Hepatitis C virus-associated and metabolic steatosis. Different or overlapping diseases?

Hepatic steatosis is the hallmark of nonalcoholic fatty liver disease (NAFLD), which is the consequence of multiple metabolic derangements among which insulin resistance plays a pivotal role. Steatosis is, also, a feature of hepatitis C virus (HCV) infection. However, in chronic hepatitis C, the prevalence of steatosis is 2.5-fold more elevated than that expected by a chance concurrence with NAFLD, suggesting that HCV may be implied in the development of steatosis. As observed in NAFLD, in patients infected with HCV genotype 1 steatosis is associated with an increased body mass index. On the other hand, in patients infected with genotype 3 the extent of steatosis strictly correlates with the viral load indicating that steatosis is mainly "virus-related". Regardless of the "metabolic" or "viral" etiology, hepatic steatosis in HCV contributes to the progression of liver fibrosis, to the development of hepatocellular carcinoma and to an impaired response to interferon treatment. Features such as obesity, insulin resistance and type 2 diabetes mellitus are shared by NAFLD and HCV-associated steatosis. In addition, HCV infection, directly or through steatosis, favors the development of type 2 diabetes mellitus. Hyperlipidemia is an independent predictor of the development of NAFLD, but not of HCV-associated steatosis. Arterial hypertension is common in nonalcoholic steatohepatitis patients, and HCV infection has recently been acknowledged as an independent risk factor for atherosclerosis. The role of iron in the progression of both NAFLD and HCV-associated steatosis remains controversial while lipoperoxidation and oxidative stress are pathogenic mechanisms shared by both. Some metabolic risk factors may be shared by both HCV-associated steatosis and NAFLD although the disease progression and pathophysiological background may be different. Preliminary data suggest that the therapeutic options for NAFLD may also be useful to improve HCV-associated steatosis.