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Rady ED, Anouti A, Mitchell MC, Cotter TG. Current Clinical Trials for Alcohol-Associated Hepatitis. THE AMERICAN JOURNAL OF PATHOLOGY 2025:S0002-9440(25)00116-6. [PMID: 40254132 DOI: 10.1016/j.ajpath.2025.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Revised: 03/22/2025] [Accepted: 03/28/2025] [Indexed: 04/22/2025]
Abstract
Alcohol-associated hepatitis (AH) is a severe form of alcohol-associated liver disease characterized by acute-onset jaundice and liver failure. AH carries a high mortality risk, particularly in severe cases. Although glucocorticoids have been the primary pharmacologic intervention for decades, their use is limited by a lack of long-term efficacy and significant side effects and relative contraindications. For patients who do not respond to glucocorticoids, early liver transplantation is a life-saving option; only a few patients qualify for this intervention, however. In recent years, advances in translational medicine have uncovered key mechanisms in AH pathophysiology, including microbiome interactions, proinflammatory signaling, and disruptions in hepatocyte function. These insights have led to the exploration of innovative pharmacologic treatments, targeting pathways such as the gut-liver axis, oxidative stress, inflammation, and liver regeneration. Despite promising results from ongoing clinical trials, several challenges persist, including low patient recruitment and retention rates, heterogeneity in trial design, and the lack of standardized endpoints. This review assesses the current pharmacologic landscape of AH, emphasizing emerging therapies and the ongoing challenges in AH clinical trials.
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Affiliation(s)
- Elias D Rady
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas
| | - Ahmad Anouti
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas
| | - Mack C Mitchell
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas
| | - Thomas G Cotter
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas.
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Yamazaki T, Schnabl B. Acute alcohol-associated hepatitis: Latest findings in non-invasive biomarkers and treatment. Liver Int 2025; 45:e15608. [PMID: 37183549 PMCID: PMC10646153 DOI: 10.1111/liv.15608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 04/15/2023] [Accepted: 05/03/2023] [Indexed: 05/16/2023]
Abstract
Acute alcohol-associated hepatitis (AH) is a syndrome that occurs in heavy and long-term drinkers and results in severe jaundice and liver failure. The mortality rate in severe cases is 20%-50% at 28 days, and in cases that do not improve despite appropriately timed corticosteroid therapy, the mortality rate reaches 70% at 6 months. The only curative treatment is early liver transplantation, but less than 2% of patients with severe AH are eligible. In order to improve the prognosis, diagnostic tools are needed to detect appropriate cases at risk of severe conditions, and new therapies need to be developed that can replace corticosteroids. Recent research has revealed that the pathogenesis of AH involves a complex of factors, including changes in the gut microbiota, inflammatory and cytokine signalling, oxidative stress and mitochondrial dysfunction, and abnormalities in the hepatic regenerative capacity. Non-invasive diagnostic tools focusing on these specific pathologies have been reported in recent years. In addition, several novel agents targeting specific pathways are currently being developed and tested in clinical trials. This review will provide an overview of alcohol-associated hepatitis and focus on the latest diagnostic tools, particularly non-invasive biomarkers, and novel therapies.
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Affiliation(s)
- Tomoo Yamazaki
- Department of Medicine, University of California San Diego, La Jolla, California, USA
- Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Nagano, Matsumoto, Japan
| | - Bernd Schnabl
- Department of Medicine, University of California San Diego, La Jolla, California, USA
- Department of Medicine, VA San Diego Healthcare System, California, San Diego, USA
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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Azoulay D, Desterke C, Bhangui P, Serrablo A, De Martin E, Cauchy F, Salloum C, Allard MA, Golse N, Vibert E, Sa Cunha A, Cherqui D, Adam R, Saliba F, Ichai P, Feray C, Scatton O, Lim C. Rescue Liver Transplantation for Posthepatectomy Liver Failure: A Systematic Review and Survey of an International Experience. Transplantation 2024; 108:947-957. [PMID: 37749790 DOI: 10.1097/tp.0000000000004813] [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: 09/27/2023]
Abstract
BACKGROUND Rescue liver transplantation (LT) is the only life-saving option for posthepatectomy liver failure (PHLF) whenever it is deemed as irreversible and likely to be fatal. The goals were to perform a qualitative systematic review of rescue LT for PHLF and a survey among various international LT experts. METHODS A literature search was performed from 2000 to 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Population, Intervention, Comparison, Outcome framework, and to this, the authors' experience was added. The international online open survey included 6 cases of PHLF extracted from the literature and submitted to 976 LT experts. The primary outcome was whether experts would consider rescue LT for each case. Interrater agreement among experts was calculated using the free-marginal multirater kappa methodology. RESULTS The review included 40 patients. Post-LT mortality occurred in 8 (20%) cases (7/28 with proven cancer and 1/12 with benign disease). In the long term, 6 of 21 (28.6%) survivors with cancer died of recurrence (median = 38 mo) and 15 (71.4%) were alive with no recurrence (median = 111 mo). All 11 survivors with benign disease were alive and well (median = 39 mo). In the international survey among experts in LT, the percentage agreement to consider rescue LT was 28%-98%, higher for benign than for malignant disease ( P = 0.011). Interrater agreement for the primary endpoint was low, expected 5-y survival >50% being the strongest independent predictor to consider LT. CONCLUSIONS Rescue LT for PHLF may achieve good results in selected patients. Considerable inconsistencies of decision-making exist among LT experts when considering LT for PHLF.
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Affiliation(s)
- Daniel Azoulay
- Centre Hépato-Biliaire, Hôpital Universitaire Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Christophe Desterke
- University of Medicine Paris Saclay, Le Kremlin-Bicêtre, France
- INSERM Unit UMR1310, Villejuif, France
| | - Prashant Bhangui
- Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Delhi NCR, India
| | - Alejandro Serrablo
- Department of Surgery, Miguel Servet University Hospital, Zaragoza, Spain
| | - Eleonora De Martin
- Centre Hépato-Biliaire, Hôpital Universitaire Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - François Cauchy
- Department of Hepato-biliary and Pancreatic Surgery and Liver Transplantation, University of Geneva, Geneva, Switzerland
| | - Chady Salloum
- Centre Hépato-Biliaire, Hôpital Universitaire Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Marc Antoine Allard
- Centre Hépato-Biliaire, Hôpital Universitaire Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Nicolas Golse
- Centre Hépato-Biliaire, Hôpital Universitaire Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Eric Vibert
- Centre Hépato-Biliaire, Hôpital Universitaire Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Antonio Sa Cunha
- Centre Hépato-Biliaire, Hôpital Universitaire Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Daniel Cherqui
- Centre Hépato-Biliaire, Hôpital Universitaire Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - René Adam
- Centre Hépato-Biliaire, Hôpital Universitaire Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Faouzi Saliba
- Centre Hépato-Biliaire, Hôpital Universitaire Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Philippe Ichai
- Centre Hépato-Biliaire, Hôpital Universitaire Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Cyrille Feray
- Centre Hépato-Biliaire, Hôpital Universitaire Paul Brousse, Université Paris-Saclay, Villejuif, France
| | - Olivier Scatton
- Département de Chirurgie et Transplantation Hépatique, Hôpital Universitaire Pitié-Salpêtrière, Sorbonne Université, Paris, France
- Centre de Recherche de Saint-Antoine (CRSA), INSERM, UMRS-938, Paris, France
| | - Chetana Lim
- Département de Chirurgie et Transplantation Hépatique, Hôpital Universitaire Pitié-Salpêtrière, Sorbonne Université, Paris, France
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Duan F, Liu C, Chang C, Song S, Zhai H, Cheng J, Yang S. Granulocyte colony-stimulating factor plus pentoxifylline increases short-term survival in patients with severe alcoholic hepatitis: a network meta-analysis. THE AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE 2024; 50:191-206. [PMID: 38011683 DOI: 10.1080/00952990.2023.2266117] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 09/28/2023] [Accepted: 09/28/2023] [Indexed: 11/29/2023]
Abstract
Background: Optimal treatments for severe alcoholic hepatitis (SAH) remain controversial. Previous network meta-analysis showed that corticosteroid (CS) combined with N-acetylcysteine (NAC) was superior in reducing short-term mortality of patients with SAH. Recently, granulocyte colony-stimulating factor (G-CSF) treatments for SAH yielded promising results.Objectives: To determine how currently available treatments affect the survival and complications of patients with SAH.Methods: The study was conducted following the guidelines of PRISMA. The data from PubMed, Embase, MEDLINE, Cochrane Library, and clinicaltrials.gov to October 2022 were searched, and patients with SAH with pharmacotherapy were included in our study. The primary outcome was short-term survival, and the other outcomes were medium- (3/6 months) or long-term (12 months) survival and complications after treatment. R software was used to establish network meta-analysis models and the result was expressed by the odd ratio (OR) value and 95% credible interval (Crls).Results: A total of 31 randomized controlled trials, including 19 treatment regimens, were enrolled in our study. As the primary outcome, G-CSF+ pentoxifylline (PTX) ranked first in one-month survival and showed significant superiority when compared with the placebo (OR 8.60, 95% Crls 1.92-45.10) and CS (OR 4.95, 95% Crls 1.11-25.53). Also, G-CSF+PTX ranked first in improving three-month survival and reducing the occurrence of infection. PTX+MTD ranked first in six-month survival, and G-CSF ranked first in twelve-month survival. CS+MTD ranked first in the occurrence of gastrointestinal bleeding and hepatorenal syndrome.Conclusions: The combination of G-CSF and PTX showed a significant benefit in improving the short-term survival of SAH patients.
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Affiliation(s)
- Fangfang Duan
- Division 3, Department of Hepatology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Chen Liu
- Division 3, Department of Hepatology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Chunyan Chang
- Division 3, Department of Hepatology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Shanshan Song
- Division 3, Department of Hepatology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hang Zhai
- Division 3, Department of Hepatology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Jun Cheng
- Division 3, Department of Hepatology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Song Yang
- Division 3, Department of Hepatology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Division 2, Department of Hepatology, The Fourth People's Hospital of Qinghai Province, Xining, China
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6
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Singal AK, Leggio L, DiMartini A. Alcohol use disorder in alcohol-associated liver disease: Two sides of the same coin. Liver Transpl 2024; 30:200-212. [PMID: 37934047 DOI: 10.1097/lvt.0000000000000296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 10/16/2023] [Indexed: 11/08/2023]
Abstract
Alcohol-associated liver disease (ALD) has emerged as the leading indication for liver transplantation (LT) worldwide, with 40% of LTs in the United States performed for ALD in 2019. The ALD-related health care burden accelerated during the COVID-19 pandemic, especially in young individuals. Alcohol use disorder (AUD), which focuses on the negative effects of alcohol on psychosocial, physical, and mental health, is present in the majority of patients with ALD, with moderate to severe AUD in 75%-80%. During the last decade, early liver transplantation (eLT) has emerged as a lifesaving treatment for selected patients with alcohol-associated hepatitis; these patients may have a higher risk of using alcohol after LT. The risk of alcohol use recurrence may be reduced during the pretransplant or post-transplant period with AUD treatment using behavioral and/or pharmacological therapies and with regular monitoring for alcohol use (self-reported and complemented with biomarkers like phosphatidylethanol). However, AUD treatment in patients with ALD is challenging due to patient, clinician, and system barriers. An integrated model to provide AUD and ALD care by hepatologists and addiction experts in a colocated clinic starting from LT evaluation and selection to monitoring listed candidates and then to following up on recipients of LT should be promoted. However, the integration of addiction and hepatology teams in an LT program in the real world is often present only during evaluation and candidate selection for LT. Data are emerging to show that a multidisciplinary integrated AUD treatment within an LT program reduces recurrent alcohol use after LT. If we want to continue using early liver transplantation for patients with severe alcohol-associated hepatitis, LT programs should focus on building integrated multidisciplinary care teams for the integrated treatment of both AUD and ALD.
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Affiliation(s)
- Ashwani K Singal
- Department of Medicine, University of South Dakota, Vermillion, South Dakota, USA
- Department of Gastroenterology and Hepatology, Avera McKennan University Hospital, Sioux Falls, South Dakota, USA
- Department of Transplant Hepatology, Avera Transplant Institute, Sioux Falls, South Dakota, USA
- Department of Medicine, VA Medical Center, Sioux Falls, South Dakota, USA
| | - Lorenzo Leggio
- Department of Neuropsychopharmacology Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, Division of Intramural Clinical and Biological Research, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
- Department of Behavioral and Social Sciences, Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island, USA
- Department of Medicine, Division of Addiction Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
- Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, USA
| | - Andrea DiMartini
- Departments of Psychiatry and Transplant Surgery, and the Clinical and Translational Science Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
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Shearer J, Johnson A, Masson S. Improving survival in alcohol-related hepatitis: what's new? Frontline Gastroenterol 2024; 15:42-49. [PMID: 38487555 PMCID: PMC10935532 DOI: 10.1136/flgastro-2022-102362] [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: 04/24/2023] [Accepted: 06/21/2023] [Indexed: 03/17/2024] Open
Abstract
Alcohol-related hepatitis (AH) is the most florid presentation of alcohol-related liver disease and carries a high short-term and long-term mortality rate. Specific treatment options remain inadequate. The current management approach for AH focuses on early identification, careful screening and treatment of infection, as well as identification of those patients who may benefit from corticosteroid therapy based on validated prognostic scoring systems. In recent years, there has been growing interest in exploring novel therapies for AH, which may offer alternative treatment options beyond the traditional approaches. Additionally, early liver transplantation (LT) has emerged as a promising option in selected cases with growing evidence supporting its role. In this review, we will discuss the current evidence base for the assessment and treatment of AH, and how these advances are shaping practice to improve outcomes in the UK.
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Affiliation(s)
- Jessica Shearer
- Liver Unit, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Amy Johnson
- Liver Unit, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Steven Masson
- Liver Unit, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
- Translational and Clinical Research Institute, Newcastle University Faculty of Medical Sciences, Newcastle upon Tyne, UK
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Jophlin LL, Singal AK, Bataller R, Wong RJ, Sauer BG, Terrault NA, Shah VH. ACG Clinical Guideline: Alcohol-Associated Liver Disease. Am J Gastroenterol 2024; 119:30-54. [PMID: 38174913 PMCID: PMC11040545 DOI: 10.14309/ajg.0000000000002572] [Citation(s) in RCA: 70] [Impact Index Per Article: 70.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 10/04/2023] [Indexed: 01/05/2024]
Abstract
ABSTRACT Alcohol-associated liver disease (ALD) is the most common cause of advanced hepatic disease and frequent indication for liver transplantation worldwide. With harmful alcohol use as the primary risk factor, increasing alcohol use over the past decade has resulted in rapid growth of the ALD-related healthcare burden. The spectrum of ALD ranges from early asymptomatic liver injury to advanced disease with decompensation and portal hypertension. Compared with those with other etiologies of liver disease, patients with ALD progress faster and more often present at an advanced stage. A unique phenotype of advanced disease is alcohol-associated hepatitis (AH) presenting with rapid onset or worsening of jaundice, and acute on chronic liver failure in severe forms conveying a 1-month mortality risk of 20%-50%. The model for end stage disease score is the most accurate score to stratify AH severity (>20 defined as severe disease). Corticosteroids are currently the only available therapeutic with proven efficacy for patients with severe AH, providing survival benefit at 1 month in 50%-60% of patients. Abstinence of alcohol use, a crucial determinant of long-term outcomes, is challenging to achieve in ALD patients with concurrent alcohol use disorder (AUD). As patients with ALD are rarely treated for AUD, strategies are needed to overcome barriers to AUD treatment in patients with ALD and to promote a multidisciplinary integrated care model with hepatology, addiction medicine providers, and social workers to comprehensively manage the dual pathologies of liver disease and of AUD. Liver transplantation, a definitive treatment option in patients with advanced cirrhosis, should be considered in selected patients with AH, who are unresponsive to medical therapy and have a low risk of relapse to posttransplant alcohol use. Level of evidence and strength of recommendations were evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations system. This guideline was developed under the American College of Gastroenterology Practice Parameters Committee.
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Affiliation(s)
- Loretta L. Jophlin
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville Health, Louisville, Kentucky, USA
| | - Ashwani K. Singal
- Division of Gastroenterology and Hepatology, University of South Dakota, Sioux Falls, South Dakota, USA
| | - Ramon Bataller
- Liver Unit, Department of Digestive and Metabolic Diseases, Hospital Clinic, Barcelona, Spain
| | - Robert J. Wong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA
| | - Bryan G. Sauer
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA
| | - Norah A. Terrault
- Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, California, USA
| | - Vijay H. Shah
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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9
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Murakami S, Imamura M, Uchida T, Suehiro Y, Namba M, Fujii Y, Uchikawa S, Teraoka Y, Fujino H, Ono A, Nakahara T, Murakami E, Okamoto W, Yamauchi M, Kawaoka T, Miki D, Hayes NC, Tsuge M, Aikata H, Ohira M, Ohdan H, Oka S. Serum interleukin-6 level predicts the prognosis for patients with alcohol-related acute-on-chronic liver failure. Hepatol Int 2023; 17:1225-1232. [PMID: 37101102 DOI: 10.1007/s12072-023-10532-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 04/01/2023] [Indexed: 04/28/2023]
Abstract
AIM Heavy alcohol consumption is the most common etiology of acute-on-chronic liver failure (ACLF) in Japan. In some patients, ACLF is associated with a fatal outcome in less than 6 months. We evaluated the prognosis of patients with alcohol-related ACLF in our cohort and explored the prognostic factors. METHODS Forty-six patients with alcoholic liver cirrhosis who fulfilled the Japanese diagnostic criteria for ACLF, including those classified as extended and/or probable, were enrolled in this study. Serum concentrations of inflammatory cytokines (interleukin [IL]-1β, IL-6, IL-8, IL-10, IL-12p70 and TNFα) were measured. We assessed prognosis and identified factors associated with survival. RESULTS During the median 33-day observation period, 19 patients died, and 3 patients underwent living donor liver transplantation. Cumulative survival rates of patients treated without liver transplantation were 69, 48, 41, and 36% at 1, 3, 6, and 12 months, respectively. Eighteen of the 19 deceased patients died within 6 months after ACLF diagnosis. Serum concentrations of inflammatory cytokines were significantly elevated, and patients who underwent liver transplantation or who died within 6 months after admission had significantly higher serum IL-6 levels than the survival group. Multivariate analysis identified IL-6 > 23.3 pg/mL at admission and model for end-stage liver disease (MELD) score ≥ 25 on day 4 of admission as significant independent factors for mortality within 6 months. CONCLUSION Serum IL-6 level and Day-4 MELD were prognostic factors for alcohol-related ACLF. Early liver transplantation is a potential treatment option for patients whose prognosis is expected to be poor.
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Affiliation(s)
- Serami Murakami
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Michio Imamura
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan.
| | - Takuro Uchida
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Yosuke Suehiro
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Maiko Namba
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Yasutoshi Fujii
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Shinsuke Uchikawa
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Yuji Teraoka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Hatsue Fujino
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Atsushi Ono
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Takashi Nakahara
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Eisuke Murakami
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Wataru Okamoto
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
- Cancer Treatment Center, Hiroshima University Hospital, Hiroshima, Japan
| | - Masami Yamauchi
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Daiki Miki
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Nelson C Hayes
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Masataka Tsuge
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
- Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
| | - Masahiro Ohira
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
- Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shiro Oka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan
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10
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Madigan S, Tashkent Y, Trehan S, Muller K, Wigg A, Woodman R, Ramachandran J. Acute on chronic liver failure: A South Australian experience. JGH Open 2023; 7:717-723. [PMID: 37908287 PMCID: PMC10615173 DOI: 10.1002/jgh3.12974] [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: 11/18/2022] [Revised: 04/21/2023] [Accepted: 09/08/2023] [Indexed: 11/02/2023]
Abstract
Background and Aim Acute on chronic liver failure (ACLF) is a clinical syndrome described in patients with acute decompensation (AD) of cirrhosis, characterized by organ failures and high mortality. Intensive management, including liver transplantation (LT), has been shown to improve survival. To address the limited Australian data on ACLF, we describe the prevalence, clinical profile, and outcome of ACLF in an Australian cohort of hospitalized patients. Methods A retrospective review of hepatology admissions in a tertiary hospital from 1 January 2017 to 31 December 2019 identified AD and ACLF cohorts, as defined by the European Association for Study of the Liver definition. Patient characteristics, clinical course, survival at 28- and 90-day survival, and feasibility of LT were analyzed. Results Among the 192 admissions with AD, 74 admissions (39%) met ACLF criteria. A prior diagnosis of alcohol-related cirrhosis was highly prevalent in both cohorts. Grade-1 ACLF was the most frequent (60%), with renal failure being the commonest organ failure; 28-day (23% vs 2%, P = <0.001) and 90-day mortality (36% vs 16%, P = 0.002) were higher in ACLF than AD. Due to ongoing alcohol use disorder (AUD), only six patients underwent LT assessment during ACLF admission. Conclusion ACLF was common in our cohort of cirrhosis with AD and was associated with high mortality. AUD despite prior cirrhosis diagnosis was a barrier to LT. Prioritization of ACLF patients for LT after addressing AUD and relaxation of the 6-month abstinence rule may improve ACLF survival and should be addressed in prospective studies.
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Affiliation(s)
- Shauna Madigan
- Department of Gastroenterology and HepatologyFlinders Medical CentreBedford ParkSouth AustraliaAustralia
- College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
| | - Yasmina Tashkent
- Department of Gastroenterology and HepatologyFlinders Medical CentreBedford ParkSouth AustraliaAustralia
- College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
| | - Sharad Trehan
- Department of General MedicineFlinders Medical CentreBedford ParkSouth AustraliaAustralia
| | - Kate Muller
- Department of Gastroenterology and HepatologyFlinders Medical CentreBedford ParkSouth AustraliaAustralia
- College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
| | - Alan Wigg
- Department of Gastroenterology and HepatologyFlinders Medical CentreBedford ParkSouth AustraliaAustralia
- College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
| | - Richard Woodman
- College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
| | - Jeyamani Ramachandran
- Department of Gastroenterology and HepatologyFlinders Medical CentreBedford ParkSouth AustraliaAustralia
- College of Medicine and Public HealthFlinders UniversityBedford ParkSouth AustraliaAustralia
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11
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Yilma M, Dalal N, Wadhwani SI, Hirose R, Mehta N. Geographic disparities in access to liver transplantation. Liver Transpl 2023; 29:987-997. [PMID: 37232214 PMCID: PMC10914246 DOI: 10.1097/lvt.0000000000000182] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 04/08/2023] [Indexed: 05/27/2023]
Abstract
Since the Final Rule regarding transplantation was published in 1999, organ distribution policies have been implemented to reduce geographic disparity. While a recent change in liver allocation, termed acuity circles, eliminated the donor service area as a unit of distribution to decrease the geographic disparity of waitlisted patients to liver transplantation, recently published results highlight the complexity of addressing geographic disparity. From geographic variation in donor supply, as well as liver disease burden and differing model for end-stage liver disease (MELD) scores of candidates and MELD scores necessary to receive liver transplantation, to the urban-rural disparity in specialty care access, and to neighborhood deprivation (community measure of socioeconomic status) in liver transplant access, addressing disparities of access will require a multipronged approach at the patient, transplant center, and national level. Herein, we review the current knowledge of these disparities-from variation in larger (regional) to smaller (census tract or zip code) levels to the common etiologies of liver disease, which are particularly affected by these geographic boundaries. The geographic disparity in liver transplant access must balance the limited organ supply with the growing demand. We must identify patient-level factors that contribute to their geographic disparity and incorporate these findings at the transplant center level to develop targeted interventions. We must simultaneously work at the national level to standardize and share patient data (including socioeconomic status and geographic social deprivation indices) to better understand the factors that contribute to the geographic disparity. The complex interplay between organ distribution policy, referral patterns, and variable waitlisting practices with the proportion of high MELD patients and differences in potential donor supply must all be considered to create a national policy strategy to address the inequities in the system.
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Affiliation(s)
- Mignote Yilma
- Department of Surgery, University of California San Francisco
- National Clinician Scholars Program, University of California San Francisco
| | - Nicole Dalal
- Department of Medicine, University of California San Francisco
| | | | - Ryutaro Hirose
- Department of Transplant, University of California San Francisco
| | - Neil Mehta
- Department of Medicine, University of California San Francisco
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12
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Mitchell J, Herrick-Reynolds K, Motter JD, Teles M, Kates O, Sung H, Chen PH, King E, Cameron A. Transplant Center Attitudes Toward Early Liver Transplant for Alcohol-associated Liver Disease. Transplant Direct 2023; 9:e1532. [PMID: 37649789 PMCID: PMC10465102 DOI: 10.1097/txd.0000000000001532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 06/29/2023] [Accepted: 07/14/2023] [Indexed: 09/01/2023] Open
Abstract
Background Many centers have removed 6-mo pretransplant alcohol abstinence requirements to provide early liver transplant (ELT) for individuals with severe alcohol-associated liver disease (ALD), but the practice remains controversial. Using data collected from a nationally distributed survey, this study examines the practices and attitudes of transplant centers in the United States regarding ELT. Methods A 20-item survey designed to assess center practices and provider attitudes was distributed to 225 medical and surgical directors from 143 liver transplant centers via email. Results Surveys were completed by 28.9% (n = 65) of directors and 39% (n = 56) of transplant centers. All responding centers reported evaluating patients for ELT. Circumstances for considering ELT included <6 mo of survival without a transplant (96.4%) and inability to participate in alcohol addiction therapy pretransplant (75%). Most (66%) directors indicated their center had established criteria for listing candidates with severe ALD for ELT. Regarding important factors for ELT candidate listing, 57.1% indicated patient survival, 37.5% indicated graft survival, and 55.4% indicated having a low risk of relapse. Only 12.7% of directors affirmed the statement, "Six months of pretransplant abstinence decreases the risk of relapse." Conclusions More centers are providing ELT for severe ALD. Inability to participate in alcohol addiction therapy and <6 mo of survival are commonly reported circumstances for considering ELT. Continued investigation of posttransplant outcomes in patients receiving ELT is essential to establishing a national consensus for distributing this valuable resource.
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Affiliation(s)
- Jonathan Mitchell
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | | | - Jennifer D. Motter
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Mayan Teles
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Olivia Kates
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Hannah Sung
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Po-Hung Chen
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Elizabeth King
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Andrew Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
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13
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Thakral N, Deutsch-Link S, Singal AK. Therapeutic Pipeline in Alcohol-Associated Liver Disease. Semin Liver Dis 2023; 43:60-76. [PMID: 36572032 PMCID: PMC11503467 DOI: 10.1055/s-0042-1759614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Alcohol-associated liver disease is a leading cause of mortality and morbidity worldwide. Patients with alcohol-associated liver disease are often diagnosed at advanced stage and disease spectrum including alcoholic hepatitis, a severe manifestation with a high short-term mortality. Corticosteroid, recommended first-line treatment for patients with alcoholic hepatitis, is a very suboptimal treatment. Although the use of early liver transplantation has increased with consistent benefit in select patients with alcoholic hepatitis, its use remains heterogeneous worldwide due to lack of uniform selection criteria. Over the last decade, several therapeutic targets have evolved of promise with ongoing clinical trials in patients with cirrhosis and alcoholic hepatitis. Even with availability of effective medical therapies for alcohol-associated liver disease, long-term outcome depends on abstinence from alcohol use in any spectrum of alcohol-associated liver disease. However, alcohol use disorder treatment remains underutilized due to several barriers even in patients with advanced disease. There is an urgent unmet need to implement and promote integrated multidisciplinary care model with hepatologists and addiction experts to provide comprehensive management for these patients. In this review, we will discuss newer therapies targeting liver disease and therapies targeting alcohol use disorder in patients with alcohol-associated liver disease.
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Affiliation(s)
- Nimish Thakral
- Division of Gastroenterology and Hepatology, University of Kentucky, Lexington, Kentucky
| | - Sasha Deutsch-Link
- Department of Medicine, University of North Carolina at Chapel Hill, North Carolina
| | - Ashwani K. Singal
- Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, South Dakota
- Division of Transplant Hepatology, Avera Transplant Institute, Sioux Falls, South Dakota
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14
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Alcoholic Hepatitis. Med Clin North Am 2023; 107:533-554. [PMID: 37001952 DOI: 10.1016/j.mcna.2022.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Abstract
Alcoholic hepatitis (AH) is a unique clinical syndrome on the spectrum of alcohol-associated liver disease (ALD). It constitutes a rising epidemic with increasing incidence and major public health implications. In severe AH, 30-day mortality approaches 30%, yet therapeutic options remain limited. Survival benefit from corticosteroids, the mainstay of medical treatment, is short-lived. Among corticosteroid nonresponders, the use of early liver transplantation is heterogeneous across centers and remains limited by significant barriers. Long-term prognosis is largely dictated by abstinence; however, comorbid alcohol use disorder remains undertreated. Efforts to address these challenges are required to curb the AH epidemic.
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15
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Wakil A, Niazi M, Meybodi MA, Pyrsopoulos NT. Emerging Pharmacotherapies in Alcohol-Associated Hepatitis. J Clin Exp Hepatol 2023; 13:116-126. [PMID: 36647403 PMCID: PMC9840076 DOI: 10.1016/j.jceh.2022.06.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 06/25/2022] [Indexed: 02/07/2023] Open
Abstract
UNLABELLED The incidence of alcoholic-associated hepatitis (AH) is increasing. The treatment options for severe AH (sAH) are scarce and limited to corticosteroid therapy which showed limited mortality benefit in short-term use only. Therefore, there is a dire need for developing safe and effective therapies for patients with sAH and to improve their high mortality rates.This review article focuses on the current novel therapeutics targeting various mechanisms in the pathogenesis of alcohol-related hepatitis. Anti-inflammatory agents such as IL-1 inhibitor, Pan-caspase inhibitor, Apoptosis signal-regulating kinase-1, and CCL2 inhibitors are under investigation. Other group of agents include gut-liver axis modulators, hepatic regeneration, antioxidants, and Epigenic modulators. We describe the ongoing clinical trials of some of the new agents for alcohol-related hepatitis. CONCLUSION A combination of therapies was investigated, possibly providing a synergistic effect of drugs with different mechanisms. Multiple clinical trials of novel therapies in AH remain ongoing. Their result could potentially make a difference in the clinical course of the disease. DUR-928 and granulocyte colony-stimulating factor had promising results and further trials are ongoing to evaluate their efficacy in the large patient sample.
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Key Words
- AH, alcohol-Associated hepatitis
- ALD, Alcohol-associated liver disease
- ASK-1, Apoptosis signal-regulating kinase-1
- AUD, alcohol use disorder
- CCL2, C–C chemokine ligand type 2
- CVC, Cenicriviroc
- ELAD, Extracorporeal liver assist device
- FMT, Fecal Microbiota Transplant
- G-CSF, Granulocyte colony-stimulating factor
- HA35, Hyaluronic Acid 35KD
- IL-1, interleukin 1
- IL-6, interleukin 6
- LCFA, saturated long-chain fatty acids
- LDL, low-density lipoprotein cholesterol
- LPS, Lipopolysaccharides
- MCP-1, monocyte chemoattractant protein −1
- MDF, Maddrey's discriminant function
- MELD, Model for end-stage disease
- NAC, N-acetylcysteine
- NLRs, nucleotide-binding oligomerization domain-like receptors
- PAMPs, Pathogen-associated molecular patterns
- RCT, Randomized controlled trial
- SAM, S-Adenosyl methionine
- SCFA, short-chain fatty acids. 5
- TLRs, Toll-like receptors
- TNF, tumor necrotic factor
- alcohol-associated hepatitis
- anti-inflammatory
- antioxidants
- liver-gut axis
- microbiome
- sAH, severe alcohol-associated hepatitis
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Affiliation(s)
- Ali Wakil
- Department of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, New York, New Jersey, USA
| | - Mumtaz Niazi
- Department of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, New York, New Jersey, USA
| | - Mohamad A. Meybodi
- Department of Internal Medicine, Rutgers New Jersey Medical School, New York, New Jersey, USA
| | - Nikolaos T. Pyrsopoulos
- Department of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, New York, New Jersey, USA
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16
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Sedki M, Ahmed A, Goel A. Ethical and allocation issues in liver transplant candidates with alcohol related liver disease. Transl Gastroenterol Hepatol 2022; 7:26. [PMID: 35892052 PMCID: PMC9257533 DOI: 10.21037/tgh-2020-13] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 09/17/2020] [Indexed: 09/01/2024] Open
Abstract
In the past decade, alcohol-related liver disease (ALD) has become the leading indication for liver transplantation (LT) in the United States. Despite this major development, there still remains some controversy in a distinct subset of this patient population, those presenting with alcoholic hepatitis (AH). There is significant debate within the transplant community regarding acceptance criteria for patients with AH requiring LT, especially those with less than 6 months of sobriety. With that being said, LT in the setting of ALD and AH has shown an improvement in survival rates; additionally, many studies have reported that careful selection of patients with ALD has produced excellent post-transplant outcomes even if transplant occurred with less than 6 months of sobriety. In this review, we aim to discuss the ethical and allocation-associated issues that arise when considering ALD and/or AH for LT; furthermore, we delve into the history, controversies, current guidelines, and future directions of LT in this subgroup.
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Affiliation(s)
- Mai Sedki
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Aparna Goel
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
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17
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Cabezas J. Management of Alcohol-Related Liver Disease and Its Complications. Clin Drug Investig 2022; 42:47-53. [PMID: 35467296 PMCID: PMC9205805 DOI: 10.1007/s40261-022-01143-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/16/2022] [Indexed: 12/19/2022]
Abstract
Alcohol-related liver disease (ALD) is a major healthcare/economic burden and one of the leading causes of liver transplantation. New epidemiological studies that detail the course of the disease are needed since, despite its high prevalence, it is still a stigmatised condition with underlying pathology. Alcoholic hepatitis, as the highest expression of ALD, has high morbidity. Current treatments have suboptimal results with the exception of liver transplantation. Epidemiological studies must also be developed to improve prevention and implement early diagnosis policies. It is essential to develop multidisciplinary health models that allow the liver transplantation candidate to be approached in a holistic way, both for indication and follow up. The implementation of alcohol consumption biomarkers (ethyl glucuronide, phosphatidylethanol) can assist in diagnosing and supporting recovery. There are several initiatives with new therapies that must be validated to establish their effectiveness and indication.
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Affiliation(s)
- Joaquín Cabezas
- Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, Clinical and Translational Research in Digestive Diseases Group-IDIVAL, Santander, Cantabria, Spain.
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18
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Jakhete N, Abutaleb A, Shetty K. Transplant in acute alcoholic hepatitis: a relative contraindication. Curr Opin Organ Transplant 2022; 27:93-97. [PMID: 35166269 DOI: 10.1097/mot.0000000000000974] [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: 11/03/2022]
Abstract
PURPOSE OF REVIEW The aim of this review is to provide a critical analysis of liver transplantation for alcoholic hepatitis, with an emphasis on barriers to long-term success in current implementation strategies across the United States. RECENT FINDINGS Alcohol-associated liver disease is the most rapidly increasing indication for liver transplantation in the USA. Its most severe form, acute alcoholic hepatitis, has a rising incidence particularly in the young, and is associated with a high mortality risk. Although excellent outcomes following liver transplantation for alcoholic hepatitis can be achieved, several barriers limit its routine use. These constraints include risk of allograft dysfunction, the recognition of alcohol use disorder as a multisystem disease and ethical considerations. SUMMARY Although liver transplantation is an important option in a carefully selected group of candidates, it should not be considered the standard of care in this condition. Consistency, transparency and consensus are necessary to formulate and implement policy changes at the national level. Following liver transplantation, wraparound services are important for relapse prevention, and to ensure long-term success and survival in this challenging group of patients.
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Affiliation(s)
- Neha Jakhete
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
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19
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Germani G, Angrisani D, Addolorato G, Merli M, Mazzarelli C, Tarli C, Lattanzi B, Panariello A, Prandoni P, Craxì L, Forza G, Feltrin A, Ronzan A, Feltracco P, Grieco A, Agnes S, Gasbarrini A, Rossi M, De Carlis L, Francesco D, Cillo U, Belli LS, Burra P. Liver transplantation for severe alcoholic hepatitis: A multicenter Italian study. Am J Transplant 2022; 22:1191-1200. [PMID: 34954874 DOI: 10.1111/ajt.16936] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 12/14/2021] [Accepted: 12/14/2021] [Indexed: 01/25/2023]
Abstract
There is increasing evidence that early liver transplantation (eLT), performed within standardized protocols can improve survival in severe alcoholic hepatitis (sAH). The aim of the study was to assess outcomes after eLT for sAH in four Italian LT centers and to compare them with non-responders to medical therapy excluded from eLT. Patients admitted for sAH (2013-2019), according to NIAAA criteria, were included. Patients not responding to medical therapy were placed on the waiting list for eLT after a strict selection. Histological features of explanted livers were evaluated. Posttransplant survival and alcohol relapse were evaluated. Ninety-three patients with severe AH were evaluated (65.6% male, median [IQR] age: 47 [42-56] years). Forty-five of 93 patients received corticosteroids, 52 of 93 were non-responders and among these, 20 patients were waitlisted. Sixteen patients underwent LT. Overall, 6-, 12-, and 24-month survival rates were 100% significantly higher compared with non-responders to medical therapy who were denied LT (45%, 45%, and 36%; p < .001). 2/16 patients resumed alcohol intake, one at 164 days and one at 184 days. Early LT significantly improves survival in sAH non-responding to medical therapy, when a strict selection process is applied. Further studies are needed to properly assess alcohol relapse rates.
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Affiliation(s)
- Giacomo Germani
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Debora Angrisani
- Department of Hepatology and Gastroenterology, ASST GOM Niguarda Hospital, Milan, Italy
| | - Giovanni Addolorato
- Alcohol Use Disorders Unit, Department of Internal Medicine, Institute of Internal Medicine, Gemelli Hospital, Catholic University of Rome, Rome, Italy.,Internal Medicine, Gastroenterology and Hepatology Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Manuela Merli
- Gastroenterology, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Chiara Mazzarelli
- Department of Hepatology and Gastroenterology, ASST GOM Niguarda Hospital, Milan, Italy
| | - Claudia Tarli
- Alcohol Use Disorders Unit, Department of Internal Medicine, Institute of Internal Medicine, Gemelli Hospital, Catholic University of Rome, Rome, Italy
| | - Barbara Lattanzi
- Gastroenterology, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Adelaide Panariello
- Department of Mental Health and Addiction Services, Niguarda Hospital, Milan, Italy
| | - Paola Prandoni
- Department of Mental Health and Addiction Services, Niguarda Hospital, Milan, Italy
| | - Lucia Craxì
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, Palermo, Italy
| | - Giovanni Forza
- Department of Legal and Occupational Medicine, Toxicology and Public Health, Padua University Hospital, Padua, Italy
| | | | - Andrea Ronzan
- Psychiatry Unit, Padua University Hospital, Padua, Italy
| | - Paolo Feltracco
- Anesthesia and Intensive Care, Department of Medicine, Padua University Hospital, Padua, Italy
| | - Antonio Grieco
- Liver Transplant Medicine Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Salvatore Agnes
- General Surgery and Liver Transplant Unit, Università Cattolica - Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy
| | - Antonio Gasbarrini
- Internal Medicine, Gastroenterology and Hepatology Unit, Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Massimo Rossi
- General Surgery and Organ Transplantation Unit, Department of General 3 Surgery and Organ Transplantation, Sapienza University of Rome, Rome, Italy
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy.,School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - D'Amico Francesco
- Hepatobiliary Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Luca S Belli
- Department of Hepatology and Gastroenterology, ASST GOM Niguarda Hospital, Milan, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
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DiMartini AF, Leggio L, Singal AK. Barriers to the management of alcohol use disorder and alcohol-associated liver disease: strategies to implement integrated care models. Lancet Gastroenterol Hepatol 2022; 7:186-195. [DOI: 10.1016/s2468-1253(21)00191-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 05/20/2021] [Accepted: 05/25/2021] [Indexed: 02/07/2023]
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21
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Zhang BH, Cai YS, Yang JY. Liver Transplant for Alcohol-Associated Liver Disease. JAMA Surg 2022; 157:360. [PMID: 34985523 DOI: 10.1001/jamasurg.2021.6550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- Bo-Han Zhang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Yun-Shi Cai
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Jia-Yin Yang
- Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China
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22
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Integration of addiction treatment and behavioral therapies in comprehensive liver transplantation care to augment adherence and reduce alcohol relapse. JOURNAL OF LIVER TRANSPLANTATION 2022. [DOI: 10.1016/j.liver.2021.100061] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
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23
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Management of alcohol use disorder in patients with cirrhosis in the setting of liver transplantation. Nat Rev Gastroenterol Hepatol 2022; 19:45-59. [PMID: 34725498 PMCID: PMC8559139 DOI: 10.1038/s41575-021-00527-0] [Citation(s) in RCA: 77] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/21/2021] [Indexed: 02/07/2023]
Abstract
The prevalence of alcohol use disorder (AUD) has been steadily increasing over the past decade. In parallel, alcohol-associated liver disease (ALD) has been increasing at an alarming rate, especially among young patients. Data suggest that most patients with ALD do not receive AUD therapy. Although liver transplantation is the only curative therapy for end-stage ALD, transplant candidacy is often a matter of debate given concerns about patients being under-treated for AUD and fears of post-transplantation relapse affecting the allograft. In this Review, we discuss diagnosis, predictors and effects of relapse, behavioural therapies and pharmacotherapies, and we also propose an integrative, multidisciplinary and multimodality approach for treating AUD in patients with cirrhosis, especially in the setting of liver transplantation. Notably, this approach takes into account the utility of AUD pharmacotherapy in patients on immunosuppressive medications and those with renal impairment after liver transplantation. We also propose a comprehensive and objective definition of relapse utilizing contemporary biomarkers to guide future clinical trials. Future research using the proposed approach and definition is warranted with the goal of optimizing AUD treatment in patients with cirrhosis, the transplant selection process and post-transplantation care of patients with AUD.
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Choi G, Benhammou JN, Yum JJ, Saab EG, Patel AP, Baird AJ, Aguirre S, Farmer DG, Saab S. Barriers for Liver Transplant in Patients with Alcohol-Related Hepatitis. J Clin Exp Hepatol 2022; 12:13-19. [PMID: 35068780 PMCID: PMC8766699 DOI: 10.1016/j.jceh.2021.09.015] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 09/13/2021] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Liver transplantation (LT) for alcohol-related liver disease has historically been reserved for patients who have been six months abstinent. Given the increasing incidence of alcohol-related hepatitis (AH) and dismal survival in patients who fail medical therapy, transplant centers are extending their acceptance criteria for patients with less than 6 months of sobriety. We sought to determine the barriers for listing. METHODS We conducted a retrospective chart review of all inpatient LT referrals for a diagnosis of AH between September 2019 and December 2020. LT evaluations were performed by a multidisciplinary team. Descriptive statistics were reported using mean and standard deviation (SD) or percentage where appropriate. RESULTS During our study period, 82 patients were evaluated for LT. Of these 82 patients, 62 were declined for liver transplantation. The mean (SD) age of the 62-patient cohort was 44 years (10.7), and most patients were men. The mean (SD) number of reasons for denial was 2 (0.97). Four patients had medical contraindications for transplant. Twenty-seven (44%) and 35 (56%) patients lacked insight and were at risk of alcohol relapse, respectively. Forty-three (69%) and fourteen (22.5%) patients had insufficient social support and an inability to maintain a therapeutic relationship with the transplant team, respectively. CONCLUSION Patients are more likely denied for psychosocial factors than medical comorbidities. The majority were due to lack of insight, insufficient social support, and inability to maintain a therapeutic relationship with the transplant team. Resources should be allocated to address these issues.
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Affiliation(s)
- Gina Choi
- Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
- Department of Surgery, University of California, Los Angeles, Los Angeles, CA, USA
| | - Jihane N. Benhammou
- Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - Jung J. Yum
- Department of Surgery, University of California, Los Angeles, Los Angeles, CA, USA
| | - Elena G. Saab
- Department of Surgery, University of California, Los Angeles, Los Angeles, CA, USA
| | - Ankur P. Patel
- Department of Surgery, University of California, Los Angeles, Los Angeles, CA, USA
| | - Andrew J. Baird
- Department of Nursing, University of California, Los Angeles, Los Angeles, CA, USA
| | - Stephanie Aguirre
- Department of Social Work, University of California, Los Angeles, Los Angeles, CA, USA
| | - Douglas G. Farmer
- Department of Surgery, University of California, Los Angeles, Los Angeles, CA, USA
| | - Sammy Saab
- Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
- Department of Surgery, University of California, Los Angeles, Los Angeles, CA, USA
- Department of Nursing, University of California, Los Angeles, Los Angeles, CA, USA
- Address for correspondence. Sammy Saab, MD, MPH, AGAF, FAASLD, Pfleger Liver Institute, UCLA Medical Center, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095, USA. Tel.: +1 310 206 6705; fax: +1 310 206 4197.
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25
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Elfeki MA, Singal AK. Early Liver Transplantation: An Evolving Therapeutic Option for Alcohol-Associated Liver Disease. J Clin Exp Hepatol 2022; 12:3-5. [PMID: 35068777 PMCID: PMC8766704 DOI: 10.1016/j.jceh.2021.10.144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 10/22/2021] [Indexed: 01/03/2023] Open
Affiliation(s)
- Mohamed A. Elfeki
- Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD, USA
- Division of Transplant Hepatology, Avera Transplant Institute, Sioux Falls, SD, USA
| | - Ashwani K. Singal
- Address for correspondence. Ashwani K. Singal, Professor of Medicine and Director Hepatology Elective, University of South Dakota Sanford School of Medicine, Transplant Hepatologist and Chief Clinical Research Affairs, Avera McKennan University Hospital and Transplant Institute, Sioux Falls, SD 57105, USA. Tel.: +605-322-8535.
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26
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Caputo F, Testino G. Orthotopic liver transplantation for patients with end-stage alcohol-related liver disease and severe acute alcohol-related hepatitis. Minerva Surg 2021; 76:444-449. [PMID: 33433074 DOI: 10.23736/s2724-5691.20.08685-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Worldwide, cirrhosis due to alcohol-related liver disease (ALD) is responsible for 0.9% of global deaths and 47.9% of cirrhosis-related deaths. End-stage ALD (ESALD) is the final condition of alcohol-related cirrhosis, and severe acute alcohol-related hepatitis (SAAH) is a distinct clinical syndrome associated with the consumption of large amounts of alcohol. In some cases, ESALD, and SAAH may need liver transplantation (LT). The severity of ESALD can improve after a few months (three months) of abstinence from alcohol, avoiding or delaying the need for LT. Conversely, patients with ESALD with a poor prognosis (MELD≥15) may be candidates for LT after three months of abstinence; in these patients, the 6 months rule needs to be revised. In addition, in non-responders to steroid therapy, the indication for early LT in patients with SAAH and acute on chronic liver failure (ACLF) due to alcohol use find indication in carefully selected patients (those with good insight into their alcohol problems and good social support). Thus, the role of a multi-disciplinary team of experts in the management of alcohol use disorder, ESALD and SAAH working in the same institution, the support of the patient's family and self-help groups represent a crucial approach in the reinforcement of motivation to abstain from alcohol, and in helping patients to avoid relapses in heavy drinking when entered in an LT program.
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Affiliation(s)
- Fabio Caputo
- Department of Internal Medicine, SS Annunziata Hospital, University of Ferrara, Cento, Ferrara, Italy
| | - Gianni Testino
- Unit of Addiction and Hepatology, Alcohological Regional Center, ASL3 - IRCCS San Martino Hospital, Genoa, Italy -
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27
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Greenberg R, Goldberg A, Anthony S, Buchman DZ, Delaney S, Gruben V, Holdsworth S, Le Foll B, Leung M, Lien D, Lynch MJ, Selzner N, Chandler JA, Fortin MC. Canadian Society of Transplantation White Paper: Ethical and Legal Considerations for Alcohol and Cannabis Use in Solid Organ Listing and Allocation. Transplantation 2021; 105:1957-1964. [PMID: 33587429 PMCID: PMC8376271 DOI: 10.1097/tp.0000000000003618] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 11/16/2020] [Accepted: 11/20/2020] [Indexed: 11/26/2022]
Abstract
Alcohol and cannabis use as a contraindication to organ transplantation is a controversial issue. Until recently, patients in Canada with alcohol-associated liver disease were required to demonstrate abstinence for 6 mo to receive a liver transplant. There is no equivalent rule that is applied consistently for cannabis use. There is some evidence that alcohol and cannabis use disorder pretransplant could be associated with worse outcomes posttransplantation. However, early liver transplantation for patients with alcohol-associated liver disease in France and in the United States has led to challenges of the 6-mo abstinence rule in Canada in the media. It has also resulted in several legal challenges arguing that the rule violates human rights laws regarding discrimination in the provision of medical services and that the rule is also unconstitutional (this challenge is still before the court). Recent legalization of cannabis use for adults in Canada has led to questions about the appropriateness of limiting transplant access based on cannabis use. The ethics committee of the Canadian Society of Transplantation was asked to provide an ethical analysis of cannabis and alcohol abstinence policies. Our conclusions were as follows: neither cannabis use nor the 6-mo abstinence rule for alcohol use should be an absolute contraindication to transplantation, and transplant could be offered to selected patients, further research should be conducted to ensure evidence-based policies; and the transplant community has a duty not to perpetuate stigma associated with alcohol and cannabis use disorders.
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Affiliation(s)
- Rebecca Greenberg
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Mount Sinai Hospital, Toronto, ON, Canada
| | - Aviva Goldberg
- Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
- Canadian Donation and Transplantation Research Program, Edmonton, AB, Canada
| | - Samantha Anthony
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Canadian Donation and Transplantation Research Program, Edmonton, AB, Canada
- Factor-Inwentash Faculty of Social Work, University of Toronto, ON, Canada
| | - Daniel Z. Buchman
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
- University Health Network, Toronto, ON, Canada
| | | | - Vanessa Gruben
- Canadian Donation and Transplantation Research Program, Edmonton, AB, Canada
- Faculty of Law, University of Ottawa, Ottawa, ON, Canada
| | - Sandra Holdsworth
- Canadian Donation and Transplantation Research Program, Edmonton, AB, Canada
| | - Bernard Le Foll
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | | | - Dale Lien
- Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
| | - Marie-Josee Lynch
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Toronto General Research Institute, Toronto, ON, Canada
| | - Nazia Selzner
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Canadian Donation and Transplantation Research Program, Edmonton, AB, Canada
- Toronto General Research Institute, Toronto, ON, Canada
| | - Jennifer A. Chandler
- Canadian Donation and Transplantation Research Program, Edmonton, AB, Canada
- Faculty of Law, University of Ottawa, Ottawa, ON, Canada
| | - Marie-Chantal Fortin
- Canadian Donation and Transplantation Research Program, Edmonton, AB, Canada
- Centre de recherche du CHUM, Montreal, QC, Canada
- Faculty of Medicine, University of Montreal, QC, Canada
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28
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Herrick-Reynolds KM, Punchhi G, Greenberg RS, Strauss AT, Boyarsky BJ, Weeks-Groh SR, Krach MR, Anders RA, Gurakar A, Chen PH, Segev DL, King EA, Philosophe B, Ottman SE, Wesson RN, Garonzik-Wang JM, Cameron AM. Evaluation of Early vs Standard Liver Transplant for Alcohol-Associated Liver Disease. JAMA Surg 2021; 156:1026-1034. [PMID: 34379106 DOI: 10.1001/jamasurg.2021.3748] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Importance Traditionally, liver transplant (LT) for alcohol-associated liver disease (ALD) requires 6 months of abstinence. Although early LT before 6 months of abstinence has been associated with decreased mortality for decompensated ALD, this practice remains controversial and concentrated at a few centers. Objective To define patient, allograft, and relapse-free survival in early LT for ALD, and to investigate the association between these survival outcomes and early vs standard LT. Design, Setting, and Participants This cohort study analyzed all patients with ALD who underwent their first LT at a single academic referral center between October 1, 2012, and November 13, 2020. Patients with known pretransplant hepatocellular carcinoma, hepatitis B or C, or an alternative cause of liver failure were excluded. Follow-up period was defined as the time from LT to the most recent encounter with a transplant center or death. Exposures The exposure of interest was early LT, which was defined as less than 180 days of pre-LT abstinence. Standard LT was defined as 180 days or more of pre-LT abstinence. Patients were separated into early LT and standard LT by time from abstinence to LT. Main Outcomes and Measures The outcomes were patient, allograft, relapse-free, and hazardous relapse-free survival for patients who underwent early LT or standard LT. These groups were compared by log-rank testing of Kaplan-Meier estimates. Hazardous relapse was defined as binge, at-risk, or frequent drinking. Abstinence was reassessed at the most recent follow-up visit for all patients. Results Of the 163 patients with ALD included in this study, 88 (54%) underwent early LT and 75 (46%) underwent standard LT. This cohort had a mean (SD) age at transplant of 52 (10) years and was predominantly composed of 108 male patients (66%). Recipients of early LT vs standard LT were younger (median [interquartile range (IQR)] age, 49.7 [39.0-54.2] years vs 54.6 [48.7-60.0] years; P < .001) and had a higher median (IQR) Model for End-stage Liver Disease score at listing (35.0 [29.0-39.0] vs 20.0 [13.0-26.0]; P < .001). Both recipients of early LT and standard LT had similar 1-year patient survival (94.1% [95% CI, 86.3%-97.5%] vs 95.9% [95% CI, 87.8%-98.7%]; P = .60), allograft survival (92.7% [95% CI, 84.4%-96.7%] vs 90.5% [95% CI, 81.0%-95.3%]; P = .42), relapse-free survival (80.4% [95% CI, 69.1%-88.0%] vs 83.5% [95% CI, 72.2%-90.6%]; P = .41), and hazardous relapse-free survival (85.8% [95% CI, 75.1%-92.2%] vs 89.6% [95% CI, 79.5%-94.9%]; P = .41). Conclusions and Relevance Adherence to the 6-month rule was not associated with superior patient survival, allograft survival, or relapse-free survival among selected patients. This finding suggests that patients with ALD should not be categorically excluded from LT solely on the basis of 6 months of abstinence, but rather alternative selection criteria should be identified that are based on need and posttransplant outcomes.
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Affiliation(s)
- Kayleigh M Herrick-Reynolds
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Surgery, Walter Reed National Military Medical Center, Bethesda, Maryland
| | - Gopika Punchhi
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Ross S Greenberg
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Alexandra T Strauss
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Brian J Boyarsky
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Sharon R Weeks-Groh
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Michelle R Krach
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Robert A Anders
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Ahmet Gurakar
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Po-Hung Chen
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Dorry L Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland
| | - Elizabeth A King
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Benjamin Philosophe
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Shane E Ottman
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Russell N Wesson
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | - Andrew M Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
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29
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Van Melkebeke L, Korf H, Tsochatzis EA, van der Merwe S, Nevens F, Verbeek J. Treatment of severe alcoholic hepatitis: A systematic review. Curr Opin Pharmacol 2021; 60:91-101. [PMID: 34365226 DOI: 10.1016/j.coph.2021.06.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 06/16/2021] [Accepted: 06/28/2021] [Indexed: 12/15/2022]
Abstract
Severe alcoholic hepatitis is the most severe form of alcohol-related liver disease. Corticosteroids remain the first choice of treatment. However, they are only effective in a subset of patients and are associated with an increased infection risk. Furthermore, nonresponders to corticosteroids have a poor prognosis with a mortality of 70% over 6 months. As such, there is a high need for a more personalized use of corticosteroids and the development and identification of alternative therapeutic strategies. In this review, we summarize the recent and ongoing randomized controlled trials concerning the treatment of severe alcoholic hepatitis.
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Affiliation(s)
- Lukas Van Melkebeke
- Laboratory of Hepatology, Department of Chronic Diseases and Metabolism, Catholic University of Leuven, Belgium; Department of Gastroenterology & Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Hannelie Korf
- Laboratory of Hepatology, Department of Chronic Diseases and Metabolism, Catholic University of Leuven, Belgium
| | - Emmanuel A Tsochatzis
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, United Kingdom
| | - Schalk van der Merwe
- Laboratory of Hepatology, Department of Chronic Diseases and Metabolism, Catholic University of Leuven, Belgium; Department of Gastroenterology & Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Frederik Nevens
- Laboratory of Hepatology, Department of Chronic Diseases and Metabolism, Catholic University of Leuven, Belgium; Department of Gastroenterology & Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Jef Verbeek
- Laboratory of Hepatology, Department of Chronic Diseases and Metabolism, Catholic University of Leuven, Belgium; Department of Gastroenterology & Hepatology, University Hospitals Leuven, Leuven, Belgium.
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30
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Abstract
The incidence of alcoholic hepatitis is increasing while the mortality rate remains high. The single current available therapy for severe alcoholic hepatitis is administration of corticosteroids for patients with severe alcoholic hepatitis, which has demonstrated limited benefits, providing a short-term mortality benefit with a marginal response rate. There is a need for developing safe and effective therapies. This article reviews novel therapies targeting various mechanisms in the pathogenesis of alcoholic hepatitis, such as the gut-liver axis, inflammatory cascade, oxidative stress, and hepatic regeneration. Current ongoing clinical trials for alcoholic hepatitis also are described.
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Affiliation(s)
- Ma Ai Thanda Han
- Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, 185 South Orange Avenue, H-526, Newark, NJ 07103, USA
| | - Nikolaos Pyrsopoulos
- Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, 185 South Orange Avenue, H-536, Newark, NJ 07103, USA.
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31
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Bhatti S, Kim D, Ahmed A, Cholankeril G. Current Trends in Liver Transplantation for Alcoholic Hepatitis. Clin Liver Dis 2021; 25:625-634. [PMID: 34229844 DOI: 10.1016/j.cld.2021.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Liver transplantation (LT) for alcohol-related or alcoholic hepatitis (AH) remains a controversial treatment option. However, recent studies have shown promising outcomes for LT in a subgroup of patients with AH. Considering these emerging data, LT as definitive therapy for severe AH refractory to medical management is gaining recognition. However, concerns of alcohol recidivism pose a significant barrier to perform LT for this indication. Predictive models can be utilized to develop a selection criterion to identify suitable candidates for LT. Hence, carefully selected patients with severe AH and low risk of alcohol relapse can be considered for LT.
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Affiliation(s)
- Sundus Bhatti
- Baylor College of Medicine, Section of Gastroenterology and Hepatology, 6620 Main Street, Suite 1450, Houston, TX 77030, USA; Baylor College of Medicine, Division of Abdominal Transplantation, Houston, TX, USA
| | - Donghee Kim
- Stanford University School of Medicine, Division of Gastroenterology and Hepatology, 750 Welch Road, #210, Stanford, CA 94304, USA
| | - Aijaz Ahmed
- Stanford University School of Medicine, Division of Gastroenterology and Hepatology, 750 Welch Road, #210, Stanford, CA 94304, USA
| | - George Cholankeril
- Baylor College of Medicine, Section of Gastroenterology and Hepatology, 6620 Main Street, Suite 1450, Houston, TX 77030, USA; Baylor College of Medicine, Division of Abdominal Transplantation, Houston, TX, USA.
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32
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Abstract
IMPORTANCE Alcohol-associated liver disease results in cirrhosis in approximately 10% to 20% of patients. In 2017, more than 2 million people had alcohol-associated cirrhosis in the US. Alcohol-associated liver disease is the primary cause of liver-related mortality and the leading indication for liver transplant, representing 40% to 50% of all liver transplant in high-income countries. OBSERVATIONS Steatosis, alcoholic hepatitis, and fibrosis are the 3 pathologic findings that are associated with progression to cirrhosis, with highest risk in patients with alcoholic hepatitis. The amount and duration of alcohol consumption, female sex, obesity, and specific genetic polymorphisms such as patatin-like phospholipase domain protein 3, membrane bound O-acyltransferase, and transmembrane 6 superfamily member 2 genes are risk factors for alcohol-associated liver disease progression. Ten-year survival of patients with alcohol-associated liver disease is 88% among those who are abstinent and 73% for those who relapse to alcohol consumption. Symptomatic alcoholic hepatitis is characterized by rapid onset of jaundice and a 30% risk of mortality 1 year after diagnosis. Severe alcoholic hepatitis, defined as a modified discriminant function score greater than or equal to 32 or Model for End-Stage Liver Disease score (starts at 6 and capped at 40; worst = 40) greater than 20, is associated with the development of acute-on-chronic liver failure and multiorgan failure. Corticosteroid therapy is associated with improved 1-month survival from 65% in untreated patients to 80% in treated patients. Early liver transplant may be appropriate in highly select patients with severe alcoholic hepatitis who do not respond to medical therapy. In patients with decompensated cirrhosis, liver transplant should be considered if the Model for End-Stage Liver Disease score remains greater than 17 after 3 months of alcohol abstinence. Between 2014 and 2019, the proportion of patients waiting for liver transplantation who had alcohol-associated liver disease increased from 22% to 40%. Alcohol-associated cirrhosis accounted for approximately 27% of 1.32 million deaths worldwide related to cirrhosis in 2017. CONCLUSIONS AND RELEVANCE Alcohol-associated liver disease is among the most common liver diseases and more than 2 million people in the US in 2017 had alcohol-associated cirrhosis. Corticosteroid therapy improves survival in select patients with severe alcoholic hepatitis. Liver transplantation is the most effective therapy in patients with decompensated liver disease.
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Affiliation(s)
- Ashwani K Singal
- University of South Dakota Sanford School of Medicine, Sioux Falls
- Avera Transplant Institute, Sioux Falls, South Dakota
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33
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García-Alanís M, Toapanta-Yanchapaxi L, Vilatobá M, Cruz-Martínez R, Contreras AG, López-Yáñez S, Flores-García N, Marquéz-Guillén E, García-Juárez I. Psychosocial evaluation for liver transplantation: A brief guide for gastroenterologists. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2021; 86:172-187. [PMID: 33771379 DOI: 10.1016/j.rgmx.2020.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 12/09/2020] [Accepted: 12/27/2020] [Indexed: 06/12/2023]
Abstract
Liver transplantation is a lifesaving treatment that improves survival and quality of life. The procedure requires adequate transplant candidate selection carried out by a multidisciplinary team. Psychosocial evaluation is a necessary part of recipient selection and its primary aims are to identify problems and psychosocial needs of the patient and his/her family, to improve transplantation outcomes. Different psychosocial conditions are considered risk factors for morbidity and mortality after transplantation. The presence of those factors per se is not an absolute contraindication, thus adequate evaluation promotes equal access to healthcare, improves results, and optimizes resources. The present review provides an overview of and guidelines for the most important psychosocial issues during the pretransplantation phase.
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Affiliation(s)
- M García-Alanís
- Departamento de Neurología y Psiquiatría, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX, México.
| | - L Toapanta-Yanchapaxi
- Departamento de Neurología y Psiquiatría, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX, México
| | - M Vilatobá
- Departamento de Trasplantes, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX, México
| | - R Cruz-Martínez
- Departamento de Trasplantes, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX, México
| | - A G Contreras
- Departamento de Trasplantes, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX, México
| | - S López-Yáñez
- Departamento de Trabajo Social, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX, México
| | - N Flores-García
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX, México
| | - E Marquéz-Guillén
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX, México
| | - I García-Juárez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, CDMX, México
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García-Alanís M, Toapanta-Yanchapaxi L, Vilatobá M, Cruz-Martínez R, Contreras A, López-Yáñez S, Flores-García N, Marquéz-Guillén E, García-Juárez I. Psychosocial evaluation for liver transplantation: A brief guide for gastroenterologists. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2021. [DOI: 10.1016/j.rgmxen.2020.12.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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35
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Innovations in liver transplantation in 2020, position of the Belgian Liver Intestine Advisory Committee (BeLIAC). Acta Gastroenterol Belg 2021; 84:347-359. [PMID: 34217187 DOI: 10.51821/84.2.347] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver transplantation (LT) remains the only curative option for patients suffering from end-stage liver disease, acute liver failure and selected hepatocellular carcinomas and access to the LT-waiting list is limited to certain strict indications. However, LT has shown survival advantages for patients in certain indications such as acute alcoholic hepatitis, hepatocellular carcinoma outside Milan criteria and colorectal cancer metastases. These newer indications increase the pressure in an already difficult context of organ shortage. Strategies to increase the transplantable organ pool are therefore needed. We will discuss here the use of HCV positive grafts as the use of normothermic isolated liver perfusion. Belgian Liver Intestine Advisory Committee (BeLIAC) from the Belgian Transplant Society (BTS) aims to guarantee the balance between the new indications and the available resources.
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36
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Testino G, Pellicano R, Caputo F. Severe acute alcohol-related hepatitis and liver transplantation: yes or no? Minerva Surg 2021; 76:2-4. [PMID: 33754586 DOI: 10.23736/s2724-5691.20.08713-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Gianni Testino
- Unit of Addiction and Hepatology, Alcohological Regional Center, ASL3, IRCCS San Martino University Hospital, Genoa, Italy -
| | | | - Fabio Caputo
- Unit of Internal Medicine, Ospedale di Cento, University of Ferrara, Ferrara, Italy
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Becker JH, Shemesh E, Shenoy A, Posillico A, Knight CS, Kim SK, Florman SS, Schiano T, Annunziato RA. The Utility of a Pre-Transplant Psychosocial Evaluation in Predicting Post-Liver Transplant Outcomes. Prog Transplant 2020; 31:4-12. [PMID: 33272096 DOI: 10.1177/1526924820978605] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
BACKGROUND There is insufficient evidence about the ability of pretransplant psychosocial evaluations to predict posttransplant outcomes. While standardized assessments were developed to increase predictive validity, it is unclear whether the risk scores they yield predict outcomes. We investigated if the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT), a scaling approach to those assessments, would have been a superior predictor than the standard psychosocial evaluation. METHODS In this retrospective study, medical records of 182 adult liver transplant recipients who were at least 1 year posttransplant and prescribed tacrolimus for immunosuppression were analyzed. Regression analyses predicted outcomes of interest, including immunosuppressant nonadherence and biopsy-proven rejection, obtained 1-year posttransplant to time of data collection. Nonadherence was determined using the medication level variability index (MLVI). RESULTS Approximately 49% of patients had MLVI > 2.5, suggestive of nonadherence, and 15% experienced rejection. SIPAT total score did not predict adherence either using the continuous (P = .70), or dichotimized score, above or below > 2.5 (P = .14), or rejection (P = 0.87). Using a SIPAT threshold (total score > 69) did not predict adherence (p = .16) nor was a superior predictor of the continuous adherence score (P = .45), MLVI > 2.5 (P = .42), or rejection (P = 0.49), than the standard evaluation. CONCLUSION Our findings suggest that the SIPAT is unable to predict 2 of the most important outcomes in this population, immunosuppressant adherence and rejection. Research efforts should attempt to evaluate the best manner to use psychosocial evaluations.
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Affiliation(s)
- Jacqueline H Becker
- Department of Medicine, 5925Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Department of Pediatrics, 5925Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Eyal Shemesh
- Department of Pediatrics, 5925Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Akhil Shenoy
- Center for Liver Disease and Transplantation, 21611Columbia University Medical Center, New York, NY, USA
| | - Ailie Posillico
- Department of Psychology, 5923Fordham University, Bronx, NY, USA
| | | | - Se-Kang Kim
- Department of Psychology, 5923Fordham University, Bronx, NY, USA
| | - Sander S Florman
- 52100Recanati/Miller Transplantation Institute/Division of Liver Disease, Mount Sinai Medical Center, New York, NY, USA
| | - Thomas Schiano
- 52100Recanati/Miller Transplantation Institute/Division of Liver Disease, Mount Sinai Medical Center, New York, NY, USA
| | - Rachel A Annunziato
- Department of Pediatrics, 5925Icahn School of Medicine at Mount Sinai, New York, NY, USA.,52100Recanati/Miller Transplantation Institute/Division of Liver Disease, Mount Sinai Medical Center, New York, NY, USA
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38
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Baig M, Walayat S, Dhillon S, Puli S. Efficacy of Granulocyte Colony Stimulating Factor in Severe Alcoholic Hepatitis: A Systematic Review and Meta-Analysis. Cureus 2020; 12:e10474. [PMID: 33083176 PMCID: PMC7567328 DOI: 10.7759/cureus.10474] [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: 08/27/2020] [Accepted: 09/15/2020] [Indexed: 11/05/2022] Open
Abstract
Background Severe alcoholic hepatitis is a condition with a very high mortality rate and there is a paucity of evidence regarding efficacy and safety of most available therapeutic options. The present systematic review and meta-analysis aims to assess the survival benefit of granulocyte colony stimulating factor (G-CSF) in patients with severe alcoholic hepatitis. Methods Studies involving adult patients receiving G-CSF for severe alcoholic hepatitis were searched in MEDLINE, Ovid journals, MEDLINE nonindexed citations, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. Pooling was conducted by both fixed and random effects model. Results The initial search identified 543 reference articles; of these 24 relevant articles were selected and reviewed. Data was extracted from four studies (n = 136) which met the inclusion criteria. In the pooled analysis, the 90-day survival in the G-CSF group was 80.03% (95% CI = 69.93-88.49) compared to 40.92% (95% CI = 29.76-52.58) in the Standard Medical Therapy (SMT) group. At 28 days, the Model for End-Stage Liver Disease (MELD) score lowered by 4.89 (95% CI = 4.13-5.64) in the G-CSF group compared to 4.00 (95% CI = 3.25-4.75) in the SMT group. Child-Turcotte-Pugh score declined by 2.26 (95% CI = 1.90-2.63) in the G-CSF group after 28 days compared to 0.91 (95% CI = 0.59-1.23) in the SMT group. At 28 days, Maddrey Discriminant Function score lowered by 39.79 (95% CI = 34.22-45.36) in the G-CSF group compared to 12.39 (95% CI = 6.90-17.88) in the SMT group. Conclusions In patients with severe alcoholic hepatitis, G-CSF therapy resulted in significantly improved 90-day survival compared to SMT. It also demonstrated significant reduction in severity indices (Child-Turcotte-Pugh, MELD, and Maddrey discriminant function) after 28 days of treatment. There certainly is a need for further studies, including development of personalized therapeutic dosing schedules, for G-CSF administration.
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Affiliation(s)
- Muhammad Baig
- Gastroenterology, OSF St. Francis Medical Center/University of Illinois College of Medicine at Peoria, Peoria, USA
| | - Saqib Walayat
- Gastroenterology, OSF St. Francis Medical Center/University of Illinois College of Medicine at Peoria, Peoria, USA
| | - Sonu Dhillon
- Gastroenterology, OSF St. Francis Medical Center/University of Illinois College of Medicine at Peoria, Peoria, USA
| | - Srinivas Puli
- Gastroenterology, OSF St. Francis Medical Center/University of Illinois College of Medicine at Peoria, Peoria, USA
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39
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Dubois M, Sciarra A, Trépo E, Marot A, Saldarriaga J, Moreno C, Sempoux C, Deltenre P. Histologic parameter score does not predict short-term survival in severe alcoholic hepatitis. United European Gastroenterol J 2020; 8:1003-1012. [PMID: 32778003 DOI: 10.1177/2050640620949737] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AND AIM The alcoholic hepatitis histologic score has been proposed as a new prognostic tool to assess the risk of death in alcoholic hepatitis. We aimed to evaluate its prognostic value in patients with severe alcoholic hepatitis. METHODS Liver biopsies were analysed independently by two pathologists according to the alcoholic hepatitis histologic score. The Laennec staging system was also used to evaluate fibrosis. RESULTS One hundred and seven patients were included, and 89% of the patients received corticosteroids. The alcoholic hepatitis histologic score was available in 105 patients. Histologic scoring showed mild, moderate and severe scores in 10, 29 and 66 patients, respectively. Laennec staging was available for 53 patients, among whom 49 had cirrhosis, including 7 with Laennec 4A, 15 with 4B and 27 with 4C. Survival rates in mild, moderate and severe alcoholic hepatitis histologic score groups were 90%, 72% and 69% at 28 days (p = 0.6), 80%, 52% and 63% at 3 months (p = 0.3), and 70%, 41% and 58% at 6 months (p = 0.3), respectively. Within the alcoholic hepatitis histologic score, fibrosis demonstrated the best interobserver reproducibility (agreement = 100%, Κ = 1.00). Compared to patients with Laennec 4B or 4C cirrhosis, survival rates for patients without cirrhosis or with Laennec 4A cirrhosis were 100% vs 83% at 28 days (p = 0.16), 91% vs 68% at 3 months (p = 0.13), and 82% vs 64% at 6 months (p = 0.2), respectively. In multivariate analysis adjusted for age and for model for end-stage liver disease score, the alcoholic hepatitis histologic score and Laennec stage were not associated with 6-month mortality. CONCLUSIONS The alcoholic hepatitis histologic score is not predictive of short-term survival in this cohort of patients with severe alcoholic hepatitis.
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Affiliation(s)
- Margaux Dubois
- Division of Gastroenterology and Hepatology, University of Lausanne, Lausanne, Switzerland
| | - Amedeo Sciarra
- Department of Clinical Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Eric Trépo
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Université Libre de Bruxelles, Brussels, Belgium.,Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
| | - Astrid Marot
- Department of Gastroenterology and Hepatology, Université Catholique de Louvain, Yvoir, Belgium
| | - Joan Saldarriaga
- Department of Clinical Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Christophe Moreno
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Université Libre de Bruxelles, Brussels, Belgium.,Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
| | - Christine Sempoux
- Department of Clinical Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Pierre Deltenre
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Université Libre de Bruxelles, Brussels, Belgium.,Department of Gastroenterology and Hepatology, clinique Saint-Luc, Belgium
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Velarde-Ruiz Velasco JA, Higuera-de la Tijera MF, Castro-Narro GE, Zamarripa-Dorsey F, Abdo-Francis JM, Aiza Haddad I, Aldana Ledesma JM, Bielsa-Fernández MV, Cerda-Reyes E, Cisneros-Garza LE, Contreras-Omaña R, Reyes-Dorantes A, Fernández-Pérez NJ, García-Jiménez ES, Icaza-Chávez ME, Kershenobich-Stalnikowitz D, Lira-Pedrín MA, Moreno-Alcántar R, Pérez-Hernández JL, Ramos-Gómez MV, Rizo-Robles MT, Solana-Sentíes S, Torre-Delgadillo A. The Mexican consensus on alcoholic hepatitis. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2020; 85:332-353. [PMID: 32532534 DOI: 10.1016/j.rgmx.2020.04.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 04/07/2020] [Indexed: 06/11/2023]
Abstract
Alcoholic hepatitis is a frequent condition in the Mexican population. It is characterized by acute-on-chronic liver failure, important systemic inflammatory response, and multiple organ failure. The severe variant of the disease implies elevated mortality. Therefore, the Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Hepatología brought together a multidisciplinary team of health professionals to formulate the first Mexican consensus on alcoholic hepatitis, carried out utilizing the Delphi method and resulting in 37 recommendations. Alcohol-related liver disease covers a broad spectrum of pathologies that includes steatosis, steatohepatitis, different grades of fibrosis, and cirrhosis and its complications. Severe alcoholic hepatitis is defined by a modified Maddrey's discriminant function score ≥ 32 or by a Model for End-Stage Liver Disease (MELD) score equal to or above 21. There is currently no specific biomarker for its diagnosis. Leukocytosis with neutrophilia, hyperbilirubinemia (> 3 mg/dL), AST > 50 U/l (< 400 U/l), and an AST/ALT ratio > 1.5-2 can guide the diagnosis. Abstinence from alcohol, together with nutritional support, is the cornerstone of treatment. Steroids are indicated for severe disease and have been effective in reducing the 28-day mortality rate. At present, liver transplantation is the only life-saving option for patients that are nonresponders to steroids. Certain drugs, such as N-acetylcysteine, granulocyte-colony stimulating factor, and metadoxine, can be adjuvant therapies with a positive impact on patient survival.
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Affiliation(s)
- J A Velarde-Ruiz Velasco
- Servicio de Gastroenterología; Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México.
| | - M F Higuera-de la Tijera
- Servicio de Gastroenterología, Hospital General de México Dr. Eduardo Liceaga, Ciudad de México, México
| | - G E Castro-Narro
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | | | - I Aiza Haddad
- Clínica de Enfermedades Hepáticas, Hospital Ángeles Lomas, Estado de México, México
| | - J M Aldana Ledesma
- Servicio de Gastroenterología; Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México
| | | | | | | | - R Contreras-Omaña
- Centro de Investigación en Enfermedades Hepáticas y Gastroenterología, Pachuca, Hidalgo, México
| | | | | | - E S García-Jiménez
- Servicio de Gastroenterología; Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Jalisco, México
| | | | | | - M A Lira-Pedrín
- Servicio de Medicina Interna y Gastroenterología. Hospital y Centro Médico del Prado, Tijuana, Baja California, México
| | - R Moreno-Alcántar
- Unidad Médica de Alta Especialidad, Hospital de Especialidades CMN SXXI, Ciudad de México, México
| | - J L Pérez-Hernández
- Servicio de Gastroenterología, Hospital General de México Dr. Eduardo Liceaga, Ciudad de México, México; Hospital Central Sur de Alta Especialidad Petróleos Mexicanos, Ciudad de México, México
| | - M V Ramos-Gómez
- Centro Médico Nacional 20 de Noviembre, Ciudad de México, México
| | - M T Rizo-Robles
- Unidad Médica de Alta Especialidad, Hospital de Especialidades CMN SXXI, Ciudad de México, México
| | | | - A Torre-Delgadillo
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
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Velarde-Ruiz Velasco J, Higuera-de la Tijera M, Castro-Narro G, Zamarripa-Dorsey F, Abdo-Francis J, Haddad IA, Aldana Ledesma J, Bielsa-Fernández M, Cerda-Reyes E, Cisneros-Garza L, Contreras-Omaña R, Reyes-Dorantes A, Fernández-Pérez N, García-Jiménez E, Icaza-Chávez M, Kershenobich-Stalnikowitz D, Lira-Pedrín M, Moreno-Alcántar R, Pérez-Hernández J, Ramos-Gómez M, Rizo-Robles M, Solana-Sentíes S, Torre-Delgadillo A. The Mexican consensus on alcoholic hepatitis. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2020. [DOI: 10.1016/j.rgmxen.2020.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Marot A, Moreno C, Deltenre P. Liver transplant for alcoholic hepatitis: a current clinical overview. Expert Rev Gastroenterol Hepatol 2020; 14:591-600. [PMID: 32511039 DOI: 10.1080/17474124.2020.1775579] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Current management of severe alcoholic hepatitis is based on corticosteroid therapy and abstinence from alcohol. As liver transplantation is lifesaving in alcoholic hepatitis patients at high risk of early death, refractory alcoholic hepatitis has become a new indication for liver transplantation in highly selected non-responders to corticosteroids. AREAS COVERED This review summarizes the conditions under which liver transplantation may be considered, the available data on liver transplantation for refractory alcoholic hepatitis and explores the ethical considerations surrounding the use of liver transplantation in these patients. EXPERT OPINION Selection of candidates should be made according to available scientific results on post-liver transplantation outcomes and the risk of alcohol relapse. Currently, a strict selection process based on a good psychosocial profile, including social stability, no previous treatments for alcohol dependence, no current drug use, and no co-existing severe mental disorder, seems to be the best way to manage these issues. Well-defined selection criteria for candidate selection and accurate tools to predict alcohol relapse after liver transplantation are still needed.
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Affiliation(s)
- Astrid Marot
- Department of Gastroenterology and Hepatology CHU UCL Namur, Université Catholique De Louvain , Yvoir, Belgium
| | - Christophe Moreno
- Department of Gastroenterology Hepatopancreatology, and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre De Bruxelles , Brussels, Belgium
| | - Pierre Deltenre
- Department of Gastroenterology Hepatopancreatology, and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre De Bruxelles , Brussels, Belgium.,Department of Gastroenterology and Hepatology, Clinique St Luc , Bouge, Belgium
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43
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Marot A, Singal AK, Moreno C, Deltenre P. Granulocyte colony-stimulating factor for alcoholic hepatitis: A systematic review and meta-analysis of randomised controlled trials. JHEP Rep 2020; 2:100139. [PMID: 32775975 PMCID: PMC7396826 DOI: 10.1016/j.jhepr.2020.100139] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 06/06/2020] [Accepted: 06/08/2020] [Indexed: 12/11/2022] Open
Abstract
Background & Aims Granulocyte colony-stimulating factor (G-CSF) treatment has been proposed as a therapeutic option for patients with severe alcoholic hepatitis (AH). The aim of this study was to synthesise available evidence on the efficacy of G-CSF in AH. Methods This is a meta-analysis of randomised controlled trials evaluating the risk of death at 90 days and the risk of infection. Results Seven studies were included. Of a total of 396 patients, 336 had AH, 197 patients were treated with G-CSF, and 199 received placebo or pentoxifylline. In overall meta-analysis, G-CSF therapy was associated with a reduced risk of death at 90 days (odds ratio [OR] 0.28; 95% CI 0.09–0.88; p = 0.03). There was high heterogeneity between studies (p <0.001; I2 = 80%). Five studies were performed in Asia and 2 in Europe. In the subgroup analysis of studies performed in Asia, G-CSF was associated with a reduced risk of death (OR 0.15; 95% CI 0.08–0.28; p <0.001; heterogeneity: p = 0.5, I2 = 0%). In European studies, G-CSF tended to increase mortality compared with controls, although the difference was not significant (OR 1.89; 95% CI 0.90–3.98; p = 0.09; heterogeneity: p = 0.8, I2 = 0%). In Asian studies, occurrence of infection was less frequent in G-CSF patients than in controls (OR 0.12; 95% CI 0.06–0.23; p <0.001; heterogeneity: p = 0.7, I2 = 0%), whilst in European studies, this occurrence was not statistically different (OR 0.92; 95% CI 0.50–1.68; p = 0.78; heterogeneity: p = 0.5, I2 = 0%). In sensitivity analyses, excluding studies that included patients with acute-on-chronic liver failure (ACLF) other than AH, patients with less severe AH, or patients with non-response to corticosteroids, results were similar to those of overall analyses, both for mortality and occurrence of infection. Conclusions Granulocyte colony-stimulating factor therapy may improve the prognosis of patients with severe AH. However, owing to the high heterogeneity observed in the overall analysis caused by conflicting results between the Asian and European studies, G-CSF cannot currently be recommended for AH, particularly in Europe. Whether these differences can be explained by ethnic differences or disparities in patient selection and disease severity remains unclear. Lay summary The main finding of this meta-analysis is that the use of granulocyte colony-stimulating factor (G-CSF) is associated with a mortality reduction of more than 70% at 3 months amongst patients with alcoholic hepatitis (AH) compared with controls who did not receive this therapy. However, owing to the high heterogeneity observed in the overall analysis caused by conflicting results between the Asian and European studies, G-CSF cannot currently be recommended for patients with AH, particularly in Europe. Whether these differences can be explained by ethnic differences or disparities in patient selection and disease severity remains unclear.
This meta-analysis reports pooled data from 7 studies on the use of G-CSF in patients with alcoholic hepatitis. The favourable effect of G-CSF was only encountered in Asian not European studies. Additional data are needed to clarify the usefulness of G-CSF in severe alcoholic hepatitis, particularly in Europe.
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Affiliation(s)
- Astrid Marot
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium
- Corresponding author. Address: Department of Gastroenterology and Hepatology, CHU UCL Namur, Université Catholique de Louvain, avenue Gaston Thérasse, 1, 5530 Yvoir, Belgium. Tel.: +32 81 42 32 72; fax: +32 81 42 32 54.
| | - Ashwani K. Singal
- Division of Transplant Hepatology, Avera Transplant Institute and Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, SD, USA
| | - Christophe Moreno
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Pierre Deltenre
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
- Department of Gastroenterology and Hepatology, Clinique St Luc, Bouge, Belgium
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Abstract
Although short- and medium-term outcomes after liver transplantation for alcohol-related liver disease (ARLD) are generally excellent and similar to outcomes for transplantation for other indications, a return to alcohol consumption commonly occurs even though rates of alcohol consumption after transplantation for ARLD are comparable to those seen in other indications. Transplant recipients should be questioned about alcohol use post-transplantation and, where appropriate, monitored; those drinking significant amounts should be offered treatment with the help of a multi-disciplinary team. Although short-term significant alcohol use is associated with an increased risk of non-compliance and rejection, medium-term outcomes are similar to other groups. Patients transplanted for ARLD have a greater risk of some de novo malignancies, especially of the lung and the upper GI tract. More work is required both to identify those at risk of a return to destructive patterns of alcohol use at an early stage and to develop effective treatments aimed at reaching and maintaining abstinence.
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Affiliation(s)
- James Neuberger
- Liver Unit, Queen Elizabeth Hospital, Birmingham, B15 2TH, UK.
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45
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Shipley LC, Singal AK. Liver transplantation for alcoholic hepatitis. Transl Gastroenterol Hepatol 2020; 5:26. [PMID: 32258530 DOI: 10.21037/tgh.2019.11.17] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 11/05/2019] [Indexed: 12/12/2022] Open
Abstract
Alcoholic hepatitis (AH) is associated with a high short-term mortality. Currently, most transplant centers require minimum six months of abstinence from alcohol use before considering liver transplant for patients with end stage liver disease. Some recent data are emerging on the benefits and safety of early liver transplantation for patients with severe AH, a population who cannot meet the minimum six months sobriety. This article reviews the current status, benefits, challenges, barriers, and future prospects on early liver transplantation in patients with severe, acute AH.
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Affiliation(s)
- Lindsey C Shipley
- Division of Internal Medicine, University of Alabama, Birmingham, AL, USA
| | - Ashwani K Singal
- Division of Gastroenterology and Hepatology, University of South Dakota, Avera McKennan University Health Center and Transplant Institute, Sioux Falls, SD, USA
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Ayyala-Somayajula D, Han H, Terrault NA. Selective use of liver transplantation for severe alcohol-associated hepatitis. Expert Rev Gastroenterol Hepatol 2020; 14:175-184. [PMID: 32077333 DOI: 10.1080/17474124.2020.1733414] [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] [Indexed: 10/25/2022]
Abstract
Introduction: Severe alcohol-associated hepatitis (sAH) portends high morbidity and mortality and there are no effective therapies for those ineligible or unresponsive to corticosteroids. Early liver transplantation (LT) defined as transplantation without a mandated period of sobriety, for sAH, is being increasingly considered as a rescue therapy.Areas covered: PubMed and manual searches were combined and last performed on 28 October 2019. Key search terms were 'alcoholic hepatitis', 'abstinence', 'alcohol relapse', and 'liver transplantation'. Terms were combined within each database. General reviews and references from published trials were also used.Expert opinion: Early LT is indicated in highly selected patients with sAH. While long-term data are sparse, 1 and 3-year survival post-transplantation are excellent and comparable to other liver diseases. Alcohol relapse is uncommon but approaches 10-25% at 3 years and if use is heavy and/or sustained leads to reduced survival. Thus, for continued application of transplantation for this indication, there is a need to further refine selection criteria and to optimize management of alcohol use disorder (AUD) in the transplant setting. Integral to advancing these objectives is the elimination of societal stigmatization and an acknowledgment that AUD is a medical condition that requires long-term management.
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Affiliation(s)
| | - Hyosun Han
- Department of Medicine, USC Keck School of Medicine, Los Angeles, CA, USA.,Division of Gastrointestinal and Liver Diseases, USC Keck School of Medicine, Los Angeles, CA, USA
| | - Norah A Terrault
- Department of Medicine, USC Keck School of Medicine, Los Angeles, CA, USA.,Division of Gastrointestinal and Liver Diseases, USC Keck School of Medicine, Los Angeles, CA, USA
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Deltenre P, Trépo E, Fujiwara N, Goossens N, Marot A, Dubois M, Spahr L, Henrion J, Moreno C, Hoshida Y. Gene signature-MELD score and alcohol relapse determine long-term prognosis of patients with severe alcoholic hepatitis. Liver Int 2020; 40:565-570. [PMID: 31568650 PMCID: PMC7056530 DOI: 10.1111/liv.14265] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 09/03/2019] [Accepted: 09/19/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND The gene-signature-model for end stage liver disease (gs-MELD) score has been shown to be a strong predictor of 6-month survival in severe alcoholic hepatitis (AH). Currently, only a few studies have evaluated the long-term prognosis of patients with severe AH. AIM To assess the prognostic value of the gs-MELD score at 5 years in patients with severe AH. METHODS Forty-eight consecutive patients with AH (25 males, median age 52 years [95% IC: 48-56]) were included. RESULTS The median gs-MELD score was 2.6 (95% CI: 2.2-3.0). According to the gs-MELD score, 22 patients (46%) were considered to have a poor prognosis. During a median follow-up of 29 months (95% CI: 4-43), 19 patients (40%) were abstinent and 24 patients (50%) died. At 5 years, rates of survival were 61% (95% CI: 41-81) and 26% (95% CI: 11-55) in patients with low and high gs-MELD scores (P = .001), and 81% (95% CI: 58-96) and 22% (95% CI: 10-47) in abstainers and in consumers (P < .001) respectively. In multivariable competing risk regression modelling, gs-MELD score (subdistribution hazard ratio: 5.78, 95% CI: 2.17-15.38, P < .001) and recurrent alcohol consumption (subdistribution hazard ratio: 12.18, 95% CI: 3.16-46.95, P < .001) were independently associated with 5-year mortality. CONCLUSIONS Both gs-MELD score and alcohol consumption drive AH long-term prognosis. The gs-MELD score may guide the development of molecularly targeted therapies in AH.
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Affiliation(s)
- Pierre Deltenre
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.,Department of Gastroenterology and Hepatology, Clinique St Luc, Bouge, Belgium,Correspondence: Pierre Deltenre, M.D., Ph.D., Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; ; Yujin Hoshida, M.D., Ph.D., Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA;
| | - Eric Trépo
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.,Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
| | - Naoto Fujiwara
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA
| | - Nicolas Goossens
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA.,Division of Gastroenterology and Hepatology, Geneva University Hospital, Geneva, Switzerland
| | - Astrid Marot
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium
| | - Margaux Dubois
- Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Laurent Spahr
- Division of Gastroenterology and Hepatology, Geneva University Hospital, Geneva, Switzerland
| | - Jean Henrion
- Department of Gastroenterology and Hepatology, Hôpital de Jolimont, Haine-Saint-Paul, Belgium
| | - Christophe Moreno
- Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.,Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
| | - Yujin Hoshida
- Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA.,Correspondence: Pierre Deltenre, M.D., Ph.D., Department of Gastroenterology, Hepatopancreatology, and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium; ; Yujin Hoshida, M.D., Ph.D., Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA;
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Singal AK, Satapathy SK, Reau N, Wong R, Kuo YF. Hepatitis C remains leading indication for listings and receipt of liver transplantation for hepatocellular carcinoma. Dig Liver Dis 2020; 52:98-101. [PMID: 31582326 DOI: 10.1016/j.dld.2019.08.022] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 08/19/2019] [Accepted: 08/24/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS With the availability of direct acting antivirals (DAA) for hepatitis C virus (HCV) infection, alcoholic liver disease (ALD) has evolved as the leading indication for listing and receipt of liver transplantation (LT) followed by non-alcoholic steatohepatitis and HCV infection. However, data are limited on etiology specific trends on listings and need for LT for hepatocellular carcinoma (HCC). METHODS We analyzed UNOS database to examine etiology specific listings and receipt of LT for patients with and without HCC. Listings and receipt of LT in the pre-DAA (2007-2012) era were compared to the DAA (2013-2018) era. RESULTS The analysis shows that among patients without HCV, there is a decreasing trend on the proportion of patients listed and transplanted for HCV, with simultaneous increase on listings and LT for NASH and ALD. Specifically for listings and transplants for HCC, the leading etiology remains HCV infection followed by NASH and ALD. The analysis also showed that LT for AH contributes to about 20% of increase in listings and receipt of LT for ALD.
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Affiliation(s)
- Ashwani K Singal
- University of South Dakota Sanford School of Medicine and Avera Transplant Institute, Sioux Falls, SD, USA; Division of Hepatology and Sandra Bass Center for Liver Diseases, Northwell Health, Manhasset, NY, USA; Division of Gastroenterology and Hepatology, Rush University Medical Center, Chicago, IL, USA; Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA; Department of Biostatistics and Preventive Medicine, University of Texas Medical Branch, Galveston, TX, USA.
| | - Sanjaya K Satapathy
- University of South Dakota Sanford School of Medicine and Avera Transplant Institute, Sioux Falls, SD, USA; Division of Hepatology and Sandra Bass Center for Liver Diseases, Northwell Health, Manhasset, NY, USA; Division of Gastroenterology and Hepatology, Rush University Medical Center, Chicago, IL, USA; Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA; Department of Biostatistics and Preventive Medicine, University of Texas Medical Branch, Galveston, TX, USA
| | - Nancy Reau
- University of South Dakota Sanford School of Medicine and Avera Transplant Institute, Sioux Falls, SD, USA; Division of Hepatology and Sandra Bass Center for Liver Diseases, Northwell Health, Manhasset, NY, USA; Division of Gastroenterology and Hepatology, Rush University Medical Center, Chicago, IL, USA; Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA; Department of Biostatistics and Preventive Medicine, University of Texas Medical Branch, Galveston, TX, USA
| | - Robert Wong
- University of South Dakota Sanford School of Medicine and Avera Transplant Institute, Sioux Falls, SD, USA; Division of Hepatology and Sandra Bass Center for Liver Diseases, Northwell Health, Manhasset, NY, USA; Division of Gastroenterology and Hepatology, Rush University Medical Center, Chicago, IL, USA; Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA; Department of Biostatistics and Preventive Medicine, University of Texas Medical Branch, Galveston, TX, USA
| | - Yong-Fang Kuo
- University of South Dakota Sanford School of Medicine and Avera Transplant Institute, Sioux Falls, SD, USA; Division of Hepatology and Sandra Bass Center for Liver Diseases, Northwell Health, Manhasset, NY, USA; Division of Gastroenterology and Hepatology, Rush University Medical Center, Chicago, IL, USA; Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Oakland, CA, USA; Department of Biostatistics and Preventive Medicine, University of Texas Medical Branch, Galveston, TX, USA
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49
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Asrani SK, Trotter J, Lake J, Ahmad A, Bonagura A, Cameron A, DiMartini A, Gonzalez S, Im G, Martin P, Mathurin P, Mellinger J, Rice JP, Shah V, Terrault N, Wall A, Winder S, Klintmalm G. Meeting Report: The Dallas Consensus Conference on Liver Transplantation for Alcohol Associated Hepatitis. Liver Transpl 2020; 26:127-140. [PMID: 31743578 PMCID: PMC8151800 DOI: 10.1002/lt.25681] [Citation(s) in RCA: 87] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 10/29/2019] [Indexed: 12/13/2022]
Abstract
Liver transplantation (LT) for alcohol associated hepatitis (AH) remains controversial. We convened a consensus conference to examine various aspects of LT for AH. The goal was not to unequivocally endorse LT for AH; instead, it was to propose recommendations for programs that perform or plan to perform LT for AH. Criteria were established to determine candidacy for LT in the setting of AH and included the following: (1) AH patients presenting for the first time with decompensated liver disease that are nonresponders to medical therapy without severe medical or psychiatric comorbidities; (2) a fixed period of abstinence prior to transplantation is not required; and (3) assessment with a multidisciplinary psychosocial team, including a social worker and an addiction specialist/mental health professional with addiction and transplantation expertise. Supporting factors included lack of repeated unsuccessful attempts at addiction rehabilitation, lack of other substance use/dependency, acceptance of diagnosis/insight with a commitment of the patient/family to sobriety, and formalized agreement to adhere to total alcohol abstinence and counseling. LT should be avoided in AH patients who are likely to spontaneously recover. Short-term and longterm survival comparable to other indications for LT must be achieved. There should not be further disparity in LT either by indication, geography, or other sociodemographic factors. Treatment of alcohol-use disorders should be incorporated into pre- and post-LT care. The restrictive and focused evaluation process described in the initial LT experience for AH worldwide may not endure as this indication gains wider acceptance at more LT programs. Transparency in the selection process is crucial and requires the collection of objective data to assess outcomes and minimize center variation in listing. Oversight of program adherence is important to harmonize listing practices and outcomes.
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Affiliation(s)
- Sumeet K Asrani
- Baylor University Medical Center, Dallas, Texas,Corresponding author: Sumeet K Asrani MD MSc, Associate Professor of Medicine, Baylor University Medical Center, Dallas Texas, , Tele: 214 820 8500, Fax: 214 820 0993
| | | | - Jack Lake
- University of Minnesota, Minneapolis, Minnesota
| | | | | | | | | | | | | | - Paul Martin
- University of Miami health system, Miami, Florida
| | - Philippe Mathurin
- Service d’Hépato-gastroentérologie, Hôpital Claude Huriez, Lille, France
| | | | | | | | - Norah Terrault
- University of Southern California, Los Angeles, California
| | - Anji Wall
- Baylor University Medical Center, Dallas, Texas
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50
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Testino G, Vignoli T, Patussi V, Scafato E, Caputo F. Management of end-stage alcohol-related liver disease and severe acute alcohol-related hepatitis: position paper of the Italian Society on Alcohol (SIA). Dig Liver Dis 2020; 52:21-32. [PMID: 31757596 DOI: 10.1016/j.dld.2019.09.017] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 08/28/2019] [Accepted: 09/23/2019] [Indexed: 02/07/2023]
Abstract
Worldwide, the prevalence of alcohol use disorder (AUD) is 20-30% in men and 10-15% in women, and cirrhosis due to alcohol-related liver disease (ALD) is responsible for 0.9% of global deaths and 47.9% of cirrhosis-related deaths. End-stage ALD (ESALD) is the final condition of alcohol-related cirrhosis, and severe acute alcohol-related hepatitis (SAAH) is a distinct clinical syndrome associated with the consumption of large amounts of alcohol. In some cases, ESALD, and SAAH may need liver transplantation (LT). Thus, the management of ESALD and SAAH in patients affected by AUD may be an essential part of the clinical skills for hepatologists. For these reasons, the national board of the Italian Society on Alcohol have reviewed the most recent data on the management of ESALD, SAAH and LT for ALD in patients with AUD, formulating a position paper with related recommendations regarding four issues of specific clinical interest in this field: (a) the management of hepatic encephalopathy in patients with AUD, and LT in patients with ESALD; (b) the management of SAAH; (c) the management of AUD in patients with ESALD and SAAH; (d) special populations: polydrug addicts.
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Affiliation(s)
- Gianni Testino
- Unit of Addiction and Hepatology ASL3 Liguria, San Martino Hospital, Genova, Italy
| | - Teo Vignoli
- Unit of Addiction Treatment, Lugo, Ravenna, Italy
| | | | - Emanuele Scafato
- National Observatory on Alcohol, National Institute of Health, Roma, Italy
| | - Fabio Caputo
- Department of Internal Medicine, SS Annunziata Hospital, Cento, Ferrara, Italy; "G. Fontana" Centre for the Study and Multidisciplinary Treatment of Alcohol Addiction, Department of Medical and Surgical Sciences, University of Bologna, Italy.
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