Abstract
Current antiviral therapies cannot achieve eradication of hepatitis B virus (HBV) and can reduce but not eliminate the risk of hepatocellular carcinoma (HCC) in patients with chronic HBV infection. The present study aimed to identify the risk factors for HCC development by analyzing nucleoside analogue (NA)-treated patients as a retrospective cohort using fibrosis-4 index (FIB-4 index) as a non-invasive fibrosis marker. A total of 260 patients with HBV receiving NAs without a history of HCC between January 2001 and January 2021 were included in the present study. The incidence of HCC in patients with HBV during NA therapy and the factors contributing to HCC occurrence were identified using clinical characteristics and blood test results. Among the 260 patients, 40 patients (15.4%) developed HCC. Univariate and multivariate analysis showed that age [hazard ratio (HR), 1.03; P=0.045], male sex (HR, 3.14; P<0.01) and FIB-4 index at 6 months after NA treatment <1.95 (HR, 4.35; P<0.01) correlated with the incidence of HCC. The cumulative incidence of HCC in patients with FIB-4 index at 6 months after NA treatment >1.95 was significantly higher compared with that in patients with FIB-4 index ≤1.95 (P<0.01). Multivariate analysis in patients in which serum α-fetoprotein (AFP) level at 6 months after NA treatment was measured showed that FIB-4 index >1.95 (HR, 8.27; P=0.014) and serum AFP level >4 ng/ml (HR, 4.26; P=0.033) contributed to HCC occurrence. FIB-4 index at 6 months after NA treatment and serum AFP levels at 6 months after NA treatment were predictors for the development of HCC in patients with HBV during NA treatment. Further study of hepatocarcinogenesis during NA with a longer follow-up period and larger numbers of participants is required.