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

Abstract

Summary 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.

Letter: fatty liver disease could have been a confounding factor for phase change in patients with chronic hepatitis B in the immune‐tolerant phase—authors' reply

“…We appreciate the letter from Wan et al, 1 which voiced several concerns about our study 2 . We demonstrated that an HBV‐DNA level >10 7 IU/mL independently predicted a decreased risk of phase change.…”

Letter: fatty liver disease could have been a confounding factor for phase change in patients with chronic hepatitis B in the immune tolerant phase

“…It would be more convincing if the 95% confidence interval of these variables in univariate analysis were also presented. Second, we observed in Table 2 of the original paper, 1 that the subjects with phase change were more likely to have fatty liver (23.6%) compared to patients with persistent immune tolerant phase (15.6%, P = 0.002). The body mass index was also higher in the phase‐change group.…”

“…The impressive study from Lee et al 1 is of particular interest. In this population‐based cohort study, the investigators explored the phase‐change rate and the hepatocellular carcinoma incidence in 946 patients with chronic hepatitis B in the immune tolerant phase.…”

Editorial: risk assessment for chronic hepatitis B patients in the immune tolerant phase—both definition and selection matter

“…In the multicentre cohort study by Lee et al, 6 the cumulative incidence of hepatocellular carcinoma (HCC) at 10 years of follow‐up was 1.7% among 946 Korean patients (mean age, 36.8 years) who presented with the IT‐phase characteristics. Meanwhile, it was estimated that 70.7% of the study population would leave the IT phase over 10 years and most of them (n = 378 of 470) changed to HBeAg‐negative chronic hepatitis.…”