Nonzero Risk of Hepatocellular Carcinoma Even after Sustained Virological Response

Abstract

Approximately 130 to 150 million people are chronically infected with hepatitis C virus (HCV) in the world. HCV infection is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). The existence of hepatitis C— originally identifiable only as a type of non-A, non-B hepatitis— was suggested in the 1970s and proven in 1989. In the treatment of chronic hepatitis C (CHC), antiviral therapy has seen brilliant advances and rapid evolution in efficacy as well as safety and tolerability within recent several years. New antiviral agents now promise excellent sustained virological response (SVR) rates. 1 After the widespread prescription of direct-acting antivirals (DAAs), the incidence of HCC will decrease gradually in the upcoming decades. However, the risk of HCC still remains in patients with advanced fibrosis, even though SVR reduces the progression to HCC. 2 Therefore, current guidelines recommended continued HCC surveillance for patients with liver cirrhosis even after SVR. 3 In a recent meta-analysis of observational studies, SVR is associated with a reduction in the relative risk for HCC for persons at all stages of liver disease (hazard ratio, 0.24; p<0.01). 4 This meta-analysis suggests that interferon (IFN) therapy is beneficial in reduction of HCC development after SVR. However, even if the absolute reduction in risk was 4.6%, approximately 1.5% of the patients with SVR developed HCC. Up to now, there is no data supporting long-term benefits of SVR achieved with DAAs-based regimens in the risk of HCC development because of insufficient follow-up time. In the near future, DAA-based regimens will induce the high SVR rates and increase the numbers of patients with SVR. Consequently, a nonzero risk of HCC development after SVR may be the hot topic in many studies. 5 Furthermore, it is very important to identify patients at high risk for developing HCC. Several markers have been identified to predict the risk of HCC in CHC patients with SVR. For example, the pretreatment platelet count, alkaline phosphatase, and older age were significantly associated with the risk of HCC development. 6