] [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: 06/30/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by severe hepatic dysfunction leading to multiorgan failure in patients with end-stage liver disease. ACLF is a challenging clinical syndrome with a rapid clinical course and high short-term mortality. There is no single uniform definition of ACLF or consensus in predicting ACLF-related outcomes, which makes comparing studies difficult and standardizing management protocols challenging. This review aims to provide insights into the common prognostic models that define and grade ACLF.
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Affiliation(s)
- Daniela Goyes
- Department of Medicine, Loyola Medicine - MacNeal Hospital, Berwyn, IL, USA
| | - Hirsh D Trivedi
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Michael P Curry
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
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11
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Zhang Q, Mao W, He X, Yuan M. High red cell distribution width-to-platelet ratio indicates adverse outcomes for hepatitis B virus-associated decompensated cirrhosis. Biomark Med 2023; 17:189-196. [PMID: 37158064 DOI: 10.2217/bmm-2023-0123] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/10/2023] Open
Abstract
Background: This work was designed to determine the association between red cell distribution width-to-platelet ratio (RPR) and 30-day prognosis in hepatitis B virus-associated decompensated cirrhosis (HBV-DC) patients. Methods: A total of 168 HBV-DC patients were included. Independent risk factors for poor prognosis were determined by logistic regression analyses. Results: A total of 21 (12.5%) patients died within 30 days. RPR was higher in nonsurvivors than in survivors. Multivariate analysis identified RPR and Model for End-Stage Liver Disease (MELD) score as independent prognostic predictors, and the predictive value of RPR was similar to that of the MELD score. Moreover, combining RPR with the MELD score further improved the predictive value for mortality. Conclusion: RPR has potential as a reliable tool for the prediction of poor prognosis in HBV-DC patients.
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Affiliation(s)
- Qiu Zhang
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, 312400, China
| | - WeiLin Mao
- Department of Clinical Laboratory, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China
| | - Xia He
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, 312400, China
| | - ManChun Yuan
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, 312400, China
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12
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Choi MC, Min EK, Yim SH, Lee JG, Koo BN, Kim H, Lee HW, Joo DJ, Kim MS. Successful recovery after veno-arterio-venous extracorporeal membrane oxygenation immediately before liver transplantation in multi-organ failure including acute respiratory distress syndrome: A Case Report. Transplant Proc 2023; 55:684-686. [PMID: 36914436 PMCID: PMC9951045 DOI: 10.1016/j.transproceed.2023.02.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 02/18/2023] [Indexed: 03/14/2023]
Abstract
Extracorporeal membrane oxygenation (ECMO) has emerged as an alternative treatment to conventional ventilation maneuvers in the nontransplantation literature to support acute respiratory distress syndrome. However, the role of ECMO in transplant is unclear, and few case reports have described using ECMO pretransplant. We discuss the successful use of veno-arteriovenous ECMO as a bridge therapy to deceased donor liver transplant (LT) in acute respiratory distress syndrome. Because the incidence of severe pulmonary complications resulting in acute respiratory distress syndrome with multiorgan failure is rare before LT, determining the usefulness of ECMO is challenging. However, in acute but reversible respiratory failure and cardiovascular failure, veno-arteriovenous ECMO provides a useful therapeutic option as a bridge for patients awaiting LT and should be considered if available even in multiorgan failure.
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Affiliation(s)
- Mun Chae Choi
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Eun-Ki Min
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Seung Hyuk Yim
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea.
| | - Bon-Nyeo Koo
- Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, South Korea
| | - Hyohyun Kim
- Division of Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, South Korea
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13
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Yao J, Lei YG, Yi HM, Yang Y. Clinical strategies to improve the survival rate of liver recipients with acute-on-chronic liver failure. Hepatobiliary Pancreat Dis Int 2023; 22:41-44. [PMID: 36464623 DOI: 10.1016/j.hbpd.2022.11.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 11/13/2022] [Indexed: 11/23/2022]
Affiliation(s)
- Jia Yao
- Department of Hepatic Surgery, Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Guangdong Key Laboratory of Liver Disease Research, Guangzhou 510630, China
| | - Yun-Guo Lei
- Department of Hepatic Surgery, Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Guangdong Key Laboratory of Liver Disease Research, Guangzhou 510630, China
| | - Hui-Min Yi
- Surgical Intensive Care Unit, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
| | - Yang Yang
- Department of Hepatic Surgery, Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Guangdong Key Laboratory of Liver Disease Research, Guangzhou 510630, China.
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14
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Watanabe Y, Abe H, Kimura N, Arao Y, Ishikawa N, Yuichiro M, Setsu T, Sakamaki A, Kamimura H, Yokoo T, Kamimura K, Tsuchiya A, Terai S. Navitoclax improves acute-on-chronic liver failure by eliminating senescent cells in mice. Hepatol Res 2023; 53:460-472. [PMID: 36628578 DOI: 10.1111/hepr.13879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 12/21/2022] [Accepted: 12/25/2022] [Indexed: 01/12/2023]
Abstract
AIM Acute-on-chronic liver failure (ACLF), a disease with poor prognosis, is reportedly caused by cellular senescence due to mitochondrial dysfunction. In this study, we described and analyzed the underlying mechanism of a novel approach for ACLF using ABT263/navitoclax (Navi) that selectively eliminates senescent cells. METHODS Irradiation-induced senescent hepatocytes were used for in vitro evaluation of the effects of Navi on ACLF (n = 6 for each group). Lipopolysaccharide- and carbon tetrachloride-induced ACLF mouse model was used for in vivo evaluation of the effects of Navi administration compared with the control using one-way or two-way analysis of variance, followed by Student's t-test or Kruskal-Wallis test. The effects on the senescence-associated secretory phenotype (n = 8 for each group) and mitochondrial functions, including adenosine triphosphate concentration and membrane potential (n = 8 for each group), were investigated using real-time polymerase chain reaction, immunohistochemistry, and enzyme analysis. RESULTS Navi eliminated irradiation-induced senescent hepatocytes in vitro, leading to non-senescent hepatocyte proliferation. Navi eliminated senescent cells in the liver in vivo, resulting in downregulation of mRNA expression of senescence-associated secretory phenotype factors, a decrease of liver enzymes, and upregulated proliferation of non-senescent cells in the liver. Regarding mitochondrial functional assessment in the liver, adenosine triphosphate concentration and membrane potential were upregulated after Navi administration in vitro and in vivo. CONCLUSIONS Navi may ameliorate ACLF damage by eliminating senescent cells in the liver, downregulating senescence-associated secretory phenotype factors, and upregulating mitochondrial functions. We believe that this novel approach using Navi will pave the way for ACLF treatment.
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Affiliation(s)
- Yusuke Watanabe
- Division of Preemptive Medicine for Digestive Disease and Healthy Active Life, School of Medicine, Niigata University, Niigata, Japan.,Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Hiroyuki Abe
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Naruhiro Kimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Yoshihisa Arao
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Natsuki Ishikawa
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Maeda Yuichiro
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Toru Setsu
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Akira Sakamaki
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Hiroteru Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Takeshi Yokoo
- Division of Preemptive Medicine for Digestive Disease and Healthy Active Life, School of Medicine, Niigata University, Niigata, Japan.,Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Kenya Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
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15
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Abstract
This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of liver support systems for adults with acute‐on‐chronic liver failure.
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16
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Watanabe Y, Osaki A, Waguri N, Tsuchiya A, Terai S. Prognostic study of acute-on-chronic liver failure patients: Usefulness of the fibrosis-4 index. Medicine (Baltimore) 2022; 101:e31328. [PMID: 36343064 PMCID: PMC9646499 DOI: 10.1097/md.0000000000031328] [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] [Indexed: 11/09/2022] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a syndrome characterized by an acute deterioration of liver function in cirrhotic patients. Since treatment of this condition is difficult, its prevention is of paramount importance. The predictors of ACLF are yet to be identified. To determine the prognosis of cirrhotic and ACLF patients, we conducted a retrospective study to analyze each parameter in ACLF patients. Cirrhotic patients with serum total-bilirubin level ≥5.0 mg/dL and prothrombin time (PT) value ≤40% after acute insults were diagnosed with ACLF, whereas patients who met one of the above criteria were diagnosed with extended type of ACLF (EX-ACLF). Overall, in this study, 18 ACLF and 16 EX-ACLF patients retrospectively investigated between 2008 and 2020, and each data was analyzed during and before acute insults. In the analysis during acute insults, renal and coagulation functions showed significant differences between the ACLF and EX-ACLF groups. Furthermore, the mortality rate in the ACLF group was higher than that in the EX-ACLF group. In the analysis before acute insults, aspartate aminotransferase (AST), Fibrosis-4 (FIB-4) index score, and AST to platelet ratio index (APRI) showed significant differences between the two groups. Among these, the FIB-4 index score correlated best with ACLF severity for identifying cirrhotic patients with poor prognosis. The FIB-4 index is the most useful predictor of ACLF severity. Careful management of cirrhotic patients with a high FIB-4 index score is considered beneficial to prevent ACLF occurrence.
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Affiliation(s)
- Yusuke Watanabe
- Division of Preemptive Medicine for Digestive Disease and Healthy Active Life, School of Medicine, Niigata University, Niigata, Japan
- Division of Gastroenterology and Hepatology, Niigata City General Hospital, Niigata, Japan
- *Correspondence: Yusuke Watanabe, Division of Preemptive Medicine for Digestive Disease and Healthy Active Life, School of Medicine, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan (e-mail: )
| | - Akihiko Osaki
- Division of Gastroenterology and Hepatology, Niigata City General Hospital, Niigata, Japan
| | - Nobuo Waguri
- Division of Gastroenterology and Hepatology, Niigata City General Hospital, Niigata, Japan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
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17
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Zhang T, Ye B, Shen J. Prognostic value of albumin-related ratios in HBV-associated decompensated cirrhosis. J Clin Lab Anal 2022; 36:e24338. [PMID: 35297102 PMCID: PMC8993660 DOI: 10.1002/jcla.24338] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 02/25/2022] [Accepted: 02/28/2022] [Indexed: 12/13/2022] Open
Abstract
Background Identification of effective and accurate prognostic biomarkers for hepatitis B virus‐associated decompensated cirrhosis (HBV‐DeCi) is challenging. This study was designed to determine and compare the prognostic value of albumin‐related ratios (blood urea nitrogen‐to‐albumin ratio [BAR], C‐reactive protein‐to‐albumin ratio [CAR], prothrombin time‐international normalized ratio‐to‐albumin ratio [PTAR], neutrophil count‐to‐albumin ratio [NAR], and D‐dimer‐to‐albumin ratio [DAR]) in HBV‐DeCi patients. Methods We retrospectively recruited 161 HBV‐DeCi patients. Receiver operating characteristic curve, DeLong test, and Cox regression analyses were used to estimate and compare the predictive value of these five albumin‐related ratios and Model for End‐Stage Liver Disease (MELD) score. Results A total of 29 (18.0%) patients had died 30 days after admission. The prognostic roles of CAR, DAR, PTAR, NAR, and BAR in HBV‐DeCi were different. CAR, PTAR, NAR, and BAR were significantly higher in non‐survivors compared with survivors. However, DAR did not differ between the two groups. The predictive power of BAR was superior to that of the other four albumin‐related biomarkers and similar to that of MELD score. On multivariate analysis, BAR and MELD score were identified as independent prognostic factors, and the combination of BAR and MELD score may improve the prognostic accuracy in HBV‐DeCi. Conclusion The present findings suggest that BAR may be a simple and useful prognostic tool to predict mortality in HBV‐DeCi patients.
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Affiliation(s)
- Tan Zhang
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
| | - Bin Ye
- Department of Critical Care Medicine, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
| | - JianJiang Shen
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
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18
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Choudhury A, Vijayaraghavan R, Maiwall R, Kumar M, Duan Z, Yu C, Hamid SS, Jafri W, Butt AS, Devarbhavi H, Ning Q, Ma K, Tan SS, Shukla A, Dhiman R, Duseja A, Taneja S, Eapen CE, Goel A, Treeprasertsuk S, Al-Mahtab M, Ghazinyan H, Kim DJ, Sahu MK, Lee GH, Lesmana LA, Lesmana RC, Shah S, Abbas Z, Sollano JD, Rao PN, Kulkarni A, Shiha G, Shrestha A, Dokmeci AK, Yuen MF, Payawal DA, Kalista KF, Prasad VGM, Lau GK, Karim F, Jain P, Kumar G, Arora V, Pamecha V, Sinha P, Sarin SK. 'First week' is the crucial period for deciding living donor liver transplantation in patients with acute-on-chronic liver failure. Hepatol Int 2021; 15:1376-1388. [PMID: 34608586 DOI: 10.1007/s12072-021-10206-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Accepted: 04/30/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Acute-on-chronic liver failure (ACLF) is a rapidly progressive illness with high short-term mortality. Timely liver transplant (LT) may improve survival. We evaluated various indices for assessment of the severity of liver failure and their application for eligibility and timing of living donor LT (LDLT). METHODS Altogether 1021 patients were analyzed for the severity and organ failure at admission to determine transplant eligibility and 28 day survival with or without transplant. RESULTS The ACLF cohort [mean age 44 ± 12.2 years, males 81%) was of sick patients; 55% willing for LT at admission, though 63% of them were ineligible due to sepsis or organ failure. On day 4, recovery in sepsis and/or organ failure led to an improvement in transplant eligibility from 37% at baseline to 63.7%. Delay in LT up to 7 days led to a higher incidence of multiorgan failure (p < 0.01) contributing to 23% of the first week and 55% of all-cause 28-day mortality. In a matched cohort analysis, the actuarial survival with LT (n = 41) and conditional survival in the absence of transplant (n = 191) were comparable, when the condition, i.e., transplant was adjusted. The comparison curve showed differentiation in survival beyond 7 days (p < 0.01). CONCLUSIONS ACLF is a rapidly progressive disease and risk stratification within the first week of hospitalization is needed. 'Emergent LT' should be defined in the first week in the ACLF patients; the transplant window for improving survival in a live donor setting.
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Affiliation(s)
- Ashok Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.,Department of Transplant, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rajan Vijayaraghavan
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.,Department of Transplant, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.,Department of Transplant, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.,Department of Transplant, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Zhongping Duan
- Translational Hepatology Institute Capital Medical University, Beijing You'an Hospital, Beijing, China
| | - Chen Yu
- Translational Hepatology Institute Capital Medical University, Beijing You'an Hospital, Beijing, China
| | - Saeed Sadiq Hamid
- Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Wasim Jafri
- Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Amna Subhan Butt
- Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Harshad Devarbhavi
- Department of Gastroenterology and Hepatology, St John Medical College, Bangalore, India
| | - Qin Ning
- Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ke Ma
- Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Soek-Siam Tan
- Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia
| | - Akash Shukla
- Department of Hepatology, KEM Hospital and Seth GSMC, Mumbai, India
| | - Radhakrishna Dhiman
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ajay Duseja
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Sunil Taneja
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - C E Eapen
- Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | - Ashish Goel
- Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India
| | | | - Mamun Al-Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Hasmik Ghazinyan
- Department of Hepatology, Nork Clinical Hospital of Infectious Diseases, Yerevan, Armenia
| | - Dong Joon Kim
- Centre for Liver and Digestive Diseases, Gangwon-Do, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon, Republic of Korea
| | - Manoj K Sahu
- Department of Gastroenterology and Biliary Sciences, IMS and SUM Hospital, Bhubaneswar, Odisha, India
| | - Guan Huei Lee
- Department of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
| | | | | | - Samir Shah
- Department of Hepatology, Global Hospital, Mumbai, India
| | - Zaigham Abbas
- Department of Hepatogastroenterology, Ziauddin University, Karachi, Pakistan
| | - Jose D Sollano
- Department of Hepatology, Cardinal Santos Medical Centre, Manila, Philippines
| | - P N Rao
- Asian Institute of Gastroenterology, Hyderabad, India
| | | | - Gamal Shiha
- Department of Internal Medicine, Egyptian Liver Research Institute and Hospital, Cairo, Egypt
| | | | - AKadir Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Man Fung Yuen
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | | | - Kemal Fariz Kalista
- Division of Hepatobiliary Cipto Mangunkusuamo Hospital, University of Indonesia, Jakarta, Indonesia
| | | | - George K Lau
- Department of Gastroenterology, Humanity and Health Medical Centre, Hong Kong, China
| | - Fazal Karim
- Department of Hepatology, Sir Salimullah Medical College, Dhaka, Bangladesh
| | - Priyanka Jain
- Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guresh Kumar
- Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vinod Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.,Department of Transplant, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Viniyendra Pamecha
- Department of Hepatobiliary Surgery, Institute of Liver and Biliary Sciences, New Delhi, India.,Department of Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Piyush Sinha
- Department of Hepatobiliary Surgery, Institute of Liver and Biliary Sciences, New Delhi, India.,Department of Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India. .,Department of Transplant, Institute of Liver and Biliary Sciences, New Delhi, India.
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19
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Noh BG, Lee N, Lee BC, Yoon M. Selected deceased donor liver transplantation in controlled Fournier's gangrene: a case report. KOREAN JOURNAL OF TRANSPLANTATION 2021; 35:195-199. [PMID: 35769247 PMCID: PMC9235450 DOI: 10.4285/kjt.21.0013] [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: 06/07/2021] [Revised: 07/26/2021] [Accepted: 07/27/2021] [Indexed: 11/21/2022] Open
Abstract
Bacterial infection represents a turning point in the natural history of cirrhosis, causing the development of acute-on-chronic liver failure. It significantly affects the outcome of patients listed for liver transplantation. We report the case of a 57-year-old man who had been regularly treated for hepatitis B virus, alcoholic liver cirrhosis, and hepatic failure. The patient was hospitalized again due to variceal bleeding and hepatic coma. He visited the emergency room with painful anal swelling, dysuria, icteric sclera, and serious abdominal distension. The painful anal swelling and necrosis progressed; thus, he was diagnosed with Fournier's gangrene. Enterococcus faecium and Candida albicans were detected in the blood. Gangrene wound debris was studied extensively. Despite appropriate antibiotic treatment, vancomycin-resistant enterococcus and C. albicans were continuously present in the blood. Wide debridement of the wound and T-colostomy were performed. After this, norepinephrine and vasopressin were used to maintain stable vital signs. It was difficult to establish a liver transplant operation. Despite repeated bleeding, bacterial infections improved with additional antibiotics. Finally, selected deceased donor liver transplantation in controlled Fournier's gangrene was successfully performed. Controlled infections may be allowed in transplantation surgery.
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Affiliation(s)
- Byeong Gwan Noh
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Hospital, Busan, Korea
| | - Nuri Lee
- Department of Surgery, Veterans Health Service Medical Center, Seoul, Korea
| | - Byoung Chul Lee
- Division of Colorectal Surgery, Department of Surgery, Pusan National University Hospital, Busan, Korea
| | - Myunghee Yoon
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
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20
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Liu X, Xu J. Calling a stage-based treatment model for chronic liver diseases in China mainland. Ann Hepatol 2021; 19:585-589. [PMID: 31711913 DOI: 10.1016/j.aohep.2019.09.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 09/21/2019] [Indexed: 02/04/2023]
Abstract
China is regarded as the "leader in liver diseases" because that one-fifth of the population was affected by some forms of liver diseases in this developing country. In addition to common infectious liver diseases (such as viral hepatitis and parasitic liver diseases), non-infectious liver diseases such as fatty liver diseases (FLD), drug-induced liver injury (DILI), alcoholic liver diseases (ALD), autoimmune liver diseases (AILD), vessel-related liver diseases, genetic metabolic liver diseases and liver masses are present. In recent years, an increasing number of liver diseases have been reported in special populations, including childhood liver diseases, pregnancy-related liver diseases and liver transplant-associated diseases and so on. Absence of characteristic symptoms and signs coupled with a lack of medical knowledge, patients with chronic liver diseases seek medical treatment without a reliable model, which resulted to the chaotic consult medical status in China mainland. This article aims to describe the current seek medical status of chronic liver diseases and discuss a stage-based consulting medical model for chronic liver diseases in China mainland, which would contribute to make rational use of limited medical resources and help to address National Health China 2030 strategy initiated by the Chinese government.
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Affiliation(s)
- Xueqin Liu
- Department of Hepatology & Translation Medicine, Fuling Center Hospital of Chongqing City, Chongqing, China
| | - Jian Xu
- Department of Hepatology & Translation Medicine, Fuling Center Hospital of Chongqing City, Chongqing, China.
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21
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Zanetto A, Shalaby S, Gambato M, Germani G, Senzolo M, Bizzaro D, Russo FP, Burra P. New Indications for Liver Transplantation. J Clin Med 2021; 10:3867. [PMID: 34501314 PMCID: PMC8432035 DOI: 10.3390/jcm10173867] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 08/20/2021] [Accepted: 08/27/2021] [Indexed: 12/12/2022] Open
Abstract
Liver transplantation (LT) is an important therapeutic option for the treatment of several liver diseases. Modern LT is characterized by remarkable improvements in post-transplant patient survival, graft survival, and quality of life. Thanks to these great improvements, indications for LT are expanding. Nowadays, clinical conditions historically considered exclusion criteria for LT, have been considered new indications for LT, showing survival advantages for patients. In this review, we provide an updated overview of the principal newer indications for LT, with particular attention to alcoholic hepatitis, acute-on-chronic liver failure (ACLF), cholangiocarcinoma and colorectal cancer metastases.
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Affiliation(s)
| | | | | | | | | | | | | | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery Oncology and Gastroenterology, University of Padova, Via Giustiniani 2, 35128 Padova, Italy; (A.Z.); (S.S.); (M.G.); (G.G.); (M.S.); (D.B.); (F.P.R.)
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22
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Bone Marrow Mesenchymal Stem Cells in Acute-on-Chronic Liver Failure Grades 2 and 3: A Phase I-II Randomized Clinical Trial. Can J Gastroenterol Hepatol 2021; 2021:3662776. [PMID: 34395335 PMCID: PMC8357501 DOI: 10.1155/2021/3662776] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 07/24/2021] [Indexed: 12/16/2022] Open
Abstract
INTRODUCTION Acute-on-chronic liver failure (ACLF) is an acute liver decompensation in cirrhotic patients, which leads to organ failures and high short-term mortality. The treatment is based on the management of complications and, in severe cases, liver transplantation. Since specific treatment is unavailable, we aimed to evaluate the safety and initial efficacy of bone marrow mesenchymal stem cells (BM-MSC) in patients with ACLF Grades 2 and 3, a population excluded from previous clinical trials. METHODS This is a randomized placebo-controlled phase I-II single center study, which enrolled 9 cirrhotic patients from 2018 to 2020, regardless of the etiology. The control group (n = 5) was treated with standard medical therapy (SMT) and placebo infusion of saline. The intervention group (n = 4) received SMT plus 5 infusions of 1 × 106 cells/kg of BM-MSC for 3 weeks. Both groups were monitored for 90 days. A Chi-square test was used for qualitative variables, and the t-test and Mann-Whitney U test for quantitative variables. The Kaplan-Meier estimator was used to build survival curves. In this study, we followed the intention-to-treat analysis, with a significance of 5%. RESULTS Nine patients with a mean Child-Pugh (CP) of 12.3, MELD of 38.4, and CLIF-C score of 50.7 were recruited. Hepatitis C and alcohol were the main etiologies. The average infusion per patient was 2.9 and only 3 patients (2 in control and 1 in the BM-MSC group) received all the protocol infusions. There were no infusion-related side effects, although one patient in the intervention group presented hypernatremia and a gastric ulcer, after the third and fifth infusions, respectively. The survival rate after 90 days was 20% (1/5) for placebo versus 25% (1/4) for the BM-MSC. The patient who completed the entire MSC protocol showed a significant improvement in CP (C-14 to B-9), MELD (32 to 22), and ACLF (grade 3 to 0). CONCLUSION BM-MSC infusion is safe and feasible in patients with ACLF Grades 2 and 3.
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23
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Wang F, Sun W, Xiao Q, Liang C, Jiang S, Lian Y, Shao J, Tan S, Zheng S. Peripheral T lymphocytes predict the severity and prognosis in patients with HBV-related acute-on-chronic liver failure. Medicine (Baltimore) 2021; 100:e24075. [PMID: 33592861 PMCID: PMC7870253 DOI: 10.1097/md.0000000000024075] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Accepted: 12/02/2020] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening syndrome with high mortality. Biomarkers are urgently needed to predict the prognosis of HBV-ACLF. Recent evidence suggests a key role for immune system in the pathology of HBV-ACLF. Here, we analyzed the correlation between peripheral blood T lymphocytes and the severity and prognosis in HBV-ACLF patients. METHOD Sixty-six patients with HBV-ACLF received conventional medical treatments for 4 weeks. Twenty-five healthy subjects and 20 HBV patients were enrolled for comparison. We determined white blood cell count, lymphocytes, CD3+, CD4+ and CD8+ T cells, and CD4+CD25+ Treg cells in the blood of all subjects. Their associations with laboratory parameters before or after treatments were statistically analyzed. RESULT The results showed that compare normal subjects and chronic hepatitis B patients, HBV-ACLF patients had significantly increased white blood count, CD4+ T cells and decreased lymphocytes, CD3+ T cells, and Treg cells. Correlation analysis showed that white blood cell, lymphocytes, and peripheral T lymphocytes were correlated with prothrombin activity (PTA) and model for end-stage liver disease (MELD) scores. After treatment, white blood cell, lymphocytes, and peripheral T lymphocytes were also correlated with PTA and MELD scores. Additionally, total bilirubin (TBIL), alanine aminotransferase (ALT), international standard ratio (INR), MELD, and white blood cell count were potential prognostic criteria for HBV-ACLF patients. CONCLUSION HBV-ACLF patients had depletion and dysfunction of immune system. Changes of peripheral T lymphocytes were closely related to the pathogenesis and prognosis of disease. Our results may contribute to predict the severity of HBV-ACLF, and provide a prognosis response to improve the treatment of HBV-ACLF.
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Affiliation(s)
- Feixia Wang
- Department of Integrated TCM and Western Medicine, The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Weiwei Sun
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Qian Xiao
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Chongfeng Liang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Shulian Jiang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yanan Lian
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jiangjuan Shao
- Department of Integrated TCM and Western Medicine, The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine
| | - Shanzhong Tan
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Shizhong Zheng
- Department of Integrated TCM and Western Medicine, The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
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24
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Trebicka J, Sundaram V, Moreau R, Jalan R, Arroyo V. Liver Transplantation for Acute-on-Chronic Liver Failure: Science or Fiction? Liver Transpl 2020; 26:906-915. [PMID: 32365422 DOI: 10.1002/lt.25788] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 04/02/2020] [Accepted: 04/05/2020] [Indexed: 12/17/2022]
Abstract
Acute clinical deterioration of a patient with chronic liver disease remains a decisive time point both in terms of medical management and prognosis. This condition, also known as acute decompensation (AD), is an important event determining a crossroad in the trajectory of patients. A significant number of patients with AD may develop hepatic or extrahepatic organ failure, or both, which defines the syndrome acute-on-chronic liver failure (ACLF), and ACLF is associated with a high morbidity and short-term mortality. ACLF may occur at any phase during chronic liver disease and is pathogenetically defined by systemic inflammation and immune metabolic dysfunction. When organ failures develop in the presence of cirrhosis, especially extrahepatic organ failures, liver transplantation (LT) may be the only curative treatment. This review outlines the evidence supporting LT in ACLF patients, highlighting the role of timing, bridging to LT, and possible indicators of futility. Importantly, prospective studies on ACLF and transplantation are urgently needed.
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Affiliation(s)
- Jonel Trebicka
- Translational Hepatology, Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany.,European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain.,Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.,Institute for Bioengineering of Catalonia, Barcelona, Spain
| | - Vinay Sundaram
- Division of Gastroenterology and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Richard Moreau
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain.,U1149, Centre de Recherche sur l'Inflammation, UMRS1149 Université de Paris, INSERM, Paris, France.,Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France
| | - Rajiv Jalan
- Translational Hepatology, Department of Internal Medicine I, Goethe University Clinic Frankfurt, Frankfurt, Germany.,Royal Free Hospital, London, United Kingdom
| | - Vicente Arroyo
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
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25
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Niewiński G, Morawiec S, Janik MK, Grąt M, Graczyńska A, Zieniewicz K, Raszeja-Wyszomirska J. Acute-On-Chronic Liver Failure: The Role of Prognostic Scores in a Single-Center Experience. Med Sci Monit 2020; 26:e922121. [PMID: 32415953 PMCID: PMC7249742 DOI: 10.12659/msm.922121] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Background Acute-on-chronic liver failure (ACLF) is associated with multi-organ failure and high short-term mortality. We evaluated the role of currently available prognostic scores for prediction of 90-day mortality in ACLF patients. Material/Methods Fifty-five (M/F=40/15, mean age 60.0±11.1years) consecutive cirrhotic patients with severe liver insufficiency (mean MELD 28.4±9.0, Child-Pugh score – C-12) were enrolled into the study. MELD variants and SOFA, CLIF-SOFA, and CLIF-C scores were calculated, mortality predicting factors were identified, and clinical comparisons between ACLF and AD patients were performed. Results In total, 30 (55%) patients were transplanted (22 ACLF and 8 AD), and 20 (30%) died (19 ACLF and 1 AD). Five (9%) patients survived without liver transplantation (LT) (3 ACLF and 2 AD), and 3 transplant recipients died within 1 month. SOFA, CLIF-SOFA, CLIF-C OF, and INR were significantly associated with the incidence of 90-day mortality in competing risk regression analysis (all p<0.001). The model based on SOFA had the lowest BIC, with the optimal cut-off for 90-day mortality prediction ≥12, with the area under the receiver operating characteristic (AUROC) of 0.901 (95% CI 0.779–1.000; p<0.001), and corresponding incidence of transplantation rates of 85.5% and 11.8%, respectively (p<0.001). Of note, the important role of 24-h urine output is emphasized. Conclusions In this series of ACLF patients, SOFA score outperformed the CLIF-C scores in predicting 90-day mortality. Multi-organ failure scores performed better in predicting patient mortality than conventional liver function assessment. LT is possible and remains effective in selected ACLF patients.
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Affiliation(s)
- Grzegorz Niewiński
- II Department of Anesthesiology and Intensive Care, Medical University of Warsaw, Warsaw, Poland
| | - Szymon Morawiec
- II Department of Anesthesiology and Intensive Care, Medical University of Warsaw, Warsaw, Poland
| | - Maciej K Janik
- Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Michał Grąt
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Agata Graczyńska
- II Department of Anesthesiology and Intensive Care, Medical University of Warsaw, Warsaw, Poland
| | - Krzysztof Zieniewicz
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Joanna Raszeja-Wyszomirska
- Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
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26
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Impact of acute-on-chronic liver failure on post-transplant survival and on kidney outcomes. Eur J Gastroenterol Hepatol 2019; 31:1157-1164. [PMID: 31385871 DOI: 10.1097/meg.0000000000001467] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES We aimed to evaluate the effect of acute-on-chronic liver failure (ACLF) on patients' 1-year post-liver transplant (LT) survival. In addition, we evaluated the effect of ACLF on the development of post-LT chronic kidney disease (CKD) and early allograft dysfunction (EAD). PATIENTS AND METHODS A retrospective cohort of patients who underwent transplantation from 2010 to 2016 was studied. EASL-CLIF's definition of ACLF was used. The risk of post-LT death, CKD, and EAD was estimated with regression models weighted by inverse probability weighting considering the recipients' characteristics. Donor's BMI and donor risk index were included in the models as well. RESULTS A total of 185 patients were included: 125 (67.6%) without ACLF and 60 (32.4%) with ACLF. The 1-year post-LT survival rate was 91.2% [95% confidence interval (CI): 84.6-95.1%] in patients without ACLF versus 84.9% (95% CI: 73.1-91.9%) in patients with ACLF. Post-LT CKD occurred in 43 (38.7%) patients without ACLF versus 26 (52.0%) patients with ACLF. EAD occurred in 40 (32.3%) patients without ACLF versus 15 (28.8%) patients with ACLF. No effect of ACLF was found on survival (hazard ratio 1.75; 95% CI: 0.64-4.75, P = 0.272), CKD (odds ratio: 1.31; 95% CI: 0.60-2.86; P = 0.491), or EAD (odds ratio: 0.74; 95% CI: 0.38-1.66, P = 0.473). CONCLUSION In this study, which included mainly patients with grade 1 ACLF at the time of LT, its presence had no impact on post-LT survival or on the occurrence of CKD or EAD.
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Sarin SK, Choudhury A, Sharma MK, Maiwall R, Al Mahtab M, Rahman S, Saigal S, Saraf N, Soin AS, Devarbhavi H, Kim DJ, Dhiman RK, Duseja A, Taneja S, Eapen CE, Goel A, Ning Q, Chen T, Ma K, Duan Z, Yu C, Treeprasertsuk S, Hamid SS, Butt AS, Jafri W, Shukla A, Saraswat V, Tan SS, Sood A, Midha V, Goyal O, Ghazinyan H, Arora A, Hu J, Sahu M, Rao PN, Lee GH, Lim SG, Lesmana LA, Lesmana CR, Shah S, Prasad VGM, Payawal DA, Abbas Z, Dokmeci AK, Sollano JD, Carpio G, Shresta A, Lau GK, Fazal Karim M, Shiha G, Gani R, Kalista KF, Yuen MF, Alam S, Khanna R, Sood V, Lal BB, Pamecha V, Jindal A, Rajan V, Arora V, Yokosuka O, Niriella MA, Li H, Qi X, Tanaka A, Mochida S, Chaudhuri DR, Gane E, Win KM, Chen WT, Rela M, Kapoor D, Rastogi A, Kale P, Rastogi A, Sharma CB, Bajpai M, Singh V, Premkumar M, Maharashi S, Olithselvan A, Philips CA, Srivastava A, Yachha SK, Wani ZA, Thapa BR, Saraya A, Shalimar, Kumar A, Wadhawan M, Gupta S, Madan K, Sakhuja P, Vij V, Sharma BC, Garg H, Garg V, Kalal C, et alSarin SK, Choudhury A, Sharma MK, Maiwall R, Al Mahtab M, Rahman S, Saigal S, Saraf N, Soin AS, Devarbhavi H, Kim DJ, Dhiman RK, Duseja A, Taneja S, Eapen CE, Goel A, Ning Q, Chen T, Ma K, Duan Z, Yu C, Treeprasertsuk S, Hamid SS, Butt AS, Jafri W, Shukla A, Saraswat V, Tan SS, Sood A, Midha V, Goyal O, Ghazinyan H, Arora A, Hu J, Sahu M, Rao PN, Lee GH, Lim SG, Lesmana LA, Lesmana CR, Shah S, Prasad VGM, Payawal DA, Abbas Z, Dokmeci AK, Sollano JD, Carpio G, Shresta A, Lau GK, Fazal Karim M, Shiha G, Gani R, Kalista KF, Yuen MF, Alam S, Khanna R, Sood V, Lal BB, Pamecha V, Jindal A, Rajan V, Arora V, Yokosuka O, Niriella MA, Li H, Qi X, Tanaka A, Mochida S, Chaudhuri DR, Gane E, Win KM, Chen WT, Rela M, Kapoor D, Rastogi A, Kale P, Rastogi A, Sharma CB, Bajpai M, Singh V, Premkumar M, Maharashi S, Olithselvan A, Philips CA, Srivastava A, Yachha SK, Wani ZA, Thapa BR, Saraya A, Shalimar, Kumar A, Wadhawan M, Gupta S, Madan K, Sakhuja P, Vij V, Sharma BC, Garg H, Garg V, Kalal C, Anand L, Vyas T, Mathur RP, Kumar G, Jain P, Pasupuleti SSR, Chawla YK, Chowdhury A, Alam S, Song DS, Yang JM, Yoon EL. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update. Hepatol Int 2019; 13:353-390. [PMID: 31172417 PMCID: PMC6728300 DOI: 10.1007/s12072-019-09946-3] [Show More Authors] [Citation(s) in RCA: 546] [Impact Index Per Article: 91.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2019] [Accepted: 04/03/2019] [Indexed: 02/07/2023]
Abstract
The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the "APASL ACLF Research Consortium (AARC)" was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the 'Golden Therapeutic Window', extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here.
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Affiliation(s)
- Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.
| | - Ashok Choudhury
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Manoj K Sharma
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Salimur Rahman
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Sanjiv Saigal
- Department of Hepatology, Medanta The Medicity, Gurgaon, India
| | - Neeraj Saraf
- Department of Hepatology, Medanta The Medicity, Gurgaon, India
| | - A S Soin
- Department of Hepatology, Medanta The Medicity, Gurgaon, India
| | | | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Seoul, South Korea
| | - R K Dhiman
- Department of Hepatology, PGIMER, Chandigarh, India
| | - Ajay Duseja
- Department of Hepatology, PGIMER, Chandigarh, India
| | - Sunil Taneja
- Department of Hepatology, PGIMER, Chandigarh, India
| | - C E Eapen
- Department of Hepatology, CMC, Vellore, India
| | - Ashish Goel
- Department of Hepatology, CMC, Vellore, India
| | - Q Ning
- Institute and Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Chen
- Translational Hepatology Institute Capital Medical University, Beijing You'an Hospital, Beijing, China
| | - Ke Ma
- Institute and Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Z Duan
- Translational Hepatology Institute Capital Medical University, Beijing You'an Hospital, Beijing, China
| | - Chen Yu
- Translational Hepatology Institute Capital Medical University, Beijing You'an Hospital, Beijing, China
| | | | - S S Hamid
- Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Amna S Butt
- Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Wasim Jafri
- Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Akash Shukla
- Department of Gastroenterology, Lokmanya Tilak Municipal General Hospital and Lokmanya Tilak Municipal Medical College, Sion, Mumbai, India
| | | | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Bata Caves, Selangor, Malaysia
| | - Ajit Sood
- Department of Gastroenterology, DMC, Ludhiana, India
| | - Vandana Midha
- Department of Gastroenterology, DMC, Ludhiana, India
| | - Omesh Goyal
- Department of Gastroenterology, DMC, Ludhiana, India
| | - Hasmik Ghazinyan
- Department of Hepatology, Nork Clinical Hospital of Infectious Disease, Yerevan, Armenia
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital and GRIPMER, New Delhi, Delhi, India
| | - Jinhua Hu
- Department of Medicine, 302 Millitary Hospital, Beijing, China
| | - Manoj Sahu
- Department of Gastroenterology and Hepatology Sciences, IMS & SUM Hospital, Bhubaneswar, Odisha, India
| | - P N Rao
- Asian Institute of Gastroenterology, Hyderabad, India
| | - Guan H Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | - Seng G Lim
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
| | | | | | - Samir Shah
- Department of Hepatology, Global Hospitals, Mumbai, India
| | | | - Diana A Payawal
- Fatima University Medical Center Manila, Manila, Philippines
| | - Zaigham Abbas
- Department of Medicine, Ziauddin University Hospital, Karachi, Pakistan
| | - A Kadir Dokmeci
- Department of Medicine, Ankara University School of Medicine, Ankara, Turkey
| | - Jose D Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Gian Carpio
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Ananta Shresta
- Department of Hepatology, Foundation Nepal Sitapaila Height, Kathmandu, Nepal
| | - G K Lau
- Department of Medicine, Humanity and Health Medical Group, New Kowloon, Hong Kong, China
| | - Md Fazal Karim
- Department of Hepatology, Sir Salimullah Medical College, Dhaka, Bangladesh
| | - Gamal Shiha
- Egyptian Liver Research Institute And Hospital, Cairo, Egypt
| | - Rino Gani
- Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine, Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Kemal Fariz Kalista
- Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine, Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Man-Fung Yuen
- Department of Medicine, Queen Mary Hospital Hong Kong, The University of Hong Kong, Hong Kong, China
| | - Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | - Rajeev Khanna
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | - Vikrant Sood
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | - Bikrant Bihari Lal
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | - Viniyendra Pamecha
- Department of Hepatobilliary Pancreatic Surgery and Liver Transplant, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - V Rajan
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | - Vinod Arora
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
| | | | | | - Hai Li
- Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaolong Qi
- CHESS Frontier Center, The First Hospital of Lanzhou University, Lanzhou University, Lanzhou, China
| | - Atsushi Tanaka
- Department of Medicine, Tokyo University School of Medicine, Tokyo, Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Saitama, Japan
| | | | - Ed Gane
- New Zealand Liver Transplant Unit, Auckland Hospital, Auckland, New Zealand
| | | | - Wei Ting Chen
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Medical Foundation, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Mohd Rela
- Department of Liver Transplant Surgery, Dr. Rela Institute and Medical Centre, Chennai, India
| | | | - Amit Rastogi
- Department of Hepatology, Medanta The Medicity, Gurgaon, India
| | - Pratibha Kale
- Department of Microbiology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | - Archana Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | - Chhagan Bihari Sharma
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | - Meenu Bajpai
- Department of Immunohematology and Transfusion Medicine, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
| | | | | | | | - A Olithselvan
- Division of Liver Transplantation and Hepatology, Manipal Hospitals, Bangalore, India
| | - Cyriac Abby Philips
- The Liver Unit, Cochin Gastroenterology Group, Ernakulam Medical Centre, Kochi, India
| | - Anshu Srivastava
- Department of Pediatric Gastroenterology, SGPGIMS, Lucknow, India
| | | | | | - B R Thapa
- Department of Gastroenterology and Pediatric Gastroenterology, PGIMER, Chandigarh, India
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition, AIIMS, New Delhi, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition, AIIMS, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital and GRIPMER, New Delhi, Delhi, India
| | - Manav Wadhawan
- Department of Gastroenterology, Hepatology and Liver Transplant, B L K Hospital, New Delhi, India
| | - Subash Gupta
- Centre for Liver and Biliary Science, Max Hospital, New Delhi, India
| | - Kaushal Madan
- Department of Gastroenterology, Hepatology and Liver Transplant, Max Hospital, New Delhi, India
| | - Puja Sakhuja
- Department of Pathology, GB Pant Hospital, New Delhi, India
| | - Vivek Vij
- Department of Liver Transplant and Hepatobilliary Surgery, Fortis Hospital, New Delhi, India
| | - Barjesh C Sharma
- Department of Gastroenterology, GB Pant Hospital, New Delhi, India
| | - Hitendra Garg
- Department of Gastroenterology, Hepatology and Liver Transplant, Apollo Hospital, New Delhi, India
| | - Vishal Garg
- Department of Gastroenterology, Hepatology and Liver Transplant, Apollo Hospital, New Delhi, India
| | - Chetan Kalal
- Department of Hepatology, Sir H N Reliance Hospital and Research Centre, Mumbai, India
| | - Lovkesh Anand
- Department of Gastroenterology and Hepatology, Narayana Hospital, Gurugram, India
| | - Tanmay Vyas
- Department of Hepatology, Parimal Multi-Speciality Hospital, Ahmedabad, India
| | - Rajan P Mathur
- Department of Nephrology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Guresh Kumar
- Department of Statistics and Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Priyanka Jain
- Department of Statistics and Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Samba Siva Rao Pasupuleti
- Department of Statistics and Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Yogesh K Chawla
- Department of Hepatology and Gastroenterology, Kalinga Institute of Med Sciences, KIIT University, Bhubaneswar, India
| | - Abhijit Chowdhury
- Department of Hepatology, Institute of Post Graduate Medical Education and Research, Kolkata, India
| | - Shahinul Alam
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Do Seon Song
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Eileen L Yoon
- Department Of Internal Medicine, Inje University College of Medicine, Busan, South Korea
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Artzner T, Michard B, Besch C, Levesque E, Faitot F. Liver transplantation for critically ill cirrhotic patients: Overview and pragmatic proposals. World J Gastroenterol 2018; 24:5203-5214. [PMID: 30581269 PMCID: PMC6295835 DOI: 10.3748/wjg.v24.i46.5203] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Revised: 11/12/2018] [Accepted: 11/13/2018] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation for critically ill cirrhotic patients with acute deterioration of liver function associated with extrahepatic organ failures is controversial. While transplantation has been shown to be beneficial on an individual basis, the potentially poorer post-transplant outcome of these patients taken as a group can be held as an argument against allocating livers to them. Although this issue concerns only a minority of liver transplants, it calls into question the very heart of the allocation paradigms in place. Indeed, most allocation algorithms have been centered on prioritizing the sickest patients by using the model for end-stage liver disease score. This has led to allocating increasing numbers of livers to increasingly critically ill patients without setting objective or consensual limits on how sick patients can be when they receive an organ. Today, finding robust criteria to deem certain cirrhotic patients too sick to be transplanted seems urgent in order to ensure the fairness of our organ allocation protocols. This review starts by fleshing out the argument that finding such criteria is essential. It examines five types of difficulties that have hindered the progress of recent literature on this issue and identifies various strategies that could be followed to move forward on this topic, taking into account the recent discussion on acute on chronic liver failure. We move on to review the literature along four axes that could guide clinicians in their decision-making process regarding transplantation of critically ill cirrhotic patients.
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Affiliation(s)
- Thierry Artzner
- Service de Réanimation Médicale, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg 67000, France
| | - Baptiste Michard
- Service de Réanimation Médicale, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg 67000, France
- Service de Chirurgie Hépatobiliaire et Transplantation, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg 67000, France
| | - Camille Besch
- Service de Chirurgie Hépatobiliaire et Transplantation, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg 67000, France
| | - Eric Levesque
- Service d’Anesthésie et Réanimation Chirurgicale, Hôpital Henri Mondor, Créteil 94000, France
| | - François Faitot
- Service de Chirurgie Hépatobiliaire et Transplantation, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg 67000, France
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Fernández J, Saliba F. Liver transplantation in patients with ACLF and multiple organ failure: Time for priority after initial stabilization. J Hepatol 2018; 69:1004-1006. [PMID: 30241881 DOI: 10.1016/j.jhep.2018.09.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Revised: 09/03/2018] [Accepted: 09/04/2018] [Indexed: 12/30/2022]
Affiliation(s)
- Javier Fernández
- Liver ICU, Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain; Institut d'Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS), Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Spain; European Foundation of Chronic Liver Failure (EF-Clif), Barcelona, Spain
| | - Faouzi Saliba
- AP-HP, Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France; Université Paris Sud and University Paris Saclay, Paris XI, France; Unité INSERM U 935 and U 1193, Villejuif, France.
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Singanayagam A, Bernal W. Transplantation for the Very Sick Patient—Donor and Recipient Factors. CURRENT TRANSPLANTATION REPORTS 2018. [DOI: 10.1007/s40472-018-0197-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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Sarin SK, Choudhury A. Management of acute-on-chronic liver failure: an algorithmic approach. Hepatol Int 2018; 12:402-416. [PMID: 30116993 DOI: 10.1007/s12072-018-9887-5] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 07/13/2018] [Indexed: 02/07/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is a distinct syndrome of liver failure in a patient with chronic liver disease presenting with jaundice, coagulopathy and ascites and/or hepatic encephalopathy, developing following an acute hepatic insult and associated with high 28-day mortality. The definition though lacks global consensus, excludes patients with known distinct entities such as acute liver failure and those with end-stage liver disease. The initial Systemic Inflammatory Response Syndrome (SIRS) because of cytokine storm in relation to acute insult and/or subsequent development of sepsis due to immunoparalysis leads to extrahepatic organ failure. These cascades of events progress through a 'Golden Window' period of about 7 days, subsequent to which majority of the patients develop complications, such as sepsis and extrahepatic organ failure. Prevention of sepsis, support of organs and management of organ failure (commonly hepatic, renal, cerebral, coagulation) and early referral for transplant is crucial. The APASL ACLF research consortium (AARC) liver failure score is a dynamic prognostic model for management decisions and is superior to existing models. Aggressive multidisciplinary approach can lead to a transplant-free survival in nearly half of the cases. The present review provides an algorithmic approach to management of organ failure, sepsis prevention, use of dynamic prognostic models for management decision and is aimed to improve the skills for managing and improving the outcomes of such critically ill patients.
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Affiliation(s)
- Shiv Kumar Sarin
- Department of Hepatology and Liver Transplant, Institute of Liver and Biliary Sciences, D-1, VasantKunj, New Delhi, 110070, India.
| | - Ashok Choudhury
- Department of Hepatology and Liver Transplant, Institute of Liver and Biliary Sciences, D-1, VasantKunj, New Delhi, 110070, India
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Sersté T, Cornillie A, Njimi H, Pavesi M, Arroyo V, Putignano A, Weichselbaum L, Deltenre P, Degré D, Trépo E, Moreno C, Gustot T. The prognostic value of acute-on-chronic liver failure during the course of severe alcoholic hepatitis. J Hepatol 2018. [PMID: 29524528 DOI: 10.1016/j.jhep.2018.02.022] [Citation(s) in RCA: 87] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS A better identification of factors predicting death is needed in alcoholic hepatitis (AH). Acute-on-chronic liver failure (ACLF) occurs during the course of liver disease and can be identified when AH is diagnosed (prevalent ACLF [pACLF]) or during follow-up (incidental ACLF [iACLF]). This study analyzed the impact of ACLF on outcomes in AH and the role of infection on the onset of ACLF and death. METHODS Patients admitted from July 2006 to July 2015 suffering from biopsy-proven severe (s)AH with a Maddrey discriminant function (mDF) ≥32 were included. Infectious episodes, ACLF, and mortality were assessed during a 168-day follow-up period. Results were validated on an independent cohort. RESULTS One hundred sixty-five patients were included. Mean mDF was 66.3 ± 20.7 and mean model for end-stage liver disease score was 26.8 ± 7.4. The 28-day cumulative incidence of death (CID) was 31% (95% CI 24-39%). Seventy-nine patients (47.9%) had pACLF. The 28-day CID without pACLF and with pACLF-1, pACLF-2, and pACLF-3 were 10.4% (95% CI 5.1-18.0), 30.8% (95% CI 14.3-49.0), 58.3% (95% CI 35.6-75.5), and 72.4% (95% CI 51.3-85.5), respectively, p <0.0001. Twenty-nine patients (17.5%) developed iACLF. The 28-day relative risk of death in patients developing iACLF was 41.87 (95% CI 5.2-335.1; p <0.001). A previous infection was the only independent risk factor for developing iACLF during the follow-up. Prevalence, incidence, and impact on prognosis of ACLF were confirmed in a validation cohort of 97 patients with probable sAH. CONCLUSIONS ACLF is frequent during the course of sAH and is associated with high mortality. Infection strongly predicts the development of ACLF in this setting. LAY SUMMARY In patients with chronic liver disease, an acute deterioration of liver function combined with single or multiple organ failures is known as acute-on-chronic liver failure. This study shows that acute-on-chronic liver failure is frequent during the course of severe alcoholic hepatitis. In severe alcoholic hepatitis, acute-on-chronic liver failure is associated with high mortality and frequently occurs after an infection.
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Affiliation(s)
- Thomas Sersté
- Liver Unit, Department of Gastroenterology and Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium; Department of Hepatogastroenterology, CHU Saint-Pierre, Bruxelles, Belgium.
| | - Alexia Cornillie
- Liver Unit, Department of Gastroenterology and Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Hassane Njimi
- Biomedical Statistics, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Marco Pavesi
- The EASL-CLIF Consortium, European Foundation-CLIF, Barcelona, Spain
| | - Vicente Arroyo
- The EASL-CLIF Consortium, European Foundation-CLIF, Barcelona, Spain
| | - Antonella Putignano
- Liver Unit, Department of Gastroenterology and Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Laura Weichselbaum
- Liver Unit, Department of Gastroenterology and Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Pierre Deltenre
- Liver Unit, Department of Gastroenterology and Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Delphine Degré
- Liver Unit, Department of Gastroenterology and Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Eric Trépo
- Liver Unit, Department of Gastroenterology and Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Christophe Moreno
- Liver Unit, Department of Gastroenterology and Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Thierry Gustot
- Liver Unit, Department of Gastroenterology and Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium; The EASL-CLIF Consortium, European Foundation-CLIF, Barcelona, Spain; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Bruxelles, Belgium; Inserm Unité 1149, Centre de Recherche sur l'inflammation (CRI), Paris, France; UMR S_1149, Université Paris Diderot, Paris, France.
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Obed A, Bashir A, Jarrad A. A Case of Live Donor Liver Transplantation in Acute-on-Chronic Liver Failure with Budd-Chiari Syndrome: Donor and Recipient with Antiphospholipid Antibody Syndrome. AMERICAN JOURNAL OF CASE REPORTS 2018; 19:767-772. [PMID: 29959308 PMCID: PMC6055578 DOI: 10.12659/ajcr.909694] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Patient: Female, 47 Final Diagnosis: Antiphospholipid antibody syndrome Symptoms: Liver failure • pneumonia • renal failure Medication: — Clinical Procedure: Live donor liver transplantation Specialty: Transplantology
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Affiliation(s)
- Aiman Obed
- Department of Hepatobiliary and Transplant Surgery, Jordan Hospital, Amman, Jordan
| | - Abdalla Bashir
- Department of General and Transplant Surgery, Jordan Hospital, Amman, Jordan
| | - Anwar Jarrad
- Department of Hepatology, Gastroenterology and Hepatobiliary/Transplant Unit, Jordan Hospital, Amman, Jordan
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Ampuero J. Acute-on-chronic liver failure: a time to step forward. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2018; 109:397-398. [PMID: 28537080 DOI: 10.17235/reed.2017.5054/2017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Acute-on-chronic liver failure (ACLF) is defined as a syndrome characterized by acute deterioration of liver function on a chronic liver disease, associated with extrahepatic organ failure and high short-term mortality (≥ 15%). This concept represents a disruption in the traditional spectrum of liver diseases, particularly in liver cirrhosis. ACLF may appear during liver disease ranging from compensated to long-standing cirrhosis. Despite the heterogeneity of definitions, it is clear that ACLF results from different types of precipitants in patients with underlying chronic liver disease, mimicking the prognosis of acute liver failure. In this scenario, some new prognostic scores have been proposed instead of MELD or Child-Pugh scores. In the current issue, a retrospective Portuguese study (N = 177) carried out by Barosa et al. explored the usefulness of CLIF scores identifying high mortality rates among cirrhotic patients suffering from ACLF5.
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Affiliation(s)
- Javier Ampuero
- UGC de Enfermedades Digestivas, Hospital Universitario Virgen del Rocío, España
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Ferrarese A, Zanetto A, Becchetti C, Sciarrone SS, Shalaby S, Germani G, Gambato M, Russo FP, Burra P, Senzolo M. Management of bacterial infection in the liver transplant candidate. World J Hepatol 2018; 10:222-230. [PMID: 29527258 PMCID: PMC5838441 DOI: 10.4254/wjh.v10.i2.222] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 12/29/2017] [Accepted: 01/24/2018] [Indexed: 02/06/2023] Open
Abstract
Bacterial infection (BI) is a common cause of impairment of liver function in patients with cirrhosis, especially in the liver transplant candidates. These patients share an immunocompromised state and increased susceptibility to develop community and hospital-acquired infections. The changing epidemiology of BI, with an increase of multidrug resistant strains, especially in healthcare-associated settings, represents a critical issue both in the waiting list and in the post-operative management. This review focused on the role played by BI in patients awaiting liver transplantation, evaluating the risk of drop-out from the waiting list, the possibility to undergo liver transplantation after recovery from infection or during a controlled infection.
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Affiliation(s)
- Alberto Ferrarese
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
| | - Alberto Zanetto
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
| | - Chiara Becchetti
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
| | - Salvatore Stefano Sciarrone
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
| | - Sarah Shalaby
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
| | - Giacomo Germani
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
| | - Francesco Paolo Russo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
| | - Marco Senzolo
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua 35128, Italy
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Wu J, Li YY, Hu JH, Jia L, Shi M, Meng FP, Li J, Zhao J, Wang FS, Meng QH. Differential characteristics and prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure defined by European Association for the Study of the Liver - Chronic Liver Failure criteria. Hepatol Res 2018; 48:153-164. [PMID: 28456135 DOI: 10.1111/hepr.12909] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2017] [Revised: 04/18/2017] [Accepted: 04/28/2017] [Indexed: 12/18/2022]
Abstract
AIM To determine the differential characteristics and prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) detected using Asian Pacific Association for the Study of the Liver (APASL) criteria and then classified using European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) criteria. METHODS We retrospectively reviewed 316 HBV-related APASL ACLF patients treated at Beijing 302 Hospital or Beijing You'An Hospital (both Beijing, China) between February 2015 and February 2016. Clinical characteristics and mortality rates were compared among patients with different EASL-CLIF ACLF severity grades (no ACLF, and ACLF grades 1-3). RESULTS According to the EASL-CLIF criteria, 138 patients had no ACLF, 123 had ACLF at enrollment, and 55 developed ACLF during hospitalization. Both 28-day and 90-day transplant-free mortality were dramatically lower in patients without EASL-CLIF ACLF (0.7% and 5.1%, respectively) than in patients with EASL-CLIF ACLF (40.7% and 63.2%, respectively; both P < 0.001). Liver failure rates were similar in patients with and without EASL-CLIF ACLF, but extrahepatic organ failure was rare in patients without EASL-CLIF ACLF. Baseline serum creatinine, new bacterial infection and new acute kidney injury during hospitalization, maximum rising rates of CLIF-C ACLF score, and Model for End-stage Liver Disease score were independent predictors of EASL-CLIF ACLF after enrollment. CONCLUSIONS The EASL-CLIF ACLF classification can accurately prognosticate the short-term mortality of patients with HBV-related APASL ACLF. It can also distinguish distinct clinical characteristics and prognoses in patients with and without EASL-CLIF ACLF.
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Affiliation(s)
- Juan Wu
- Department of Infectious Diseases, 302 Military Hospital of China - Peking University Teaching Hospital, Beijing, China
| | - Yuan-Yuan Li
- Department of Infectious Diseases, 302 Military Hospital of China - Peking University Teaching Hospital, Beijing, China
| | - Jin-Hua Hu
- Medical Center for Liver Failure, Beijing 302 Hospital, Beijing, China
| | - Lin Jia
- Department of Critical Care Medicine of Liver Disease, Beijing You'An Hospital, Capital Medical University, Beijing, China
| | - Ming Shi
- Department of Infectious Diseases, 302 Military Hospital of China - Peking University Teaching Hospital, Beijing, China
| | - Fan-Ping Meng
- Department of Infectious Diseases, 302 Military Hospital of China - Peking University Teaching Hospital, Beijing, China
| | - Juan Li
- Department of Critical Care Medicine of Liver Disease, Beijing You'An Hospital, Capital Medical University, Beijing, China
| | - Juan Zhao
- Department of Critical Care Medicine of Liver Disease, Beijing You'An Hospital, Capital Medical University, Beijing, China
| | - Fu-Sheng Wang
- Department of Infectious Diseases, 302 Military Hospital of China - Peking University Teaching Hospital, Beijing, China
| | - Qing-Hua Meng
- Department of Critical Care Medicine of Liver Disease, Beijing You'An Hospital, Capital Medical University, Beijing, China
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Actualización en la insuficiencia hepática aguda sobre crónica. GASTROENTEROLOGIA Y HEPATOLOGIA 2018; 41:43-53. [DOI: 10.1016/j.gastrohep.2017.05.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Revised: 05/15/2017] [Accepted: 05/19/2017] [Indexed: 12/18/2022]
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Selva Rajoo A, Lim SG, Phyo WW, Tun T, Dan YY, Lee YM, Low HC, Lim K, Tan PS, Lee GH. Acute-on-chronic liver failure in a multi-ethnic Asian city: A comparison of patients identified by Asia-Pacific Association for the Study of the Liver and European Association for the Study of the Liver definitions. World J Hepatol 2017; 9:1133-1140. [PMID: 29075369 PMCID: PMC5643261 DOI: 10.4254/wjh.v9.i28.1133] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Revised: 07/23/2017] [Accepted: 09/14/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To explore the applicability of the Asia-Pacific Association for the Study of the Liver (APASL) and European Association for the Study of the Liver (EASL) guidelines for acute-on-chronic liver failure (ACLF) in profiling patients and determining the outcome.
METHODS Patients admitted to a tertiary hospital in Singapore with acute decompensation of liver disease from January 2004 to July 2014 are screened for ACLF according to the APASL and EASL criteria. The patients’ data (including basic demographics, information about existing chronic liver disease, information about the acute decompensation, relevant laboratory values during admission, treatment, and outcome) are retrospectively analyzed to determine the background, precipitating factors and outcome.
RESULTS A total of 458 liver patients is analyzed, and 78 patients with ACLF are identified. Sixty-three patients (80.8%) meet the APASL criteria, 64 patients (82.1%) meet the EASL criteria, and 49 patients (62.8%) fulfilled both criteria. The most common causes of acute liver injury are bacterial infections (59.0%), hepatitis B flare (29.5%), and variceal bleeding (24.4%). The common aetiologies of the underlying chronic disease included hepatitis B (43.6%), alcoholic (20.5%) and cryptogenic (11.5%) liver disease. The overall mortality rate is 61.5%. Increased age, the number of organ failures (as per CLIF-SOFA score), peak creatinine, INR, and amylase levels are associated with increased mortality or the need for liver transplantation. 14.3% of patients undergo liver transplantation with a 100% 1-year survival rate.
CONCLUSION Both APASL and EASL criteria have identified ACLF patients with high three-month mortality, but those who fulfill APASL criteria alone have a better survival.
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Affiliation(s)
- Anandraj Selva Rajoo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Seng-Gee Lim
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
- Institute of Molecular and Cell Biology, ASTAR, Singapore 138668, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
| | - Wah Wah Phyo
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
| | - Thandar Tun
- Department of Hepatology, Mandalay General Hospital, 30th St, Chan Aye Tharsan Township, Mandalay, Myanmar
| | - Yock-Young Dan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
| | - Yin-Mei Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
| | - How-Cheng Low
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
| | - Kieron Lim
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
| | - Poh-Seng Tan
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
| | - Guan-Huei Lee
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
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Gustot T, Agarwal B. Selected patients with acute-on-chronic liver failure grade 3 are not too sick to be considered for liver transplantation. J Hepatol 2017; 67:667-668. [PMID: 28923205 DOI: 10.1016/j.jhep.2017.07.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Revised: 07/21/2017] [Accepted: 07/21/2017] [Indexed: 02/07/2023]
Affiliation(s)
- Thierry Gustot
- Dept. Gastroenterology and Hepato-Pancreatology, C.U.B. Erasme Hospital, Brussels, Belgium; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium; Inserm Unité 1149, Centre de Recherche sur l'inflammation (CRI), Paris, France; UMR S_1149, Université Paris Diderot, Paris, France; The EASL-CLIF Consortium, European Foundation-CLIF, Barcelona, Spain.
| | - Banwari Agarwal
- Intensive Care Unit, Royal Free Hospital, London, UK; Institute for Liver and Digestive Health, University College London, Royal Free Campus, UK
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Choudhary NS, Saraf N, Saigal S, Soin AS. Liver Transplantation for Acute on Chronic Liver Failure. J Clin Exp Hepatol 2017; 7:247-252. [PMID: 28970712 PMCID: PMC5620362 DOI: 10.1016/j.jceh.2017.08.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Accepted: 08/16/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Acute-on chronic liver failure (ACLF) is defined as acute insult on previous liver disease that causes sudden worsening of liver functions. METHODS ACLF is characterized by high incidence of organ failure and prognosis is remarkably worse than patients with cirrhosis. Incidence of organ failures is very high despite best medical care and timely liver transplant before development of multi organ failure is associated with good survival rates. RESULTS At present, there are no reliable score or ways to correctly identify patients who are going to recover from patients who will need transplantation. Organ failures are important part of prognosis and to define need or futility of early liver transplantation. CONCLUSION Asian Pacific Association for the Study of the Liver (APASL) published their recommendations regarding ACLF in 2014. Several important studies regarding course/nature of disease and transplantation for ACLF became available after 2014 APASL recommendations and still there are some unanswered areas. The current review discusses various issues regarding liver transplantation in patients with ACLF.
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Affiliation(s)
| | - Neeraj Saraf
- Address for correspondence: Neeraj Saraf, Institute of Liver Transplantation and Regenerative Medicine, Medanta, The Medicity, Sector 38, Gurgaon, Haryana 122001, India.Institute of Liver Transplantation and Regenerative Medicine, Medanta, The MedicitySector 38GurgaonHaryana122001India
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Bernal W. Improving outcomes for transplantation of critically ill patients with cirrhosis? Clin Liver Dis (Hoboken) 2017; 10:25-28. [PMID: 30992754 PMCID: PMC6467230 DOI: 10.1002/cld.646] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Revised: 05/14/2017] [Accepted: 05/20/2017] [Indexed: 02/04/2023] Open
Affiliation(s)
- William Bernal
- Liver Intensive Therapy Unit, Institute of Liver StudiesKings College HospitalLondonUnited Kingdom
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Kok B, Ewasiuk A, Karvellas CJ. Liver transplant in acute-on-chronic liver failure: Evaluating the impact of organ dysfunction. Liver Int 2017; 37:651-652. [PMID: 28453923 DOI: 10.1111/liv.13365] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Affiliation(s)
- Beverley Kok
- Department of Critical Care Medicine, University of Alberta, Edmonton, AB, Canada
| | - Amanda Ewasiuk
- Department of Critical Care Medicine, University of Alberta, Edmonton, AB, Canada
| | - Constantine J Karvellas
- Department of Critical Care Medicine, University of Alberta, Edmonton, AB, Canada.,Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
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