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Chunk #0 — Introduction

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Critical role of cytochrome P450 2E1 (CYP2E1) in the development of high fat-induced non-alcoholic steatohepatitis.
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Nonalcoholic fatty liver disease (NAFLD), a major health burden [1 and references within], is a chronic liver disease characterized by fat accumulation (steatosis). However, a small portion of NAFLD can progress to advanced forms of liver injury such as necro-inflammation, fibrosis, cirrhosis, hepatocellular carcinoma and liver failure. NAFLD with inflammation is called nonalcoholic steatohepatitis (NASH) [2]. The “two-hit” hypothesis [3] described the pathophysiology of NASH. Steatosis (a primary insult) can sensitize the liver to secondary serious insults including reactive oxygen/nitrogen species (ROS/RNS), gut-derived endotoxins, pro-inflammatory cytokines like tumor necrosis factor-alpha (TNFα), resulting in NASH development [1–3].