Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis

Hepatology. 2010 Nov;52(5):1836-46. doi: 10.1002/hep.24001.


Whereas in most cases a fatty liver remains free of inflammation, 10%-20% of patients who have fatty liver develop inflammation and fibrosis (nonalcoholic steatohepatitis [NASH]). Inflammation may precede steatosis in certain instances. Therefore, NASH could reflect a disease where inflammation is followed by steatosis. In contrast, NASH subsequent to simple steatosis may be the consequence of a failure of antilipotoxic protection. In both situations, many parallel hits derived from the gut and/or the adipose tissue may promote liver inflammation. Endoplasmic reticulum stress and related signaling networks, (adipo)cytokines, and innate immunity are emerging as central pathways that regulate key features of NASH.

Publication types

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

MeSH terms

  • Animals
  • Diet
  • Disease Progression
  • Fatty Liver / chemically induced
  • Fatty Liver / etiology
  • Fatty Liver / physiopathology*
  • Humans
  • Inflammation / complications
  • Inflammation / physiopathology*
  • Interleukin-5 / adverse effects
  • Interleukin-5 / genetics
  • Leptin / adverse effects
  • Leptin / physiology
  • Metabolic Diseases / complications
  • Metabolic Diseases / etiology
  • Metabolic Diseases / physiopathology
  • Models, Biological
  • Obesity / complications
  • Trans Fatty Acids / adverse effects
  • Tumor Necrosis Factor-alpha / adverse effects
  • Tumor Necrosis Factor-alpha / genetics


  • Interleukin-5
  • Leptin
  • Trans Fatty Acids
  • Tumor Necrosis Factor-alpha