Metabolic Manifestations and Complications Associated With Chronic Hepatitis C Virus Infection

Abstract

Chronic hepatitis C virus (HCV) infection is associated with many extrahepatic manifestations that contribute to morbidity and mortality. It is especially important to be aware of metabolic manifestations and serious complications that affect other organs and cancer risks. Chronic HCV infection itself contributes to de novo development of insulin resistance and hepatic steatosis, both of which increase the risk of cardiovascular diseases. Through these metabolic pathways (as well as through other hypothesized mechanisms that involve lipid metabolism, systemic inflammatory signals, and endothelial dysfunction), chronic HCV infection also contributes to significant systemic cardiovascular morbidity and mortality. While chronic HCV infection contributes to incident development of metabolic complications, the presence of concurrent metabolic diseases also contributes to disease progression, such as higher risks of hepatocellular carcinoma and progression to advanced fibrosis, among patients with chronic HCV infection. The implications of these observations are particularly important given the rising prevalence of obesity and metabolic syndrome in the United States and worldwide. Furthermore, concurrent nonalcoholic fatty liver disease, either as a result of underlying metabolic syndrome or as a direct result of HCV-induced fatty liver disease, further complicates the management of chronic HCV-infected patients. Greater awareness is needed toward the systemic manifestations of chronic HCV infection, with focused attention on the associated metabolic manifestations and complications. Successful treatment and cure of chronic HCV infection with the currently available, highly effective antiviral therapies will significantly improve long-term outcomes among these patients. It is also important to recognize and address the associated metabolic manifestations and complications to reduce cardiovascular-related morbidity and mortality.

Keywords: Insulin resistance; cardiovascular diseases; chronic hepatitis C virus infection; diabetes mellitus; fatty liver; metabolic syndrome.

Figure

Trends in the etiology of liver disease leading to liver transplantation waitlist registration (A). Trends in the etiology of liver disease leading to HCC requiring liver transplantation (B) and the total number of HCC patients transplanted (C). ALD, alcoholic liver disease; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; modified NASH, nonalcoholic steatohepatitis plus a cryptogenic or unknown etiology with a body mass index of at least 30; NASH, nonalcoholic steatohepatitis.

Figure

Trends in the etiology of liver disease leading to liver transplantation waitlist registration (A). Trends in the etiology of liver disease leading to HCC requiring liver transplantation (B) and the total number of HCC patients transplanted (C). ALD, alcoholic liver disease; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; modified NASH, nonalcoholic steatohepatitis plus a cryptogenic or unknown etiology with a body mass index of at least 30; NASH, nonalcoholic steatohepatitis.