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Review
. 2023 Jan 19;11(2):271.
doi: 10.3390/biomedicines11020271.

Hepatitis C Virus-Lipid Interplay: Pathogenesis and Clinical Impact

Wesal Elgretli  1 , Tianyan Chen  2 , Nadine Kronfli  3   4 , Giada Sebastiani  1   2   3
Affiliations
Review

Hepatitis C Virus-Lipid Interplay: Pathogenesis and Clinical Impact

Wesal Elgretli et al. Biomedicines. .

Abstract

Hepatitis C virus (HCV) infection represents the major cause of chronic liver disease, leading to a wide range of hepatic diseases, including cirrhosis and hepatocellular carcinoma. It is the leading indication for liver transplantation worldwide. In addition, there is a growing body of evidence concerning the role of HCV in extrahepatic manifestations, including immune-related disorders and metabolic abnormalities, such as insulin resistance and steatosis. HCV depends on its host cells to propagate successfully, and every aspect of the HCV life cycle is closely related to human lipid metabolism. The virus circulates as a lipid-rich particle, entering the hepatocyte via lipoprotein cell receptors. It has also been shown to upregulate lipid biosynthesis and impair lipid degradation, resulting in significant intracellular lipid accumulation (steatosis) and circulating hypocholesterolemia. Patients with chronic HCV are at increased risk for hepatic steatosis, dyslipidemia, and cardiovascular disease, including accelerated atherosclerosis. This review aims to describe different aspects of the HCV viral life cycle as it impacts host lipoproteins and lipid metabolism. It then discusses the mechanisms of HCV-related hepatic steatosis, hypocholesterolemia, and accelerated atherosclerosis.

Keywords: atherosclerosis; cholesterol; hepatitis C; lipid metabolism; steatosis.

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Conflict of interest statement

GS has acted as a speaker for Merck, Gilead, Abbvie, Novonordisk, Novartis and Pfizer, served as an advisory board member for Pfizer, Merck, Novonordisk, Gilead and Intercept, and has received unrestricted research funding from Theratec. NK reports research funding from Gilead Sciences, advisory fees from Gilead Sciences, ViiV Healthcare, Merck and Abbvie, and speaker fees from Gilead Sciences and Merck. TC and WE declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic presentation of HCV genome and polyprotein precursor. The HCV genome encodes a polyprotein of about 3000 amino acids and comprises an open reading frame flanked by 5′ and 3′ untranslated regions (UTRs). Following translation, the core, E1, and E2 proteins, as well as p7, are separated from the polyprotein by cellular peptidase. NS2’s protease activity separates NS2 from NS3, whereas the viral replication components (NS3-NS5B) are separated by the NS3-4A protease. C: core protein; E1 and E2: envelope glycoprotein E1 and E2; NS: nonstructural.
Figure 2
Figure 2
Hepatitis C virus Lipoviroparticles (LVP). The highly infectious HCV particle corresponds to a hybrid particle composed of VLDL or LDL components and viral components named LVP. VLDL: very-low density lipoproteins; LDL: low-density lipoprotein.
Figure 3
Figure 3
HCV induced alterations in lipid metabolism and steatosis. IR: Insulin resistance; PPAR-α: Peroxisome proliferator-activated receptor-α; ROS: Reactive oxygen species; MTP: Microsomal triglyceride transfer protein; VLDL: very-low density lipoproteins.
Figure 4
Figure 4
Direct and indirect pathogenic mechanisms responsible for the development of atherosclerosis in chronic hepatitis C infection. HCV: Hepatitis C virus; IR: Insulin resistance; TNF-α: Tumor necrosis factor-α; IL1B: interleukin-B1.
See this image and copyright information in PMC

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