Abstract LB-150: Risk of de novo hepatocellular carcinoma development following use of direct acting antiviral medications for treatment of chronic hepatitis C virus infection
Authors: Antwi Samuel O. , Houten Holly K. Van , Sangaralingham Lindsey R. , Patel Tushar 
Published: August 2019

Abstract
Background: Direct acting antiviral medications (DAA) have become the mainstay for treatment of chronic hepatitis C virus (HCV) infection. However, some studies have suggested an increased risk of HCC development following use of DAAs for HCV compared with use of interferon-based medications (IFN), while other studies, mostly in Veterans Administration population in the United States, did not show an increase in HCC risk after the use of DAA in patients with HCV. To address these conflicting reports, we investigated the association between use of DAA for HCV and subsequent development of HCC in a large, longitudinal data with broad representation of individuals from various ages, ethnicities, and geographic regions across the United States.
Methods: A retrospective cohort study was performed using medical and pharmacy claims from the OptumLabs® Data Warehouse. The study included 9,532 incident HCV cases (2010-2016) of ages 18 years or older treated with DAA or IFN and did not have a prior diagnosis of HCC before initiation of the antiviral therapy. The participants were categorized into DAA-only or IFN-only groups. To account for confounding by indication, inverse probability of treatment weighting (IPTW) was performed to ensure balance in sociodemographic and treatment related factors between treatment groups. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for HCC risk, comparing DAA-only regimen with IFN-only regimen (reference).
Results: Median follow-up for the entire study cohort was 1.4 years, with a slightly longer follow-up for individuals in the IFN-only group (1.8 years) than for those in the DAA-only group (1.4 years). One hundred and seventy-one incident HCC cases developed during follow-up, with a higher occurrence of HCC in the DAA-only group (n=155; 11.9 cases per 1,000 person-years) than in the IFN-only group (n=16; 8.3 cases per 1,000 person-years). Compared with IFN-only treatment, use of DAA-only for HCV was not associated with an increase in HCC risk (HR=1.47, 95% CI: 0.89-2.42). Similarly, no association was found between use of DAA-only regimen and HCC risk among individuals with cirrhosis (HR=1.28, 95% CI: 0.71-2.31) or those without cirrhosis (HR =1.80, 95% CI: 0.64-5.03). When stratified by sustained virologic response (SVR), a measure of complete viral clearance, we noted a higher HCC risk associated with DAA-only regimen among individuals with SVR (HR=7.83, 95% CI: 1.54-39.88) and a lower risk for DAA-only regimen among those without SVR (HR=0.12, 95% CI: 0.02-0.95); however, the CIs are substantially wide, reflecting the small numbers in these subgroup analyses.
Conclusion: Despite some prior reports of increased risk of HCC development following use of DAA for HCV, this ethnically and geographically diverse study did not find compelling evidence indicating an increased HCC risk associated with use of DAA in patients with HCV when compared with use of IFN.
Citation Format: Samuel O. Antwi, Holly K. Van Houten, Lindsey R. Sangaralingham, Tushar Patel. Risk of de novo hepatocellular carcinoma development following use of direct acting antiviral medications for treatment of chronic hepatitis C virus infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-150.