No difference between direct-acting antivirals for hepatitis C in hepatocellular carcinoma risk.

BACKGROUND AND AIMS: It is unclear whether there are differences between direct-acting antivirals (DAAs) for hepatitis C virus in risk of hepatocellular carcinoma (HCC) after antiviral therapy. We aimed to compare different DAA regimens with respect to risk of de novo HCC following antiviral therapy. PATIENTS AND METHODS: We identified 33 137 patients who initiated hepatitis C virus antiviral treatment in the Veterans Affair healthcare system between 6 December 2013 and 31 December 2015 with one of four DAA-only regimens (± ribavirin): paritaprevir/ritonavir/ombitasvir/dasabuvir (n=6289), sofosbuvir (n=4356), sofosbuvir+simeprevir (n=3210), and ledipasvir/sofosbuvir (n=19 282). We retrospectively followed patients until 15 June 2017 to identify incident (de novo) cases of HCC. We used propensity score-adjusted Cox proportional hazards regression to compare different DAA regimens with respect to HCC risk.
RESULTS: During a mean follow-up of 1.52 years, 741 new cases of HCC were diagnosed after antiviral treatment (annual incidence=1.47%). Patients treated with sofosbuvir+simeprevir had the highest annual HCC incidence (2.47%), followed by sofosbuvir (1.91%), ledipasvir/sofosbuvir (1.26%), and paritaprevir/ritonavir/ombitasvir/dasabuvir (0.95%). However, there were great differences between DAA-treated patients in the prevalence of cirrhosis, markers of advanced fibrosis, thrombocytopenia, and other HCC risk factors. After adjustment for baseline characteristics associated with HCC, there were no significant differences in HCC risk between the four DAA regimens.
CONCLUSION: There are no significant differences between DAA regimens in HCC risk after antiviral treatment. This suggests that DAAs do not have direct carcinogenic effects as it would be unlikely that different DAAs would have identical carcinogenic effects.