Hepatocellular carcinoma risk following direct-acting antiviral HCV therapy: A systematic review, meta-analyses, and meta-regression

Background & Aims: The risk of hepatocellular carcinoma (HCC) occurrence or recurrence following direct-acting antiviral (DAA) hepatitis C virus (HCV) therapy remains unclear. The aims of this study were to compare the rate of HCC occurrence in patients with HCV-related cirrhosis, following DAA vs. interferon (IFN)-based cure, and to compare the rate of HCC recurrence in patients who received curative HCC treatment, following DAA vs. IFN-based cure. Methods: A search was conducted for reports published between January 2000 and February 2017. Studies were included if they assessed HCC outcomes by type and response to HCV therapy. Random-effects meta-analyses were undertaken to determine a combined estimate of HCC incidence rate per 100/person-years (py) among patients with a sustained virological response (SVR). Results: A total of 41 studies (n = 13,875 patients), including 26 on HCC occurrence (IFN = 17, DAA = 9; prospective = 19, retrospective = 5, retrospective-prospective = 2), and 17 on HCC recurrence (IFN = 7, DAA = 10; prospective = 11, retrospective = 5 and retrospective-prospective = 1) were included. In studies assessing HCC occurrence, average follow-up was shorter (1.0 vs. 5.5 years), and average age older (60 vs. 52 years) in DAA studies. In studies assessing HCC recurrence, average follow-up was shorter (1.3 vs. 5.0 years), but average age similar (64 vs. 66 years) in DAA studies. HCC occurrence was 1.14/100 py (95% CI 0.86-1.52) and 2.96/100 py (95% CI 1.76-4.96) in IFN and DAA studies respectively. HCC recurrence was 9.21/100 py (95% CI 7.18-11.81) and 12.16/100 py (95% CI 5.00-29.58) in IFN and DAA studies respectively. In meta-regression adjusting for study follow-up and age, DAA therapy was not associated with higher HCC occurrence (RR 0.68; 95% CI 0.18-2.55; p = 0.55) or recurrence (RR 0.62, 95% CI 0.11-3.45, p = 0.56). Conclusion: There is no evidence for differential HCC occurrence or recurrence risk following SVR from DAA and IFN-based therapy. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.