Supplementary Material for: Recurrence of Hepatocellular Carcinoma in Hepatitis C Virus (HCV) Liver Transplant Recipients Treated with Pretransplant Direct-Acting Antiviral (DAA) Therapy

Background: Direct-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV). The impact of DAAs on recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains uncertain. Objective: We aimed to evaluate the risk of HCC recurrence in LT recipients cleared of HCV with DAAs at the time of LT compared to a control group of LT recipients who were viremic at the time of LT. Methods: The study was a single-center, retrospective cohort study of patients undergoing LT for HCV-related HCC from 2002 to 2017. We compared time to post-LT HCC recurrence in patients with a sustained virological response (SVR) from DAAs prior to LT (DAA group) to patients who were viremic at LT (HCV+ group) using Kaplan-Meier analysis. We performed a secondary analysis comparing post-LT HCC recurrence in the DAA group to LT recipients with SVR from interferon-based treatment prior to LT (IFN group). Results: One hundred fifty-one patients underwent LT for HCC related to HCV: 34 patients in DAA group, 95 patients in HCV+ group, and 22 in IFN group. Kaplan-Meier estimates of being HCC free were 96.2, 96.2, and 78.8% at 6, 12, and 24 months in DAA group, respectively, and 100, 98.6, and 95.8% at 6, 12, and 24 months in the HCV+ group, respectively; p = 0.08. There was no difference observed for HCC recurrence between the DAA and IFN groups. In a multivariate Cox proportional hazards model, DAA use increased the risk of post-LT HCC recurrence (HR 5.2, 95% CI 0.9–29.81, p = 0.07). Conclusions: A strong trend was observed on both Kaplan-Meier and multivariate analyses toward increased post-LT HCC recurrence in patients who achieved SVR prior to LT with DAAs compared to patients who were viremic at LT. Caution is required when considering pre-LT treatment of HCV with DAAs in patients with HCC.