Hepatic non-parenchymal cells: Master regulators of alcoholic liver disease?

World J Gastroenterol. 2016 Jan 28;22(4):1348-56. doi: 10.3748/wjg.v22.i4.1348.


Chronic alcohol consumption is one of the most common causes of the progression of alcoholic liver disease (ALD). In the past, alcohol-mediated hepatocyte injury was assumed to be a significantly major cause of ALD. However, a huge number of recent and brilliant studies have demonstrated that hepatic non-parenchymal cells including Kupffer cells, hepatic stellate cells, liver sinusoidal endothelial cells and diverse types of lymphocytes play crucial roles in the pathogenesis of ALD by producing inflammatory mediators such as cytokines, oxidative stress, microRNA, and lipid-originated metabolites (retinoic acid and endocannabinoids) or by directly interacting with parenchymal cells (hepatocytes). Therefore, understanding the comprehensive roles of hepatic non-parenchymal cells during the development of ALD will provide new integrative directions for the treatment of ALD. This review will address the roles of non-parenchymal cells in alcoholic steatosis, inflammation, and liver fibrosis and might help us to discover possible therapeutic targets and treatments involving modulating the non-parenchymal cells in ALD.

Keywords: Alcoholic liver disease; Endocannabinoid; NADPH oxidase; Reactive oxygen stress.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / therapeutic use
  • Hepatic Stellate Cells / drug effects
  • Hepatic Stellate Cells / immunology
  • Hepatic Stellate Cells / metabolism*
  • Hepatic Stellate Cells / pathology
  • Humans
  • Inflammation Mediators / metabolism
  • Kupffer Cells / drug effects
  • Kupffer Cells / immunology
  • Kupffer Cells / metabolism*
  • Kupffer Cells / pathology
  • Liver / drug effects
  • Liver / immunology
  • Liver / metabolism*
  • Liver / pathology
  • Liver Diseases, Alcoholic / drug therapy
  • Liver Diseases, Alcoholic / immunology
  • Liver Diseases, Alcoholic / metabolism*
  • Liver Diseases, Alcoholic / pathology
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism
  • Signal Transduction


  • Anti-Inflammatory Agents
  • Antioxidants
  • Inflammation Mediators
  • Reactive Oxygen Species