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Review
, 21 (27), 8293-303

Lipid Dysregulation in Hepatitis C Virus, and Impact of Statin Therapy Upon Clinical Outcomes

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Review

Lipid Dysregulation in Hepatitis C Virus, and Impact of Statin Therapy Upon Clinical Outcomes

Tracey G Simon et al. World J Gastroenterol.

Abstract

The hepatitis C virus (HCV) is one of the most common causes of chronic liver disease and the leading indication for liver transplantation worldwide. Every aspect of the HCV life cycle is closely tied to human lipid metabolism. The virus circulates as a lipid-rich particle, utilizing lipoprotein cell receptors to gain entry into the hepatocyte. It has also been shown to upregulate lipid biosynthesis and impair lipid degradation, resulting in significant intracellular lipid accumulation and circulating hypocholesterolemia. Patients with chronic hepatitis C (CHC) are at increased risk of hepatic steatosis, fibrosis, and cardiovascular disease including accelerated atherosclerosis. HMG CoA Reductase inhibitors, or statins, have been shown to play an important role in the modulation of hepatic steatosis and fibrosis, and recent attention has focused upon their potential therapeutic role in CHC. This article reviews the hepatitis C viral life cycle as it impacts host lipoproteins and lipid metabolism. It then describes the pathogenesis of HCV-related hepatic steatosis, hypocholesterolemia and atherosclerosis, and finally describes the promising anti-viral and anti-fibrotic effects of statins, for the treatment of CHC.

Keywords: Cholesterol; Cirrhosis; Fibrosis; Hepatitis C virus; Lipid profiles; Statin.

Figures

Figure 1
Figure 1
Hepatitis C virus viral life cycle. Hepatitis C virus (HCV) entry into human hepatocytes is a complex, multi-step process that takes place at the basolateral region of polarized hepatocytes. It begins when the viral particle binds surface glycosaminoglycans (GAGs) and the low-density lipoprotein receptor (LDLR) via apolipoprotein E. This is followed by a complex series of interactions mediated by cellular factors including scavenger receptor class B type I (SR-BI), the tetraspanin CD81, claudin-1 (CLDN1), occludin (OCLN), the Niemann-Pick C1-like 1 (NPC1L1) receptor, as well as receptor tyrosine kinases (RTKs) that promote CD81-CLDN1 association and membrane fusion. The HCV particle is then internalized into the hepatocyte by clathrin-mediated endocytosis. This figure is reproduced with permission from the original article, published in Journal of Hepatology, Vol 57, Issue 1, by Lupberger J, Felmlee J and Baumert TF. Cholesterol Uptake and Hepatitis C virus entry, page 215-217, Copyright Elsevier, 2012.
Figure 2
Figure 2
Hepatitis C virus-mediated perturbations in cholesterol metabolism. HCV: Hepatitis C virus; ROS: Reactive oxygen species; VLDL: Very low-density lipoprotein.

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