Abstract
BACKGROUND: The impact of direct acting antivirals (DAAs) on hepatitis C virus related hepatocellular carcinoma (HCV-HCC) incidence after sustained virologic response (SVR) remains controversial. We aimed to compare long-term HCC incidence after SVR induced by interferon (IFN) and DAA therapy, also to construct a nomogram model for predicting long-term HCC incidence after HCV cure. METHODS: A total of 405 patients treated with IFN or DAA were analyzed. 200 patients who achieved SVR were assigned to IFN and DAA group by propensity score matching. The COX regression, LASSO logistic regression, and best subset regression (BSR) were adopted to select variables independently associated with HCC incidence and construct nomogram. RESULTS: After a median follow-up period of 72.0 (interquartile range 57.5–90.0) months, HCC developed in 7 (7%) and 15 (15%) patients in IFN and DAA groups, respectively. The cumulative HCC rates were comparable between the two groups (HR: 0.917, 95% CI: 0.262–1.968, P = 0.520). Out of all three models constructed by COX, LASSO and BSR, model 2 and 3 both contained gender, age, platelet count and alkaline phosphatase, exhibited the minimum Akaike Information Criterion (174.54) and the best predictive performance for 8-year HCC incidence (AUROC = 0.905). Using these four factors, a novel nomogram was established to predict 8-year HCC occurrence following HCV eradication. It showed significant clinical benefit according to decision curve analysis. CONCLUSIONS: DAAs exert the same long-term protect role against HCC as IFN treatment, though the development of HCC is still inevitable. Herein, we developed a 8-year HCC-predicting nomogram that can be used to guide clinical screening strategies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12876-025-04412-x.