HEPATITIS B SURFACE ANTIGEN LEVELS DURING NATURAL HISTORY OF CHRONIC HEPATITIS B

초록

Background: Chronic hepatitis B (CHB) represent four unique phases during natural history although these phases do not occur in all patients nor occur sequencially. Recently, sensitive and reliable method for quantifying HBsAg level has been emerged. Several reports suggested that HBsAg level could be one of valuable markers for clinical course of CHB. However, there has been a few reports for HBsAg levels and these included only small CHB patients with genotype C. Exclusively, almost all hepatitis B virus has been known to be genotype C in Korea. So, we investigated HBsAg level in each four phase and the relationship between HBsAg level and ALT or HBV DNA in Korea. Methods: We retrospectively reviewed the medical records of 2,594 HBsAg positive patients who received HBsAg titeration test (Archtect HBsAg QT assay, Abott) from Sep 2009.to April 2011. Among them, the patients with history of antiviral therapy, hepatocellular carcinoma, and coexisted chronic liver disease have been excluded. Immune tolerance (IT) was defined as HBeAg(+), ALT < ULN, HBV > 107 IU/ml, immuneclearance (IC) was defined as HBeAg(+), ALT > 2ULN, HBV > 20,000 IU/ml, HBeAg negative hepatitis (ENH) was defined as HBeAg(-), ALT > 2ULN, HBV > 2,000 IU/ml, low replicative phase was defined as maintaining HBeAg(-), ALT < 2ULN, HBV < 2,000 IU/ml more than 6 months. Result: Total 391 eligible patients has been classified into four phases, IT, IC, LR and ENH was 93, 110, 66 and 122, respectively. The mean age off our phase was 37, 38, 49 and 46 years (p<0.001, ANOVA), mean ALT was 28, 365, 24 and 332 IU/L (p<0.001, ANOVA)and mean HBV DNA was 8.1, 7.5, 2.2 and 6.0 log10 IU/ml(p<0.001, ANOVA). The mean HBsAg level of four phase was 4.36 ±0.67, 3.78 ±0.68, 2.60 ±1.13 and 3.35 ±0.51.(p<0.001, ANOVA) Using HBsAg level, the AUROC to differenciate between LR and ENH was 0.713 (p<0.001), IC and IT was 0.779 (p<0.001). In whole patients, HBsAg level was well correlated with HBV DNA (p<0.001, r=0.665). In IT, IC and LR patients, HBsAg level was well correlated with HBV DNA(p<0.001, r=0.663; p<0.001, r=0.584; p<0.001, r=0.377, respectively) but HBsAg level did not correlated with HBV DNA in ENH patients (p=0.127, r=0.308) HBsAg level did not correlated with ALT. The mean HBsAg / HBV DNA level was 0.54±0.74, 0.52 ±0.09, 1.23 ±0.70, 0.60 ±0.17.(p<0.001, ANOVA) Conclusion: HBsAg level was significantly different across four phases of CHB natural history and significantly correlated with HBV DNA level in genotype C CHB. HBsAg level could be applied as a factor to differentiate CHB natural history.