Linking Pathogenic Mechanisms of Alcoholic Liver Disease With Clinical Phenotypes

Gastroenterology. 2016 Jun;150(8):1756-68. doi: 10.1053/j.gastro.2016.02.035. Epub 2016 Feb 23.

Abstract

Alcoholic liver disease (ALD) develops in approximately 20% of alcoholic patients, with a higher prevalence in females. ALD progression is marked by fatty liver and hepatocyte necrosis, as well as apoptosis, inflammation, regenerating nodules, fibrosis, and cirrhosis.(1) ALD develops via a complex process involving parenchymal and nonparenchymal cells, as well as recruitment of other cell types to the liver in response to damage and inflammation. Hepatocytes are damaged by ethanol, via generation of reactive oxygen species and induction of endoplasmic reticulum stress and mitochondrial dysfunction. Hepatocyte cell death via apoptosis and necrosis are markers of ethanol-induced liver injury. We review the mechanisms by which alcohol injures hepatocytes and the response of hepatic sinusoidal cells to alcohol-induced injury. We also discuss how recent insights into the pathogenesis of ALD will affect the treatment and management of patients.

Keywords: Alcoholic Hepatitis; Alcoholic Liver Disease; Hepatic Stellate Cell.

Publication types

  • Review

MeSH terms

  • Apoptosis / drug effects
  • Endoplasmic Reticulum Stress / drug effects
  • Ethanol / adverse effects*
  • Female
  • Hepatocytes / drug effects*
  • Humans
  • Liver / cytology
  • Liver / physiopathology
  • Liver Diseases, Alcoholic / etiology*
  • Liver Diseases, Alcoholic / physiopathology
  • Male
  • Phenotype
  • Reactive Oxygen Species / chemical synthesis

Substances

  • Reactive Oxygen Species
  • Ethanol