Hepatocellular carcinoma in the post-hepatitis C virus era: Should we change the paradigm?

Abstract

Hepatocellular carcinoma (HCC) is a common and deadly malignancy. The disease usually develops on a background of chronic liver disease. Until recently, the most common etiology was infection with the hepatitis C virus (HCV). The advent of direct-acting antiviral (DAA) therapies has been a major breakthrough in HCV treatment. Sustained virologic response can now be achieved in almost all treated patients, even in patients with a high risk for the development of HCC, such as the elderly or those with significant fibrosis. Early reports raised concerns of a high risk for HCC occurrence after DAA therapy both in patients with previous resection of tumors and those without previous tumors. As the World Health Organization's goals for eradication of HCV are being endorsed worldwide, the elimination of HCV seems feasible. Simultaneous to the decrease in the burden of cirrhosis from HCV, non-alcoholic fatty liver disease (NAFLD) incidence has been increasing dramatically including significant increased incidence of cirrhosis and HCC in these patients. Surprisingly, a substantial proportion of patients with NAFLD were shown to develop HCC even in the absence of cirrhosis. Furthermore, HCC treatment and potential complications are known to be influenced by liver steatosis. These changes in etiology and epidemiology of HCC suggest the beginning of a new era: The post-HCV era. Changes may eventually undermine current practices of early detection, surveillance and management of HCC. We focused on the risk of HCC occurrence and recurrence in the post-HCV era, the surveillance needed after DAA therapy and current studies in HCC patients with NAFLD.

Keywords: Direct-acting antivirals; Hepatitis C virus; Hepatocellular carcinoma; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis.

Figure 1

Risk factors and their association with hepatocellular carcinoma in patients with chronic hepatitis C virus infection. SVR: Sustained virologic response.

Figure 2

Our suggested algorithm for hepatitis C virus patients after antiviral therapy. A: Suggested algorithm for hepatitis C virus patients [without previous hepatocellular carcinoma (HCC)] after treatment with direct-acting antiviral according to their risk to develop HCC and recommended surveillance strategy; B: Our surveillance strategy for HCC recurrence after DAA therapy. SVR: Sustained virologic response; AFP: Alpha-fetoprotein; CT: Computed tomography; MRI: Magnetic resonance imaging; HCC: Hepatocellular carcinoma.