Abstract
BACKGROUND: Treating chronic hepatitis C virus infection with direct-acting antivirals (DAAs) results in a sustained virological response (SVR) in most cases, but hepatocellular carcinoma (HCC) can occur in some patients after achieving SVR. Thus, this study comprehensively assessed the risk factors associated with the development of HCC during long-term follow-up in patients who achieved SVR. Furthermore, we aimed to identify a group of patients without prior HCC treatment who are at extremely low risk for HCC long after achieving SVR. METHODS: This retrospective cohort study included patients who achieved SVR after DAA therapy, and predictors contributing to the incidence of HCC were determined via Cox regression analysis. Specifically, we evaluated the factors contributing to the incidence of HCC among patients without previous HCC treatment later than 5 years after achieving SVR, and these were used to construct a predictive scoring system for HCC. RESULTS: Overall, 267 cases of HCC were observed during follow-up. Male sex, older age, previous HCC treatment before starting DAA therapy, excessive alcohol use, diabetes mellitus, elevated γ-GTP, low albumin, and low platelet count were independent predictors of HCC. Since previous HCC treatment strongly influenced the incidence of HCC after SVR, we further analyzed the risk factors for HCC among patients without previous HCC treatment. In that cohort, parameters at 5 years after achieving SVR that contributed to the incidence of HCC later than 5 years after SVR were an age of ≥ 70 years, diabetes mellitus (DM), and fibrosis-4 index(Fib-4) of ≥ 2.67. These three factors were used to create a scoring system, with scores of 0 to 3 predicting a 0.8%, 2.7%, 11.9%, and 28.8%, respectively, cumulative incidence rate of HCC later than 5 years after SVR. CONCLUSIONS: Using long-term follow-up data, we investigated the risk factors for HCC among patients who achieved SVR after DAA therapy. Previous HCC treatment strongly predicted HCC after SVR. Although this was a retrospective cohort study, among patients without previous HCC treatment, those younger than 70 years, without DM and with a Fib-4 index of < 2.67 had a very low risk of developing HCC later than 5 years after SVR. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12876-025-04451-4.