Risk of hepatocellular carcinoma development in long-term nucles(t)ide analog suppressed patients with chronic hepatitis B

Aim: In long-term nucleos(t)ide analog (NA) suppressed patients with chronic hepatitis B (CHB), hepatocellular carcinoma (HCC) can still develop. Few data exist on the incidence and the predictors of HCC development beyond the first five years in long-term treated patients. To assess the prevalence, incidence, and risk factors for HCC development in a real-life cohort of successfully NA-treated CHB patients for more than five years. Methods: All CHB patients under NAs for ≥ 60 months with stable virologic response were enrolled. HCC surveillance was carried out using liver ultrasound and dosing of serum alpha-fetoprotein every year in patients with CHB and every six months in cirrhotic patients. The baseline PAGE-B score was calculated for each patient. Results: 343 patients (76% male, 86% HBeAg-negative, 30% cirrhotic) were enrolled. During a median (IQR) follow-up of 144 (105-182) months, 21 patients (6%) developed HCC despite virologic suppression (incidence rate 40 cases/1000 person-years follow-up). In multivariate analysis, higher PAGE B score [adjusted Hazard Ratio, aHR 1.26 (95%CI: 1.13-1.54), P = .022] and cirrhosis [aHR 9.71 (95%CI: 2.02-46.48), P = .005] were predictors of HCC development. PAGE B score showed a significant association with HCC (R2 0.225, P < .001) and good prognostic capacity (AUC 0.863) of HCC. Conclusions: Our results confirm that in successfully NA-treated CHB patients, sustained viral replication suppression does not abolish the risk of HCC. The PAGE-B score could be a useful tool for identifying high-risk subjects.