Extremely low risk of hepatocellular carcinoma development in patients with chronic hepatitis B in immune-tolerant phase

Background: Anti-viral therapy is not indicated for patients with chronic hepatitis B (CHB) in the immune-tolerant phase. Aims: To investigate the cumulative incidence of phase change and hepatocellular carcinoma (HCC) and independent predictors for phase change in patients with CHB in immune-tolerant phase. Methods: In total, 946 patients in immune-tolerant phase, defined as hepatitis B e antigen positivity, HBV-DNA >20 000 IU/mL and alanine aminotransferase (ALT) ≤40 IU/L, between 1989 and 2017 were enrolled from eight institutes. Results: The mean age of study population (429 men and 517 women) was 36.7 years. The mean ALT and HBV-DNA levels were 24.6 IU/L and 8.50 log₁₀ IU/mL, respectively. Of the study population, 476 (50.3%) patients remained in immune-tolerant phase throughout the study period (median: 63.6 months). The cumulative incidence rates of phase change and HCC at 10 years were 70.7% and 1.7%, respectively. Multivariate analyses revealed that HBV-DNA level >10⁷ IU/mL was associated independently with a reduced risk of phase change (hazard ratio [HR] = 0.734, P = 0.008), whereas a high ALT level, above the cut-off recommended in the Korean Association for the Study of the Liver guidelines (34 IU/L for men and 30 IU/L for women), was associated independently with a greater risk of phase change (HR = 1.885, P < 0.001). Conclusions: The criterion of HBV-DNA level > 10⁷ IU/mL may be useful to define immune-tolerant phase. In addition, an extremely low risk of HCC development was observed in patients with CHB in immune-tolerant phase.