Dr Grandhe is a resident in the Department of Medicine at Scripps Green Hospital in La Jolla, California. Dr Frenette is the medical director of liver transplantation and director of the hepatocellular carcinoma program at the Scripps Center for Organ Transplant at Scripps Green Hospital.
Chronic hepatitis C virus (HCV) infection has generally been associated with a slightly increased risk of developing hepatocellular carcinoma (HCC). For the past several decades, most patients with chronic HCV cirrhosis have been treated with pegylated interferon and ribavirin therapies, which were known to achieve sustained virologic response (SVR) but also carried their own side effects and toxicities. The recent implementation of direct-acting antiviral (DAA) treatments revealed an increased efficacy in difficult-to-treat populations and higher adherence rates given the all-oral nature of the regimens. However, while these regimens are excellent in terms of improving the side-effect profile and achieving SVR at a higher rate and in a shorter time frame than interferon and ribavirin, some researchers are now discovering an increased rate of de novo and recurrent HCC in patients with HCV cirrhosis compared to interferon treatment protocols. Although other studies were not able to reproduce similar findings, the question as to the role of DAA therapy in HCC occurrence after achieving SVR in patients with HCV cirrhosis continues to persist. Possible theories as to the mechanisms behind tumor relapse after DAA therapy include alterations of immunosurveillance and gene expression, a protective and antineoplastic effect from inflammation secondary to chronic HCV infection that is then abolished with DAA therapy, and delay in radiographic identification of previously undetectable tumors. This article reviews the current literature regarding concern for the possible increase of HCC after DAA therapy.