title: NAFLD and NASH in HCV Infection: Prevalence and Significance in Hepatic and Extrahepatic Manifestations.
abstract: The aim of this paper is to review and up to date the prevalence of hepatitis C virus (HCV)-associated non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) and their significance in both accelerating progression of HCV-related liver disease and development of HCV-associated extrahepatic diseases. The reported mean prevalence of HCV-related NAFLD was 55%, whereas NASH was reported in 4%-10% of cases. HCV genotype 3 directly induces fatty liver deposition, namely "viral steatosis" and it is associated with the highest prevalence and degree of severity, whereas, HCV non-3 genotype infection showed lower prevalence of steatosis, which is associated with metabolic factors and insulin resistance. The host's genetic background predisposes him or her to the development of steatosis. HCV's impairment of lipid and glucose metabolism causes fatty liver accumulation; this seems to be a viral strategy to optimize its life cycle. Irrespective of insulin resistance, HCV-associated NAFLD, in a degree-dependent manner, contributes towards accelerating the liver fibrosis progression and development of hepatocellular carcinoma by inducing liver inflammation and oxidative stress. Furthermore, NAFLD is associated with the presence of metabolic syndrome, type 2 diabetes, and atherosclerosis. In addition, HCV-related "metabolic steatosis" impairs the response rate to interferon-based treatment, whereas it seems that "viral steatosis" may harm the response rate to new oral direct antiviral agents. In conclusion, a high prevalence of NAFLD occurs in HCV infections, which is, at least in part, induced by the virus, and that NAFLD significantly impacts progression of the liver disease, therapeutic response, and some extrahepatic diseases.
authors.affiliation: Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy. luigielio.adinolfi@unina2.it.
authors.forename: Luigi Elio
authors.initials: LE
authors.lastname: Adinolfi
authors.affiliation: Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy. lucarinaldi@hotmail.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Rinaldi
authors.affiliation: Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy. barbara.guerrera@alice.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Guerrera
authors.affiliation: Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy. luciano.restivo@gmail.it.
authors.forename: Luciano
authors.initials: L
authors.lastname: Restivo
authors.affiliation: Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy. Aldo.marrone@unina2.it.
authors.forename: Aldo
authors.initials: A
authors.lastname: Marrone
authors.affiliation: Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy. mauro.giordano@unina2.it.
authors.forename: Mauro
authors.initials: M
authors.lastname: Giordano
authors.affiliation: Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples 80100, Italy. rosa.zampino@unina2.it.
authors.forename: Rosa
authors.initials: R
authors.lastname: Zampino
mesh_terms: D015897:Comorbidity; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications / Q000821:virology*; D006801:Humans; D050356:Lipid Metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000453:epidemiology* / Q000821:virology; D015995:Prevalence
chemical_list: D005947:Glucose
keywords: HCC; HCV-associated NAFLD; atherosclerosis; diabetes; insulin resistance; liver fibrosis; metabolic syndrome