Non-alcoholic Steatohepatitis Pathogenesis: Sublethal Hepatocyte Injury As a Driver of Liver Inflammation

Overview

Journal Gut

Specialty Gastroenterology

Date 2018 Jan 26

PMID 29367207

Citations 124

Authors

Samar H Ibrahim

Petra Hirsova

Gregory J Gores

Affiliations

Soon will be listed here.

Abstract

A subset of patients with non-alcoholic fatty liver disease develop an inflammatory condition, termed non-alcoholic steatohepatitis (NASH). NASH is characterised by hepatocellular injury, innate immune cell-mediated inflammation and progressive liver fibrosis. The mechanisms whereby hepatic inflammation occurs in NASH remain incompletely understood, but appear to be linked to the proinflammatory microenvironment created by toxic lipid-induced hepatocyte injury, termed lipotoxicity. In this review, we discuss the signalling pathways induced by sublethal hepatocyte lipid overload that contribute to the pathogenesis of NASH. Furthermore, we will review the role of proinflammatory, proangiogenic and profibrotic hepatocyte-derived extracellular vesicles as disease biomarkers and pathogenic mediators during lipotoxicity. We also review the potential therapeutic strategies to block the feed-forward loop between sublethal hepatocyte injury and liver inflammation.

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