The risk factors for hepatocellular carcinoma (HCC) in immune inactive chronic hepatitis B (CHB) have not been clarified. The aim of this study was to investigate the predictive factors for HCC inimmune inactive CHB.

A total of 337 patients in immune inactive CHB were consecutively enrolled in Kangdong Sacred Heart Hospital from 1995 to 2017. Univariate and multivariate analyses were performed to identify the independent risk factors for HCC development.

During the mean 63 months of follow-up, the incidence of HCC of study population was 4.5% (15/337). Patients who developed HCC were older, had more cirrhosis at baseline, and were more likely to experience ALT elevation>2 X upper limit of normal (ULN) during follow-up than those without HCC. In Cox regression analysis, increased ALT levels>2 X ULN during follow-up (hazard ratio [HR], 3.774; 95% confidence interval [CI], 1.145–12.443; P=0.029] and presence of cirrhosis (HR, 11.768; 95% CI, 3.350–41.336; P<0.001) were identified as the independent factors for HCC in immune inactive CHB. With increasing number of risk factors, the respective cumulative incidence of HCC at 10 years was 6.3%, 8.8%, and 63.5%.

Underlying cirrhosis and hepatic inflammation reflected by increased ALT levels>2 X ULN were significant predictors for HCC in immune inactive CHB. ALT elevation showed a synergistic effect in HCC development combined with cirrhosis. It suggests that patients with high serum ALT levels, especially those with cirrhosis, are required closer surveillance for HCC even in immune inactive CHB.