Incidence and predictors of hepatocellular carcinoma beyond year 5 of entecavir therapy in chronic hepatitis B patients

Background Purpose The study compared the incidence and predictors of hepatocellular carcinoma (HCC) within and beyond year 5 of entecavir (ETV) therapy. Methods The study enrolled 1397 CHB patients who were naïve to nucleos(t)ide analogue (NA) treatment and had received ETV monotherapy for more than 12 months. Results The cumulative incidences of HCC at 3, 5, and 10 years of ETV treatment were 4%, 9.1%, and 15.8%, respectively. In the entire cohort, the annual incidence rates of HCC were 2.28% within the first 5 years and 1.34% within 5–10 years of therapy. The incidences of HCC did not differ significantly within and beyond 5 years of ETV therapy ( p = 0.53), including patients with cirrhosis ( p = 0.85) and without cirrhosis ( p = 0.47). At year 5 of treatment, the multivariate analysis showed that the fibrosis-4 (FIB-4) index and alpha-fetoprotein (AFP) levels were independent risk factors for HCC development beyond year 5. The 10-year cumulative incidences of HCC beyond year 5 in the high-risk group (FIB-4 > 2.20 and AFP > 3.21 ng/mL) and low-risk group (FIB-4 ≤ 2.20 and AFP ≤ 3.21 ng/mL) were 48.7% and 0%, respectively. APA-B score at 12 months and year 5 had a higher C-index for the prediction of HCC beyond year 5 than the PAGE-B at baseline and year 5 ( p = 0.003 and p = 0.039, respectively) Conclusions The HCC incidence tended to decrease but did not change significantly within and beyond 5 years of ETV therapy. The FIB-4 index and AFP levels at year 5 were predictive of HCC development beyond year 5 of ETV therapy.