Impact of Interferon-Free Direct-Acting Antivirals on the Incidence of Extrahepatic Malignancies in Patients with Chronic Hepatitis C

Background: The incidence of extrahepatic malignancies (EHMs) after hepatitis C virus (HCV) eradication by interferon (IFN)-based and IFN-free direct-acting antivirals (DAAs) treatment remains unclear.

Aims: The aim was to evaluate the cumulative incidence of EHMs diagnosed for the first time after the antiviral treatments.

Methods: We analyzed a total 527 patients with chronic HCV infection and without prior history of any malignancies who achieved sustained virological response by antiviral treatments, including IFN-based (n = 242) or IFN-free DAAs (n = 285). The baseline predictors for EHM occurrence were analyzed using Cox regression analysis.

Results: Thirty-two patients were diagnosed with EHMs, 14 in IFN-based and 18 in IFN-free DAAs, respectively. The total duration of follow-up was 1,796 person-years in IFN-based and 823 person-years in IFN-free DAAs. The incidence of EHMs in IFN-based and IFN-free DAAs was 7.8 and 21.9 per 1,000 person-years, respectively. The cumulative incidence of EHMs was significantly higher in IFN-free DAAs than IFN-based (p = 0.002). IFN-free DAAs was a single independent predictor for incidence of EHMs (p = 0.012). As for gender, the incidence of EHMs was significantly higher in IFN-free DAAs only in the female cohort (p = 0.002). After propensity score matching, IFN-free DAAs was a single independent predictor for incidence of EHMs in the female patients (p = 0.045).

Conclusions: The incidence of EHMs after HCV eradication is higher in IFN-free DAAs than IFN-based regimens, especially in female patients. We should carefully follow-up not only HCC but also EHMs after IFN-free DAAs regimens.