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Review Article| Volume 107, ISSUE 3, P533-554, May 2023

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Alcoholic Hepatitis

The Rising Epidemic
Published:February 20, 2023DOI:https://doi.org/10.1016/j.mcna.2022.12.005

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      References

        • Crabb D.W.
        • Bataller R.
        • Chalasani N.P.
        • et al.
        Standard Definitions and Common Data Elements for Clinical Trials in Patients With Alcoholic Hepatitis: Recommendation From the NIAAA Alcoholic Hepatitis Consortia.
        Gastroenterology. 2016; 150: 785-790
        • Maddrey W.C.
        • Boitnott J.K.
        • Bedine M.S.
        • et al.
        Corticosteroid therapy of alcoholic hepatitis.
        Gastroenterology. 1978; 75: 193-199
        • Philips C.A.
        • Augustine P.
        • Yerol P.K.
        • et al.
        Severe alcoholic hepatitis: current perspectives.
        HMER. 2019; 11: 97-108
        • Basra S.
        Definition, epidemiology and magnitude of alcoholic hepatitis.
        WJH. 2011; 3: 108
        • Shirazi F.
        • Singal A.K.
        • Wong R.J.
        Alcohol-associated Cirrhosis and Alcoholic Hepatitis Hospitalization Trends in the United States.
        J Clin Gastroenterol. 2021; 55: 174-179
        • Hirode G.
        • Saab S.
        • Wong R.J.
        Trends in the Burden of Chronic Liver Disease Among Hospitalized US Adults.
        JAMA Netw Open. 2020; 3: e201997
        • Liangpunsakul S.
        Clinical Characteristics and Mortality of Hospitalized Alcoholic Hepatitis Patients in the United States.
        J Clin Gastroenterol. 2011; 45: 714-719
        • Mandayam S.
        • Jamal M.M.
        • Morgan T.R.
        Epidemiology of Alcoholic Liver Disease.
        Semin Liver Dis. 2004; 24: 217-232
        • Doycheva I.
        • Watt K.D.
        • Rifai G.
        • et al.
        Increasing Burden of Chronic Liver Disease Among Adolescents and Young Adults in the USA: A Silent Epidemic.
        Dig Dis Sci. 2017; 62: 1373-1380
        • Alkhouri N.
        • Almomani A.
        • Le P.
        • et al.
        The prevalence of alcoholic and nonalcoholic fatty liver disease in adolescents and young adults in the United States: analysis of the NHANES database.
        BMC Gastroenterol. 2022; 22: 366
        • Tapper E.B.
        • Parikh N.D.
        Mortality due to cirrhosis and liver cancer in the United States, 1999-2016: observational study.
        BMJ. 2018; 362: k2817
        • Yeo Y.H.
        • He X.
        • Ting P.S.
        • et al.
        Evaluation of Trends in Alcohol Use Disorder–Related Mortality in the US Before and During the COVID-19 Pandemic.
        JAMA Netw Open. 2022; 5: e2210259
        • White A.M.
        • Castle I.J.P.
        • Powell P.A.
        • et al.
        Alcohol-Related Deaths During the COVID-19 Pandemic.
        JAMA. 2022; 327: 1704-1706
        • Sharma R.A.
        • Subedi K.
        • Gbadebo B.M.
        • et al.
        Alcohol Withdrawal Rates in Hospitalized Patients During the COVID-19 Pandemic.
        JAMA Netw Open. 2021; 4: e210422
        • Barbosa C.
        • Cowell A.J.
        • Dowd W.N.
        Alcohol Consumption in Response to the COVID-19 Pandemic in the United States.
        J Addict Med. 2021; 15: 341-344
        • Julien J.
        • Ayer T.
        • Tapper E.B.
        • et al.
        Effect of increased alcohol consumption during COVID-19 pandemic on alcohol-associated liver disease: A modeling study.
        Hepatology. 2022; 75: 1480-1490
        • Deutsch-Link S.
        • Jiang Y.
        • Peery A.F.
        • et al.
        Alcohol-Associated Liver Disease Mortality Increased From 2017 to 2020 and Accelerated During the COVID-19 Pandemic.
        Clin Gastroenterol Hepatol. 2022; 20 (e2): 2142-2144
        • Sohal A.
        • Khalid S.
        • Green V.
        • et al.
        The Pandemic Within the Pandemic.
        J Clin Gastroenterol. 2022; 56: e171-e175
        • Damjanovska S.
        • Karb D.B.
        • Cohen S.M.
        Increasing Prevalence and Racial Disparity of Alcohol-Related Gastrointestinal and Liver Disease During the COVID-19 Pandemic: A Population-Based National Study.
        J Clin Gastroenterol. 2022; (Publish Ahead of Print)
        • Gonzalez H.C.
        • Zhou Y.
        • Nimri F.M.
        • et al.
        Alcohol-related hepatitis admissions increased 50% in the first months of the COVID-19 pandemic in the USA.
        Liver Int. 2022; 42: 762-764
        • Shaheen A.A.
        • Kong K.
        • Ma C.
        • et al.
        Impact of the COVID-19 Pandemic on Hospitalizations for Alcoholic Hepatitis or Cirrhosis in Alberta, Canada.
        Clin Gastroenterol Hepatol. 2022; 20: e1170-e1179
        • Marlowe N.
        • Lam D.
        • Krebs W.
        • et al.
        Prevalence, co-morbidities, and in-hospital mortality of patients hospitalized with alcohol-associated hepatitis in the United States from 2015 to 2019.
        Alcohol Clin Exp Res. 2022; 46: 1472-1481
        • Dhanda A.D.
        Is liver biopsy necessary in the management of alcoholic hepatitis?.
        WJG. 2013; 19: 7825
        • Arab J.P.
        • Díaz L.A.
        • Baeza N.
        • et al.
        Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study.
        J Hepatol. 2021; 75: 1026-1033
        • Rahimi E.
        • Pan J.J.
        Prognostic models for alcoholic hepatitis.
        Biomark Res. 2015; 3: 20
        • Dominguez M.
        • Rincón D.
        • Abraldes J.G.
        • et al.
        A New Scoring System for Prognostic Stratification of Patients With Alcoholic Hepatitis.
        Am J Gastroenterol. 2008; 103: 2747-2756https://doi.org/10.1111/j.1572-0241.2008.02104.x
        • Morales-Arráez D.
        • Ventura-Cots M.
        • Altamirano J.
        • et al.
        The MELD Score Is Superior to the Maddrey Discriminant Function Score to Predict Short-Term Mortality in Alcohol-Associated Hepatitis: A Global Study.
        Am J Gastroenterol. 2022; 117: 301-310
        • Louvet A.
        • Naveau S.
        • Abdelnour M.
        • et al.
        The Lille model: A new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids.
        Hepatology. 2007; 45: 1348-1354
        • Mathurin P.
        • O’Grady J.
        • Carithers R.L.
        • et al.
        Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta-analysis of individual patient data.
        Gut. 2011; 60: 255-260
        • Garcia-Saenz-de-Sicilia M.
        • Duvoor C.
        • Altamirano J.
        • et al.
        A Day-4 Lille Model Predicts Response to Corticosteroids and Mortality in Severe Alcoholic Hepatitis.
        Am J Gastroenterol. 2017; 112: 306-315
        • Louvet A.
        • Labreuche J.
        • Artru F.
        • et al.
        Combining Data From Liver Disease Scoring Systems Better Predicts Outcomes of Patients With Alcoholic Hepatitis.
        Gastroenterology. 2015; 149 (e8): 398-406
        • Kulkarni K.
        • Tran T.
        • Medrano M.
        • et al.
        The Role of the Discriminant Factor in the Assessment and Treatment of Alcoholic Hepatitis.
        J Clin Gastroenterol. 2004; 38: 453-459
        • Hanouneh I.A.
        • Zein N.N.
        • Cikach F.
        • et al.
        The Breathprints in Patients with Liver Disease Identify Novel Breath Biomarkers in Alcoholic Hepatitis.
        Clin Gastroenterol Hepatol. 2014; 12: 516-523
        • Bissonnette J.
        • Altamirano J.
        • Devue C.
        • et al.
        A prospective study of the utility of plasma biomarkers to diagnose alcoholic hepatitis.
        Hepatology. 2017; 66: 555-563
        • Momen-Heravi F.
        • Saha B.
        • Kodys K.
        • et al.
        Increased number of circulating exosomes and their microRNA cargos are potential novel biomarkers in alcoholic hepatitis.
        J Transl Med. 2015; 13: 261
        • Atkinson S.R.
        • Grove J.I.
        • Liebig S.
        • et al.
        In Severe Alcoholic Hepatitis, Serum Keratin-18 Fragments Are Diagnostic, Prognostic, and Theragnostic Biomarkers.
        ACG. 2020; 115: 1857-1868
        • Brandl K.
        • Hartmann P.
        • Jih L.J.
        • et al.
        Dysregulation of serum bile acids and FGF19 in alcoholic hepatitis.
        J Hepatol. 2018; 69: 396-405
        • Sandahl T.D.
        • Grønbæk H.
        • Møller H.J.
        • et al.
        Hepatic Macrophage Activation and the LPS Pathway in Patients With Alcoholic Hepatitis: A Prospective Cohort Study.
        Am J Gastroenterol. 2014; 109: 1749-1756
        • Michelena J.
        • Altamirano J.
        • Abraldes J.G.
        • et al.
        Systemic Inflammatory Response and Serum Lipopolysaccharide Levels Predict Multiple Organ Failure and Death in Alcoholic Hepatitis.
        Hepatology. 2015; 62: 762-772
        • Gala K.S.
        • Vatsalya V.
        Emerging Noninvasive Biomarkers, and Medical Management Strategies for Alcoholic Hepatitis: Present Understanding and Scope.
        Cells. 2020; 9: 524
        • Cabré E.
        • Rodríguez-Iglesias P.
        • Caballería J.
        • et al.
        Short- and long-term outcome of severe alcohol-induced hepatitis treated with steroids or enteral nutrition: A multicenter randomized trial.
        Hepatology. 2000; 32: 36-42
        • Moreno C.
        • Deltenre P.
        • Senterre C.
        • et al.
        Intensive Enteral Nutrition Is Ineffective for Patients With Severe Alcoholic Hepatitis Treated With Corticosteroids.
        Gastroenterology. 2016; 150 (e8): 903-910
        • Singal A.K.
        • Bataller R.
        • Ahn J.
        • et al.
        ACG Clinical Guideline: Alcoholic Liver Disease.
        Am J Gastroenterol. 2018; 113: 175-194
        • Crabb D.W.
        • Im G.Y.
        • Szabo G.
        • et al.
        Diagnosis and Treatment of Alcohol-Associated Liver Diseases: 2019 Practice Guidance From the American Association for the Study of Liver Diseases.
        Hepatology. 2020; 71: 306-333
        • Thursz M.
        • Gual A.
        • Lackner C.
        • et al.
        EASL Clinical Practice Guidelines: Management of alcohol-related liver disease.
        J Hepatol. 2018; 69: 154-181
        • Singal A.K.
        • Walia I.
        • Singal A.
        • et al.
        Corticosteroids and pentoxifylline for the treatment of alcoholic hepatitis: Current status.
        World J Hepatol. 2011; 3: 205-210
        • Thursz M.R.
        • Richardson P.
        • Allison M.
        • et al.
        Prednisolone or Pentoxifylline for Alcoholic Hepatitis.
        N Engl J Med. 2015; 372: 1619-1628
        • Louvet A.
        • Thursz M.R.
        • Kim D.J.
        • et al.
        Corticosteroids Reduce Risk of Death Within 28 Days for Patients With Severe Alcoholic Hepatitis, Compared With Pentoxifylline or Placebo—a Meta-analysis of Individual Data From Controlled Trials.
        Gastroenterology. 2018; 155 (e8): 458-468
        • Louvet A.
        • Wartel F.
        • Castel H.
        • et al.
        Infection in patients with severe alcoholic hepatitis treated with steroids: early response to therapy is the key factor.
        Gastroenterology. 2009; 137: 541-548
        • Philippe M.
        • Christophe M.
        • Didier S.
        • et al.
        Early Liver Transplantation for Severe Alcoholic Hepatitis.
        N Engl J Med. 2011; 365: 1790-1800
        • Raff E.
        • Singal A.K.
        Optimal management of alcoholic hepatitis.
        Minerva Gastroenterol Dietol. 2014; 60: 15
        • Singal A.K.
        • Salameh H.
        • Singal A.
        • et al.
        Management practices of hepatitis C virus infected alcoholic hepatitis patients: A survey of physicians.
        World J Gastrointest Pharmacol Ther. 2013; 4: 16-22
        • Akriviadis E.
        • Botla R.
        • Briggs W.
        • et al.
        Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: A double-blind, placebo-controlled trial.
        Gastroenterology. 2000; 119: 1637-1648
        • Singh S.
        • Murad M.H.
        • Chandar A.K.
        • et al.
        Comparative Effectiveness of Pharmacological Interventions for Severe Alcoholic Hepatitis: A Systematic Review and Network Meta-analysis.
        Gastroenterology. 2015; 149 (e12): 958-970
        • Thompson J.
        • Jones N.
        • Al-Khafaji A.
        • et al.
        Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial.
        Liver Transpl. 2018; 24: 380-393
        • Singal A.K.
        • Shah V.H.
        Current trials and novel therapeutic targets for alcoholic hepatitis.
        J Hepatol. 2019; 70: 305-313
        • Thanda Han M.A.
        • Pyrsopoulos N.
        Emerging Therapies for Alcoholic Hepatitis.
        Clin Liver Dis. 2021; 25: 603-624
        • Purohit V.
        • Bode J.C.
        • Bode C.
        • et al.
        Alcohol, Intestinal Bacterial Growth, Intestinal Permeability to Endotoxin, and Medical Consequences.
        Alcohol. 2008; 42: 349-361
        • Philips C.A.
        • Pande A.
        • Shasthry S.M.
        • et al.
        Healthy Donor Fecal Microbiota Transplantation in Steroid-Ineligible Severe Alcoholic Hepatitis: A Pilot Study.
        Clin Gastroenterol Hepatol. 2017; 15: 600-602
        • Bajaj J.S.
        • Gavis E.A.
        • Fagan A.
        • et al.
        A Randomized Clinical Trial of Fecal Microbiota Transplant for Alcohol Use Disorder.
        Hepatology. 2021; 73: 1688-1700
        • Philips C.A.
        • Ahamed R.
        • Rajesh S.
        • et al.
        Long-term Outcomes of Stool Transplant in Alcohol-associated Hepatitis—Analysis of Clinical Outcomes, Relapse, Gut Microbiota and Comparisons with Standard Care.
        J Clin Exp Hepatol. 2022; 12: 1124-1132
        • Szabo G.
        • Mitchell M.
        • McClain C.J.
        • et al.
        IL-1 receptor antagonist plus pentoxifylline and zinc for severe alcohol-associated hepatitis.
        Hepatology. 2022; 76: 1058-1068
      1. Gawrieh S, Dasarathy S, Tu W, et al. Anakinra plus Zinc versus Prednisone for Treatment of Severe Alcohol-Associated Hepatitis: A Randomized Controlled Trial. Poster presented at: The Liver Meeting. November 4-8, 2012; Washington D.C.

        • Hassanein T.
        • Stein L.
        • Flamm S.
        Safety and Efficacy of DUR-928: A Potential New Therapy for Acute Alcoholic Hepatitis.
        Hepatology. 2019; 70: 1483A-1484A
        • Nguyen-Khac E.
        • Thevenot T.
        • Piquet M.A.
        • et al.
        Glucocorticoids plus N -Acetylcysteine in Severe Alcoholic Hepatitis.
        N Engl J Med. 2011; 365: 1781-1789
        • Higuera-de la Tijera F.
        • Servín-Caamaño A.I.
        • Serralde-Zúñiga A.E.
        • et al.
        Metadoxine improves the three- and six-month survival rates in patients with severe alcoholic hepatitis.
        World J Gastroenterol. 2015; 21: 4975-4985
        • Brand S.
        • Dambacher J.
        • Beigel F.
        • et al.
        IL-22-mediated liver cell regeneration is abrogated by SOCS-1/3 overexpression in vitro.
        Am J Physiology-Gastrointestinal Liver Physiol. 2007; 292: G1019-G1028
        • Arab J.P.
        • Sehrawat T.S.
        • Simonetto D.A.
        • et al.
        An open label, dose escalation study to assess the safety and efficacy of il-22 agonist f-652 in patients with alcoholic hepatitis.
        Hepatology. 2020; 72: 441-453
        • Marot A.
        • Singal A.K.
        • Moreno C.
        • et al.
        Granulocyte colony-stimulating factor for alcoholic hepatitis: A systematic review and meta-analysis of randomised controlled trials.
        JHEP Rep. 2020; 2: 100139
        • Lucey M.R.
        • Brown K.A.
        • Everson G.T.
        • et al.
        Minimal criteria for placement of adults on the liver transplant waiting list: A report of a national conference organized by the American Society of Transplant Physicians and the American Association for the Study of Liver Diseases.
        Liver Transplant Surg. 1997; 3: 628-637
        • Everhart J.E.
        • Beresford T.P.
        Liver transplantation for alcoholic liver disease: A survey of transplantation programs in the United States.
        Liver Transplant Surg. 1997; 3: 220-226
        • Jauhar S.
        • Talwalkar J.A.
        • Schneekloth T.
        • et al.
        Analysis of factors that predict alcohol relapse following liver transplantation.
        Liver Transplant. 2004; 10: 408-411
      2. Are preoperative patterns of alcohol consumption predictive of relapse after liver transplantation for alcoholic liver disease?.
        (Available at:)
        doi:10.1111/j.1432-2277.2005.00208.x
        (Accessed November 20, 2022)
        • Mccallum S.
        • Masterton G.
        Liver transplantation for alcoholic liver disease: a systematic review of psychosocial selection criteria.
        Alcohol Alcohol. 2006; 41: 358-363
        • Lim J.
        • Curry M.P.
        • Sundaram V.
        Risk factors and outcomes associated with alcohol relapse after liver transplantation.
        World J Hepatol. 2017; 9: 771-780
        • Lee B.P.
        • Mehta N.
        • Platt L.
        • et al.
        Outcomes of Early Liver Transplantation for Patients With Severe Alcoholic Hepatitis.
        Gastroenterology. 2018; 155: 422-430.e1
        • Lee B.P.
        • Chen P.H.
        • Haugen C.
        • et al.
        Three-year Results of a Pilot Program in Early Liver Transplantation for Severe Alcoholic Hepatitis.
        Ann Surg. 2017; 265: 20-29
        • Carrique L.
        • Quance J.
        • Tan A.
        • et al.
        Results of Early Transplantation for Alcohol-Related Cirrhosis: Integrated Addiction Treatment With Low Rate of Relapse.
        Gastroenterology. 2021; 161 (e2): 1896-1906
        • Herrick-Reynolds K.M.
        • Punchhi G.
        • Greenberg R.S.
        • et al.
        Evaluation of Early vs Standard Liver Transplant for Alcohol-Associated Liver Disease.
        JAMA Surg. 2021; 156: 1026-1034
        • Marot A.
        • Dubois M.
        • Trépo E.
        • et al.
        Liver transplantation for alcoholic hepatitis: A systematic review with meta-analysis.
        PLoS One. 2018; 13: e0190823
        • Mellinger J.L.
        • Volk M.L.
        Transplantation for Alcohol-related Liver Disease: Is It Fair?.
        Alcohol Alcohol. 2018; 53: 173-177
        • Glannon W.
        Responsibility and Priority in Liver Transplantation.
        Camb Q Healthc Ethics. 2009; 18: 23-35
        • Bangaru S.
        • Pedersen M.R.
        • MacConmara M.P.
        • et al.
        Survey of Liver Transplantation Practices for Severe Acute Alcoholic Hepatitis: Survey of Liver Transplantation.
        Liver Transpl. 2018; 24: 1357-1362
        • Cotter T.G.
        • Sandıkçı B.
        • Paul S.
        • et al.
        Liver transplantation for alcoholic hepatitis in the United States: Excellent outcomes with profound temporal and geographic variation in frequency.
        Am J Transpl. 2021; 21: 1039-1055
        • Bittermann T.
        • Mahmud N.
        • Weinberg E.M.
        • et al.
        Rising Trend in Waitlisting for Alcoholic Hepatitis With More Favorable Outcomes Than Other High Model for End-stage Liver Disease in the Current Era.
        Transplantation. 2022; 106: 1401-1410
        • Altamirano J.
        • López-Pelayo H.
        • Michelena J.
        • et al.
        Alcohol abstinence in patients surviving an episode of alcoholic hepatitis: Prediction and impact on long-term survival: Altamirano, López-Pelayo, et al.
        Hepatology. 2017; 66: 1842-1853
        • Elfeki M.A.
        • Abdallah M.A.
        • Leggio L.
        • et al.
        Simultaneous management of alcohol use disorder and of liver disease: a systematic review and meta-analysis.
        J Addict Med. 2022; (Publish Ahead of Print)https://doi.org/10.1097/ADM.0000000000001084
        • Evans M.D.
        • Diaz J.
        • Adamusiak A.M.
        • et al.
        Predictors of Survival After Liver Transplantation in Patients With the Highest Acuity (MELD ≥40).
        Ann Surg. 2020; 272: 458-466
        • Louvet A
        • Labreuche J.
        • Artru F.
        • et al.
        Main drivers of outcome differ between short term and long term in severe alcoholic hepatitis: A prospective study.
        Hepatology. 2017; 66: 1464-1473
        • Ayyala D
        • Bottyan T.
        • Tien C.
        • et al.
        Naltrexone for alcohol use disorder: Hepatic safety in patients with and without liver disease.
        Hepaol Commun. 2022; 6: 3433-3442
        • Yamini D.
        • Lee S.H.
        • Avanesyan A.
        • et al.
        Utilization of Baclofen in Maintenance of Alcohol Abstinence in Patients with Alcohol Dependence and Alcoholic Hepatitis with or without Cirrhosis.
        Alcohol Alcohol. 2014; 49: 453-456
        • Reus V.I.
        • Hilty D.M.
        • Pasic J.
        • et al.
        The American Psychiatric Association Practice Guideline for the Pharmacological Treatment of Patients With Alcohol Use Disorder.
        Am J Psychiatry. 2018; 175: 86-90
        • Rogal S.
        • Youk A.
        • Zhang H.
        • et al.
        Impact of Alcohol Use Disorder Treatment on Clinical Outcomes among Patients with Cirrhosis.
        Hepatology. 2020; 71: 2080-2092
        • DiMartini A.F.
        • Leggio L.
        • Singal A.K.
        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
        • Lucey M.R.
        • Singal A.K.
        Integrated Treatment of Alcohol Use Disorder in Patients With Alcohol-Associated Liver Disease: An Evolving Story.
        Hepatology. 2020; 71: 1891-1893
        • Mellinger J.L.
        • Scott Winder G.
        • DeJonckheere M.
        • et al.
        Misconceptions, preferences and barriers to alcohol use disorder treatment in alcohol-related cirrhosis.
        J Substance Abuse Treat. 2018; 91: 20-27