Pathogenesis of alcoholic liver disease

Gavin E. Arteel, David Crabb

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

Alcoholic liver disease (ALD) is a spectrum of injury to the liver that includes steatosis, inflammation, fibrosis, and cirrhosis. Hepatic steatosis is the first manifestation of excessive drinking and, while reversible, signifies the presence of ongoing metabolic stress on the liver which underlies the more serious stages of ALD. Lipid accumulation results from widespread disturbances in the handling of fat by the body (adipose dysfunction), increased de novo synthesis, and impaired fatty acid oxidation and export as VLDL. These metabolic disturbances are driven by oxidative and ER stress, generation of ceramide, abnormal homocysteine metabolism, activation of the innate immune response, and dysfunctional transcriptional control of lipid-metabolizing pathways. The alcoholic fatty liver probably is always mildly inflamed and sensitive to necrosis, apoptosis, and necroptosis when additional stresses are imposed. The most important of these is the exposure to abnormal levels of lipopolysaccharide reaching the liver from an abnormally permeably gut. Inflammation involves particularly innate immune mechanisms, in particular the release of TNFa by the Kupffer cells, and is a prime driver of fibrosis mediated by hepatic stellate cells (HSC). Unconventional contributors to ALD include the complement system, coagulation pathway, and osteopontin. Improved therapies will need to take into consideration the numerous metabolic and signaling pathways deranged in heavy drinkers.

Original languageEnglish (US)
Title of host publicationAlcoholic and Non-Alcoholic Fatty Liver Disease: Bench to Bedside
PublisherSpringer International Publishing
Pages41-69
Number of pages29
ISBN (Electronic)9783319205380
ISBN (Print)9783319205373
DOIs
StatePublished - Jan 1 2015

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Keywords

  • Apoptosis
  • Cytokines
  • Fibrosis
  • Inflammation
  • Innate immunity
  • Lipopolysaccharide
  • Necroptosis
  • Oxidative stress
  • Steatosis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Arteel, G. E., & Crabb, D. (2015). Pathogenesis of alcoholic liver disease. In Alcoholic and Non-Alcoholic Fatty Liver Disease: Bench to Bedside (pp. 41-69). Springer International Publishing. https://doi.org/10.1007/978-3-319-20538-0_3