Direct-acting antiviral agents do not increase the incidence of hepatocellular carcinoma development: a prospective, multicenter study

Background While achieving sustained virological response (SVR) following interferon-based or direct-acting antiviral agent (DAA) treatments reduces the incidence of hepatocellular carcinoma (HCC), an increase in unexpected early occurrence or recurrence of HCC after hepatitis C virus elimination by DAA treatments has been reported. We prospectively investigated the incidence and risk factors of HCC after DAA treatment in a large multicenter cohort in Japan. Methods Patients with chronic hepatitis C with or without cirrhosis who were treated with DAAs and obtained SVR were enrolled. DAAs were administered for 3 or 6 months. A total of 2552 patients were enrolled. Results Of these, 70 patients (2.7%) developed HCC. The 12-, 24-, and 36-month cumulative HCC incidences were 1.3%, 2.9%, and 4.9% in all patients; 2.5%, 5.2%, and 10.0% in those with cirrhosis; and 0.9%, 2.1%, and 2.9% in those without cirrhosis, respectively. Multivariate analysis revealed age, sex, gamma-glutamyl transpeptidase level, and fibrosis-4 index to be independent factors associated with HCC. Patients with these four factors had an approximately six-to-sevenfold increased risk for HCC development. Five patients with large and early tumor occurrence did not receive contrast imaging examinations before treatment. Conclusion Although the results of our prospective study suggested that achieving SVR by DAA treatment reduces the incidence of HCC, HCC development still occurs. Careful follow-up is important in patients with risk factors.