{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T16:30:25Z","timestamp":1778430625999,"version":"3.51.4"},"reference-count":54,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2015,11,2]],"date-time":"2015-11-02T00:00:00Z","timestamp":1446422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK083283"],"award-info":[{"award-number":["DK083283"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["01BX002418"],"award-info":[{"award-number":["01BX002418"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Alcoholic liver disease is one of the most prevalent liver diseases worldwide,  and a major cause of morbidity and mortality. Alcoholic hepatitis is a severe form of liver injury in patients with alcohol abuse, can present as an acute on chronic liver failure associated with a rapid decline in liver synthetic function, and consequent increase in mortality. Despite therapy, about 30%\u201350% of patients with severe alcoholic hepatitis eventually die. The pathogenic pathways that lead to the development of alcoholic hepatitis are complex and involve oxidative stress, gut dysbiosis, and dysregulation of the innate and adaptive immune system with injury to the parenchymal cells and activation of hepatic stellate cells. As accepted treatment approaches are currently limited, a better understanding of the pathophysiology would be required to generate new approaches that improve outcomes. This review focuses on recent advances in the diagnosis, pathogenesis of alcoholic hepatitis and novel treatment strategies.<\/jats:p>","DOI":"10.3390\/biom5042978","type":"journal-article","created":{"date-parts":[[2015,11,2]],"date-time":"2015-11-02T10:45:06Z","timestamp":1446461106000},"page":"2978-2986","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Update on Alcoholic Hepatitis"],"prefix":"10.3390","volume":"5","author":[{"given":"Natalie","family":"Torok","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, UC Davis Medical Center, Sacramento, CA 95817, USA"},{"name":"Department of Internal Medicine, Northern California VA System, Mather, CA 95655, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1002\/hep.22010","article-title":"Determinants of alcohol use and abuse: Impact of quantity and frequency patterns on liver disease","volume":"46","author":"Zakhari","year":"2007","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1016\/S0140-6736(09)60746-7","article-title":"Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders","volume":"373","author":"Rehm","year":"2009","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"774","DOI":"10.15288\/jsad.2011.72.774","article-title":"Hospitalizations for alcohol and drug overdoses in young adults ages 18\u201324 in the United States, 1999\u20132008: Results from the nationwide inpatient sample","volume":"72","author":"White","year":"2011","journal-title":"J. Stud. Alcohol. Drugs"},{"key":"ref_4","first-page":"515","article-title":"Natural history of alcoholic hepatitis. II. The long-term prognosis","volume":"56","author":"Alexander","year":"1971","journal-title":"Am. J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0168-8278(02)00413-0","article-title":"A comparison of fibrosis progression in chronic liver diseases","volume":"38","author":"Poynard","year":"2003","journal-title":"J. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1111\/j.1365-2036.2007.03302.x","article-title":"Fibrosis progression occurs in a subgroup of heavy drinkers with typical histological features","volume":"25","author":"Mathurin","year":"2007","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1002\/hep.24017","article-title":"Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians","volume":"53","author":"Stickel","year":"2011","journal-title":"Hepatology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/ng.488","article-title":"Variant in PNPLA3 is associated with alcoholic liver disease","volume":"42","author":"Tian","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Salameh, H., Raff, E., Erwin, A., Seth, D., Nischalke, H.D., Falleti, E., Burza, M.A., Leathert, J., Romeo, S., and Molinaro, A. (2015). PNPLA3 gene polymorphism is associated with predisposition to and severity of alcoholic liver disease. Am. J. Gastroenterol.","DOI":"10.1038\/ajg.2015.181"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Salameh, H., Raff, E., Erwin, A., Seth, D., Nischalke, H.D., Falleti, E., Burza, M.A., Leathert, J., Romeo, S., and Molinaro, A. (2015). Corrigendum: PNPLA3 Gene polymorphism is associated with predisposition to and severity of alcoholic liver disease. Am. J. Gastroenterol.","DOI":"10.1038\/ajg.2015.181"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S61","DOI":"10.1016\/j.pan.2015.03.003","article-title":"Metabolic reprogramming and cell fate regulation in alcoholic liver disease","volume":"15","author":"Tsukamoto","year":"2015","journal-title":"Pancreatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2758","DOI":"10.1056\/NEJMra0805786","article-title":"Alcoholic hepatitis","volume":"360","author":"Lucey","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1111\/j.1530-0277.1993.tb05673.x","article-title":"Alcohol consumption and alcoholic liver disease: Evidence of a threshold level of effects of ethanol","volume":"17","author":"Savolainen","year":"1993","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.gastrohep.2014.02.001","article-title":"Alcoholic hepatitis: Prognosis and treatment","volume":"37","author":"Casanova","year":"2014","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1053\/j.gastro.2014.01.018","article-title":"A histologic scoring system for prognosis of patients with alcoholic hepatitis","volume":"146","author":"Altamirano","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1053\/j.gastro.2006.08.020","article-title":"Utility of a new model to diagnose an alcohol basis for steatohepatitis","volume":"131","author":"Dunn","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/hep.510250120","article-title":"Excess weight risk factor for alcoholic liver disease","volume":"25","author":"Naveau","year":"1997","journal-title":"Hepatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"685","DOI":"10.7326\/0003-4819-110-9-685","article-title":"Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial","volume":"110","author":"Carithers","year":"1989","journal-title":"Ann. Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1002\/hep.20503","article-title":"MELD accurately predicts mortality in patients with alcoholic hepatitis","volume":"41","author":"Dunn","year":"2005","journal-title":"Hepatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1111\/j.1572-0241.2008.02104.x","article-title":"A new scoring system for prognostic stratification of patients with alcoholic hepatitis","volume":"103","author":"Dominguez","year":"2008","journal-title":"Am. J. Gastroenterol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1002\/hep.21607","article-title":"The Lille model: A new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids","volume":"45","author":"Louvet","year":"2007","journal-title":"Hepatology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S39","DOI":"10.1016\/S0168-8278(12)60005-1","article-title":"Management of alcoholic hepatitis","volume":"56","author":"Mathurin","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1002\/hep.27779","article-title":"Systemic inflammatory response and serum lipopolysaccharide levels predict multiple organ failure and death in alcoholic hepatitis","volume":"62","author":"Michelena","year":"2015","journal-title":"Hepatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"G819","DOI":"10.1152\/ajpgi.00041.2014","article-title":"Animals models of gastrointestinal and liver diseases. Animal models of alcohol-induced liver disease: Pathophysiology, translational relevance, and challenges","volume":"306","author":"Mathews","year":"2014","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1002\/hep.26419","article-title":"Chronic plus binge ethanol feeding synergistically induces neutrophil infiltration and liver injury in mice: A critical role for E-selectin","volume":"58","author":"Bertola","year":"2013","journal-title":"Hepatology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/978-1-59745-242-7_17","article-title":"Formation and immunological properties of aldehyde-derived protein adducts following alcohol consumption","volume":"447","author":"Thiele","year":"2008","journal-title":"Methods Mol. Biol."},{"key":"ref_27","first-page":"1103","article-title":"Autoimmune responses against oxidant stress and acetaldehyde-derived epitopes in human alcohol consumers","volume":"24","author":"Viitala","year":"2000","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_28","first-page":"285","article-title":"Dangerous byproducts of alcohol breakdown\u2014Focus on adducts","volume":"27","author":"Tuma","year":"2003","journal-title":"Alcohol. Res. Health"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17756","DOI":"10.3748\/wjg.v20.i47.17756","article-title":"Pathogenesis of alcoholic liver disease: Role of oxidative metabolism","volume":"20","author":"Ceni","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1111\/j.1440-1746.2006.04595.x","article-title":"Cytochrome P450 2E1-dependent oxidant stress and upregulation of anti-oxidant defense in liver cells","volume":"21","author":"Cederbaum","year":"2006","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1111\/j.1440-1746.2006.04650.x","article-title":"Regulation of macrophage activation in alcoholic liver disease","volume":"22","author":"Thakur","year":"2007","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/0741-8329(93)90067-X","article-title":"Mitochondrial glutathione depletion in alcoholic liver disease","volume":"10","author":"Hirano","year":"1993","journal-title":"Alcohol"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1002\/hep.22222","article-title":"Cytochrome P450 2E1 contributes to ethanol-induced fatty liver in mice","volume":"47","author":"Lu","year":"2008","journal-title":"Hepatology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1056\/NEJMoa1101214","article-title":"Glucocorticoids plus N-acetylcysteine in severe alcoholic hepatitis","volume":"365","author":"Thevenot","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/hep.24018","article-title":"Enteric dysbiosis associated with a mouse model of alcoholic liver disease","volume":"53","author":"Yan","year":"2011","journal-title":"Hepatology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1002\/hep.27489","article-title":"Dysbiosis-induced intestinal inflammation activates tumor necrosis factor receptor I and mediates alcoholic liver disease in mice","volume":"61","author":"Chen","year":"2015","journal-title":"Hepatology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"51S","DOI":"10.1111\/j.1530-0277.2001.tb02418.x","article-title":"Kupffer cell sensitization by alcohol involves increased permeability to gut-derived endotoxin","volume":"25","author":"Enomoto","year":"2001","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4737","DOI":"10.4049\/jimmunol.166.7.4737","article-title":"Reduced early alcohol-induced liver injury in CD14-deficient mice","volume":"166","author":"Yin","year":"2001","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Blackmore, L.J., Ryan, J.M., Huang, X., Hussain, M., Triantafyllou, E., Vergis, N., Vijay, G.M., Antoniades, C.G., Thursz, M.R., and Jassem, W. (2015). Acute alcoholic hepatitis and cellular Th1 immune responses to alcohol dehydrogenase. Lancet.","DOI":"10.1016\/S0140-6736(15)60337-3"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1053\/j.gastro.2014.11.041","article-title":"Blockade of PD1 and TIM3 restores innate and adaptive immunity in patients with acute alcoholic hepatitis","volume":"148","author":"Markwick","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1002\/hep.25614","article-title":"Liver progenitor cell markers correlate with liver damage and predict short-term mortality in patients with alcoholic hepatitis","volume":"55","author":"Altamirano","year":"2012","journal-title":"Hepatology"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Dubuquoy, L., Louvet, A., Lassailly, G., Truant, S., Boleslawski, E., Artru, F., Maggiotto, F., Gantier, E., Buob, D., and Leteurtre, E. (2015). Progenitor cell expansion and impaired hepatocyte regeneration in explanted livers from alcoholic hepatitis. Gut.","DOI":"10.1136\/gutjnl-2014-308410"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/S0168-8278(12)61033-2","article-title":"EASL clinical practical guidelines: Management of alcoholic liver disease","volume":"57","author":"Mathurin","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/ajg.2009.593","article-title":"Alcoholic liver disease","volume":"105","author":"Dasarathy","year":"2010","journal-title":"Am. J. Gastroenterol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/S0168-8278(01)00289-6","article-title":"Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis (AH): Individual data analysis of the last three randomized placebo controlled double blind trials of corticosteroids in severe AH","volume":"36","author":"Mathurin","year":"2002","journal-title":"J. Hepatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1053\/gast.2000.20189","article-title":"Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: A double-blind, placebo-controlled trial","volume":"119","author":"Akriviadis","year":"2000","journal-title":"Gastroenterology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1001\/jama.2013.276300","article-title":"Prednisolone with vs. without pentoxifylline and survival of patients with severe alcoholic hepatitis: A randomized clinical trial","volume":"310","author":"Mathurin","year":"2013","journal-title":"JAMA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1056\/NEJMoa1412278","article-title":"Prednisolone or pentoxifylline for alcoholic hepatitis","volume":"372","author":"Thursz","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1002\/hep.23837","article-title":"Interleukin-22 treatment ameliorates alcoholic liver injury in a murine model of chronic-binge ethanol feeding: Role of signal transducer and activator of transcription 3","volume":"52","author":"Ki","year":"2010","journal-title":"Hepatology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1271\/bbb.110061","article-title":"Interleukin-22 protects against acute alcohol-induced hepatotoxicity in mice","volume":"75","author":"Xing","year":"2011","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/cmi.2010.5","article-title":"Th17 cells and their associated cytokines in liver diseases","volume":"7","author":"Lafdil","year":"2010","journal-title":"Cell. Mol. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1002\/hep.26336","article-title":"Therapeutic potential of interleukin 1 inhibitors in the treatment of alcoholic liver disease","volume":"57","author":"Mathews","year":"2013","journal-title":"Hepatology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3476","DOI":"10.1172\/JCI60777","article-title":"IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice","volume":"122","author":"Petrasek","year":"2012","journal-title":"J. Clin Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1056\/NEJMoa1105703","article-title":"Early liver transplantation for severe alcoholic hepatitis","volume":"365","author":"Mathurin","year":"2011","journal-title":"N. Engl. J. Med."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/5\/4\/2978\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:51:18Z","timestamp":1760215878000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/5\/4\/2978"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,2]]},"references-count":54,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2015,12]]}},"alternative-id":["biom5042978"],"URL":"https:\/\/doi.org\/10.3390\/biom5042978","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,2]]}}}