title: Hepatitis C Virus, Insulin Resistance, and Steatosis.
abstract: Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide. Liver steatosis is a common finding in many hepatic and extrahepatic disorders, the most common being metabolic syndrome (MS). Over time, it has been shown that the frequent coexistence of these two conditions is not coincidental, since many epidemiological, clinical, and experimental studies have indicated HCV to be strongly associated with liver steatosis and numerous metabolic derangements. Here, we present an overview of publications that provide clinical evidence of the metabolic effects of HCV and summarize the available data on the pathogenetic mechanisms of this association. It has been shown that HCV infection can induce insulin resistance (IR) in the liver and peripheral tissues through multiple mechanisms. Substantial research has suggested that HCV interferes with insulin signaling both directly and indirectly, inducing the production of several proinflammatory cytokines. HCV replication, assembly, and release from hepatocytes require close interactions with lipid droplets and host lipoproteins. This modulation of lipid metabolism in host cells can induce hepatic steatosis, which is more pronounced in patients with HCV genotype 3. The risk of steatosis depends on several viral factors (including genotype, viral load, and gene mutations) and host features (visceral obesity, type 2 diabetes mellitus, genetic predisposition, medication use, and alcohol consumption). HCV-related IR and steatosis have been shown to have a remarkable clinical impact on the prognosis of HCV infection and quality of life, due to their association with resistance to antiviral therapy, progression of hepatic fibrosis, and development of hepatocellular carcinoma. Finally, HCV-induced IR, oxidative stress, and changes in lipid and iron metabolism lead to glucose intolerance, arterial hypertension, hyperuricemia, and atherosclerosis, resulting in increased cardiovascular mortality.
authors.affiliation: Department of Gastroenterology and Hepatology, Sisters of Charity University Hospital Center, Zagreb, Croatia.
authors.forename: Dominik
authors.initials: D
authors.lastname: Kralj
authors.affiliation: Department of Gastroenterology and Hepatology, Sisters of Charity University Hospital Center, Zagreb, Croatia.
authors.forename: Lucija
authors.initials: L
authors.lastname: Virović Jukić
authors.affiliation: Department of Gastroenterology and Hepatology, Sisters of Charity University Hospital Center, Zagreb, Croatia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Stojsavljević
authors.affiliation: Department of Gastroenterology and Hepatology, Sisters of Charity University Hospital Center, Zagreb, Croatia.
authors.forename: Marko
authors.initials: M
authors.lastname: Duvnjak
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Osijek, Osijek, Croatia.
authors.forename: Martina
authors.initials: M
authors.lastname: Smolić
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Osijek, Department of Endocrinology and metabolism disorders, University Hospital Center, Osijek, Osijek, Croatia.
authors.forename: Ines Bilić
authors.initials: IB
authors.lastname: Čurčić
keywords: Hepatitis C virus; Insulin resistance; Metabolic syndrome; Steatosis