Incidence and Risk Factors of Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Treated with Direct-Acting Antivirals

Background: Conflicting data regarding the incidence of hepatocellular carcinoma (HCC) after cure of HCV infection with direct-acting antivirals (DAAs) remains. We investigated the incidence and risk factors to HCC after treatment with DAAs followed up for five years. Methods: A total of 1075 HCV patients ≥ 18 years were treated with DAAs from 2015 to 2019 and followed until 2022. Ultrasonography was performed before DAAs and each 6 months thereafter. Results: Of the total, 51/1075 (4.7%) developed HCC in the median of 40 (IQR 25–58) months: 26/51 (51%) male, median age 60 (IQR 54–66) years, alpha-fetoprotein (AFP) 12.2 (IQR 6.1–18.8) ng/mL, 47/51 (92.1%) cirrhotic 78.7%, 8/51 (15.7%) without sustained virological response (SVR). Seventeen percent had non-characterized nodules before DAAs. Cumulative HCC incidence was 5.9% in 5 years. Overall incidence was 1.46/100 patient-years (PY) (95% CI = 1.09–1.91), being 2.31/100 PY (95% CI = 1.70–3.06), 0.45/100 PY (95% CI = 0.09–1.32) and 0.20/100 PY (95% CI 0.01–1.01) in METAVIR F4, F3 and F2, respectively, and the main risks to HCC were non-characterized nodule, cirrhosis, high AFP values and non-SVR. Conclusion: HCV cure reduced risk for HCC, but it still occurred particularly in cirrhotic patients. Some risk factors can be identified to predict early HCC diagnosis.