title: Alcoholic liver disease: pathogenesis, management, and novel targets for therapy.
abstract: Alcohol use is a leading cause of preventable morbidity and mortality worldwide, with much of its negative impact as the result of alcoholic liver disease (ALD). ALD is a broad term that encompasses a spectrum of phenotypes ranging from simple steatosis to steatohepatitis, progressive fibrosis, cirrhosis, and hepatocellular carcinoma. The mechanisms underlying the development of these different disease stages are incompletely understood. Standard treatment of ALD, which includes abstinence, nutritional support, and corticosteroids, has not changed in the last 40 years despite continued poor outcomes. Novel therapies are therefore urgently needed. The development of such therapies has been hindered by inadequate resources for research and unsuitable animal models. However, recent developments in translational research have allowed for identification of new potential targets for therapy. These targets include: (i) CXC chemokines, (ii) IL-22/STAT3, (iii) TNF receptor superfamily, (iv) osteopontin, (v) gut microbiota and lipopolysaccharide (LPS), (vi) endocannabinoids, and (vii) inflammasomes. We review the natural history, risk factors, pathogenesis, and current treatments for ALD. We further discuss the findings of recent translational studies and potential therapeutic targets.
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ramon_bataller@med.unc.edu
authors.forename: Eric S
authors.initials: ES
authors.lastname: Orman
authors.forename: Gemma
authors.initials: G
authors.lastname: Odena
authors.forename: Ramon
authors.initials: R
authors.lastname: Bataller
mesh_terms: D000818:Animals; D019743:Chemokines, CXC; D003978:Diazomethane / Q000031:analogs & derivatives; D004195:Disease Models, Animal; D063388:Endocannabinoids; D005227:Fatty Acids; D006801:Humans; D058847:Inflammasomes; D007378:Interleukins; D007422:Intestines / Q000382:microbiology; D008070:Lipopolysaccharides; D008108:Liver Diseases, Alcoholic / Q000209:etiology* / Q000235:genetics / Q000628:therapy*; D058990:Molecular Targeted Therapy; D053495:Osteopontin; D018124:Receptors, Tumor Necrosis Factor; D050796:STAT3 Transcription Factor; D057170:Translational Research, Biomedical; D000097043:Interleukin-22
chemical_list: D019743:Chemokines, CXC; D003978:Diazomethane; D063388:Endocannabinoids; D005227:Fatty Acids; D058847:Inflammasomes; D007378:Interleukins; D008070:Lipopolysaccharides; D053495:Osteopontin; D018124:Receptors, Tumor Necrosis Factor; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22; C503508:9-(((2-iodo-4-((trifluoromethyl)-3H-diazirin-3-yl)benzyl)oxy)carbonyl)nonanoic acid
keywords: alcoholic liver diseases; fibrosis; inflammation; translational research