New advances in molecular mechanisms and emerging therapeutic targets in alcoholic liver diseases

World J Gastroenterol. 2014 Sep 28;20(36):12908-33. doi: 10.3748/wjg.v20.i36.12908.

Abstract

Alcoholic liver disease is a major health problem in the United States and worldwide. Chronic alcohol consumption can cause steatosis, inflammation, fibrosis, cirrhosis and even liver cancer. Significant progress has been made to understand key events and molecular players for the onset and progression of alcoholic liver disease from both experimental and clinical alcohol studies. No successful treatments are currently available for treating alcoholic liver disease; therefore, development of novel pathophysiological-targeted therapies is urgently needed. This review summarizes the recent progress on animal models used to study alcoholic liver disease and the detrimental factors that contribute to alcoholic liver disease pathogenesis including miRNAs, S-adenosylmethionine, Zinc deficiency, cytosolic lipin-1β, IRF3-mediated apoptosis, RIP3-mediated necrosis and hepcidin. In addition, we summarize emerging adaptive protective effects induced by alcohol to attenuate alcohol-induced liver pathogenesis including FoxO3, IL-22, autophagy and nuclear lipin-1α.

Keywords: Alcoholic liver disease; Autophagy; Fatty liver; FoxO3; IL-22; Lipin-1; RIP3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Drug Design*
  • Genetic Predisposition to Disease
  • Humans
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases, Alcoholic / diagnosis
  • Liver Diseases, Alcoholic / drug therapy*
  • Liver Diseases, Alcoholic / genetics
  • Liver Diseases, Alcoholic / metabolism
  • Molecular Targeted Therapy*
  • Phenotype
  • Protective Factors
  • Risk Factors
  • Signal Transduction / drug effects
  • Treatment Outcome