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Pathogenesis and natural course of hepatic steatosis and insulin resistance in patients with hepatitis C

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Abstract

Steatosis is a common histologic feature in chronic hepatitis C virus (HCV) infection. Viral steatosis, seen in genotype 3a, is strongly related to viral replication; metabolic steatosis, reported in genotype 1, has been associated with obesity, type 2 diabetes, and metabolic syndrome. HCV promotes lipid accumulation in hepatocytes, increasing free fatty acid synthesis and decreasing lipid oxidation and secretion. Several amino acid changes in core protein have been strongly related to steatosis development; for example, the Y164F change has been related to greater cumulative lipid droplets. Steatosis-induced HCV seems to act as an organelle supporting stable viral replication. HCV proteins promote insulin receptor substrate-1 (IRS-1) degradation by several mechanisms, including oxidative stress, peroxisome proliferator-activated receptor (PPAR) downregulation, and enhancement of tumor necrosis factor production in a genotype-dependent manner. In genotype 1, IRS-1 degradation was induced by mammalian target of rapamycin and in genotype 3, by suppressor of cytokine signaling-7 and PPAR. Steatosis and insulin resistance have been associated with fibrosis progression.

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  1. Unit for the Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Ctra de Cadiz s/n, Sevilla, 41014, Spain

    Manuel Romero-Gómez

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Correspondence to Manuel Romero-Gómez.

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Romero-Gómez, M. Pathogenesis and natural course of hepatic steatosis and insulin resistance in patients with hepatitis C. Curr hepatitis rep 7, 113–119 (2008). https://doi.org/10.1007/s11901-008-0024-0

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