Hepatocellular Carcinoma Risk Steadily Persists over Time Despite Long-Term Antiviral Therapy for Hepatitis B: A Multicenter Study

Long-term antiviral therapy (AVT) for chronic hepatitis B (CHB) reduces the risk of hepatocellular carcinoma (HCC). We assessed the temporal trends in the incidence of HCC over time during long-term AVT among Asian patients with CHB.Patients with CHB receiving entecavir/tenofovir (ETV/TDF) as a first-line antiviral were recruited from four academic hospitals in the Republic of Korea. We compared the incidence of HCC during and after the first 5 years of ETV/TDF treatment.Among 3,156 patients, the median age was 49.6 years and males predominated (62.4%). During the follow-up, 9.0% developed HCC. The annual incidence of HCC per 100 person-years during the first 5 years (n = 1,671) and after the first 5 years (n = 1,485) was statistically similar (1.93% vs. 2.27%, P = 0.347). When the study population was stratified according to HCC prediction model, that is, modified PAGE-B score, the annual incidence of HCC was 0.11% versus 0.39% in the low-risk group (<8 points), 1.26% versus 1.82% in the intermediate-risk group (9-12 points), and 4.63% versus 5.24% in the high-risk group (≥13 points; all P > 0.05). A Poisson regression analysis indicated that the duration of AVT did not significantly affect the overall trend of the incidence of HCC (adjusted annual incidence rate ratio = 0.85; 95% confidence interval, 0.66-1.11; P = 0.232).Despite long-term AVT, the risk of HCC steadily persists over time among patients with CHB in the Republic of Korea, in whom HBV genotype C2 predominates.Careful HCC surveillance is still essential.