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World J Gastroenterol. Mar 21, 2014; 20(11): 2825-2838
Published online Mar 21, 2014. doi: 10.3748/wjg.v20.i11.2825
Hepatitis C virus and metabolic disorder interactions towards liver damage and atherosclerosis
Umberto Vespasiani-Gentilucci, Paolo Gallo, Antonio De Vincentis, Giovanni Galati, Antonio Picardi
Umberto Vespasiani-Gentilucci, Paolo Gallo, Antonio De Vincentis, Giovanni Galati, Antonio Picardi, Internal Medicine and Hepatology Unit, University Campus Bio-Medico of Rome, 00128 Rome, Italy
Author contributions: Vespasiani-Gentilucci U, Gallo P, De Vincentis A, Galati G and Picardi A contributed to this manuscript.
Correspondence to: Antonio Picardi, MD, PhD, Internal Medicine and Hepatology Unit, University Campus Bio-Medico of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy. a.picardi@unicampus.it
Telephone: +39-6-225411207 Fax: +39-6-225411944
Received: October 29, 2013
Revised: December 25, 2013
Accepted: January 3, 2014
Published online: March 21, 2014
Processing time: 140 Days and 11.4 Hours
Abstract

Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide, and alterations of glucose metabolism have reached pandemic proportions in western countries. However, the frequent coexistence between these two conditions is more than simply coincidental, since HCV can induce insulin resistance through several mechanisms. Indeed, the virus interferes with insulin signaling both directly and indirectly, inducing the production of pro-inflammatory cytokines. Furthermore, the entire viral life cycle has strict interconnections with lipid metabolism, and HCV is responsible for a “viral” steatosis which is frequently superimposed to a “metabolic” one. Several evidences suggest that HCV-induced metabolic disorders contribute both to the evolution of liver fibrosis and, likely, to the progression of the other disorders which are typically associated with altered metabolism, in particular atherosclerosis. In the present review, we will examine in depth the links between HCV infection and insulin resistance, liver steatosis and diabetes, and analyze the impact of these interactions on the progression of liver fibrosis and atherosclerosis. Special attention will be focused on the highly debated topic of the relationship between HCV infection and cardiovascular disease. The available clinical literature on this item will be broadly reviewed and all the mechanisms possibly implied will be discussed.

Keywords: Hepatitis C virus; Metabolism; Insulin resistance; Diabetes mellitus; Steatosis; Fibrosis; Atherosclerosis; Cardiovascular risk

Core tip: In this review we will analyze the mechanisms possibly contributing to the relationship between hepatitis C virus (HCV) infection and altered metabolism, as well as the clinical data suggesting that HCV-induced metabolic disorders favour both the progression of liver damage in terms of steatosis/fibrosis and the development of atherosclerosis. Particular attention will be devoted to the highly debated topic concerning the link between HCV infection and cardiovascular disease, a time-related interpretation on the factors impacting cardiovascular risk in the course of HCV infection will be provided, and, finally, the complex virus/host interplay will be graphically synthesized to provide an intuitive picture of the item.