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World J Gastroenterol. Jun 21, 2014; 20(23): 7089-7103
Published online Jun 21, 2014. doi: 10.3748/wjg.v20.i23.7089
Pathogenesis and significance of hepatitis C virus steatosis: An update on survival strategy of a successful pathogen
Amedeo Lonardo, Luigi Elio Adinolfi, Luciano Restivo, Stefano Ballestri, Dante Romagnoli, Enrica Baldelli, Fabio Nascimbeni, Paola Loria
Amedeo Lonardo, Stefano Ballestri, Dante Romagnoli, Enrica Baldelli, Fabio Nascimbeni, Paola Loria, Division of Internal Medicine, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41126 Modena, Italy
Luigi Elio Adinolfi, Luciano Restivo, Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, 80100 Naples, Italy
Author contributions: Lonardo A and Adinolfi LE contributed equally to this paper by conceiving the idea of this review and writing the first draft of the manuscript; all the authors critically revised, edited and approved the submission.
Correspondence to: Amedeo Lonardo, MD, Division of Internal Medicine, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Giardini 1355, 41126 Modena, Italy. a.lonardo@libero.it
Telephone: +39-59-3961807 Fax: +39-59-3961322
Received: September 27, 2013
Revised: January 17, 2014
Accepted: April 1, 2014
Published online: June 21, 2014
Processing time: 267 Days and 1.2 Hours
Abstract

Hepatitis C virus (HCV) is a successful pathogen on the grounds that it exploits its host’s metabolism to build up viral particles; moreover it favours its own survival by inducing chronic disease and the development of specific anatomic changes in the infected organ. Steatosis, therefore, is associated with HCV infection by necessity rather than by chance alone. Approximately 6% of HCV patients have steatohepatitis. Interestingly, HCV steatosis occurs in the setting of multiple metabolic abnormalities (hyperuricemia, reversible hypocholesterolemia, insulin resistance, arterial hypertension and expansion of visceral adipose tissue) collectively referred to as “hepatitis C-associated dysmetabolic syndrome” (HCADS). General, nonalcoholic fatty liver disease (NAFLD)-like, mechanisms of steatogenesis (including increased availability of lipogenic substrates and de novo lipogenesis; decreased oxidation of fatty substrates and export of fatty substrates) are shared by all HCV genotypes. However, genotype 3 seemingly amplifies such steatogenic molecular mechanisms reported to occur in NAFLD via more profound changes in microsomal triglyceride transfer protein; peroxisome proliferator-activated receptor alpha; sterol regulatory element-binding proteins and phosphatase and tensin homologue. HCV steatosis has a remarkable clinical impact in as much as it is an acknowledged risk factor for accelerated fibrogenesis; for impaired treatment response to interferon and ribavirin; and development of hepatocellular carcinoma. Recent data, moreover, suggest that HCV-steatosis contributes to premature atherogenesis via both direct and indirect mechanisms. In conclusion, HCV steatosis fulfills all expected requirements necessary to perpetuate the HCV life cycle. A better understanding of the physiology of HCADS will likely result in a more successful handling of disease with improved antiviral success rates.

Keywords: Atherosclerosis; Fibrosis; Hepatitis C-associated dysmetabolic syndrome; Hepatocellular carcinoma; Steatohepatitis; Sustained virological response; Hepatitis C virus

Core tip: Hepatitis C virus (HCV) steatosis occurs in the setting of multiple abnormalities collectively referred to as “hepatitis C-associated dysmetabolic syndrome”. General, nonalcoholic fatty liver disease-like, mechanisms of steatogenesis are shared by all HCV genotypes. However, genotype 3 seemingly amplifies such steatogenic molecular mechanisms. HCV steatosis has a remarkable clinical impact in accelerating fibrogenesis; impairing treatment response to interferons and ribavirin; and favouring the development of hepatocellular carcinoma and atherosclerosis. In conclusion, steatosis fulfills all expected requirements necessary to perpetuate the HCV life cycle and is associated with HCV infection by necessity rather than by chance.