Baseline and post-treatment fibrosis-4 scores to predict hepatocellular carcinoma after direct-acting antiviral therapy

INTRODUCTION: Patients with chronic hepatitis C remain at risk of hepatocellular carcinoma (HCC) even after attaining sustained virological response at 12 weeks (SVR12). The optimal strategy to stratify HCC risk, particularly in non-cirrhotic patients, remains unclear. This study compared the predictive performance of baseline and post-SVR12 fibrosis-4 index (FIB-4 index) for incident HCC. METHODS: We conducted a post hoc analysis of consecutive patients with chronic hepatitis C treated with direct-acting antivirals between 2018 and 2019, with follow-up for de novo HCC occurrence. Primary predictors were FIB-4 at baseline, post-SVR12 and their dynamic change. The primary outcome was the development of post-SVR12 HCC. RESULTS: Among 762 patients, 2.4% developed HCC over a median follow-up of 53 months. Patients who developed HCC were older (58 years vs. 52 years; P = 0.003), exclusively male, and had a higher baseline FIB-4. The FIB-4 values declined after SVR12 (2.9 ± 3.6 vs. 2.1 ± 2.6, P = 0.043), resulting in a different optimal threshold for HCC prediction (baseline 2.9; post-SVR 2.4). Both baseline and post-SVR12 FIB-4 showed strong and comparable predictive performance (area under the receiver operating characteristic curves 0.91 vs. 0.88, P = 0.279). By contrast, changes in FIB-4 were not predictive of HCC risk. CONCLUSION: Both baseline and post-SVR12 FIB-4 reliably predict HCC after direct-acting antiviral-induced SVR, although the optimal threshold differs due to post-SVR improvements. A post-SVR12 FIB-4 of less than 1.3 identifies a very low-risk group who may be safely discharged from long-term HCC surveillance.