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

Authors

  • Herbert Tilg,

    Corresponding author
    1. Christian Doppler Research Laboratory for Gut Inflammation, Medical University Innsbruck, Innsbruck, Austria
    • Christian Doppler Research Laboratory for Gut Inflammation, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria
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    • fax: +43 512 504 67 23374

  • Alexander R. Moschen

    1. Christian Doppler Research Laboratory for Gut Inflammation, Medical University Innsbruck, Innsbruck, Austria
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  • Potential conflict of interest: Nothing to report.

Abstract

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. (HEPATOLOGY 2010;52:1836-1846)

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