Hepatitis C Virus-Lipid Interplay: Pathogenesis and Clinical Impact

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.

Tendon Disorders in Chronic Liver Disease: A Retrospective Cohort Study in Taiwan

“…In liver disease, NAFLD was found to be caused by metabolic dysfunction; conversely, overproduction of triglycerides and glucose in the fatty liver increased metabolic syndrome [ 9 ]. Similar vicious cycles occur in other liver diseases, such as alcoholic liver disease [ 10 ] and chronic hepatitis C [ 11 ].…”

“…It defines the disease with evidence of hepatosteatosis using any one of three criteria: obesity, type 2 diabetes mellitus, and metabolic dysregulation. Aside from NAFLD [ 8 , 9 ], metabolic dysfunction is commonly found in other liver diseases, such as alcoholic liver disease [ 10 ] and chronic hepatitis C [ 11 ]. As time passes, liver disease can progress to liver cirrhosis, an end-stage liver conditions with permanent scarring and damage to the liver.…”

Thyroid Hormonal, Lipidic and Inflammatory Profiles in Patients with Hepatic Encephalopathy

“…Another reason for the insufficiently significant results could be represented by the conditions that must be observed by the patients before the sample collection, impossible to achieve in most cases. The patients included in the study group were hospitalized after exclusively appearing in the Emergency Unit, and the samples for the lipid profile were collected in most cases on the first day of hospital admission [26].…”

Chronic Hepatitis C Virus Infection, Extrahepatic Disease and the Impact of New Direct-Acting Antivirals

“…Regarding other effects, the current evidence has shown significant metabolic alterations in chronic HCV infection. For instance, a prevalence is estimated of about 55.54% for liver steatosis in patients with HCV infection, especially when infected with genotype 3, increasing fibrosis progression with pre-existing liver steatosis but also as a bad response to antiviral therapy [ 30 , 31 ]. HCV infection disrupts lipoprotein homeostasis, including the low-density lipoprotein cholesterol (VLDL)-releasing pathway.…”

“…HCV infection disrupts lipoprotein homeostasis, including the low-density lipoprotein cholesterol (VLDL)-releasing pathway. In fact, viral proteins like NS4B and NS5A induce the formation of lipid droplets (LDs) by altering the ER structure through cellular lipid lipase activation [ 30 , 32 ]. Furthermore, lipoviral particles are incorporated into LDs in the VLDL within the ER [ 31 , 32 ].…”