Clinical features of HBsAg seroclearance in hepatitis B virus carriers in South Korea: A retrospective longitudinal study

Abstract

Aim: To investigate the characteristic features of hepatitis B surface antigen (HBsAg) seroclearance among Korean hepatitis B virus (HBV) carriers.

Methods: Carriers with HBsAg seroclearance were selected by analyzing longitudinal data collected from 2003 to 2015. The period of time from enrollment to the negative conversion of HBsAg (HBsAg-NC) was compared by stratifying various factors, including age, sex, hepatitis B e antigen (HBeAg), HBV DNA, sequential changes in the signal-to-cutoff ratio of HBsAg (HBsAg-SCR), as measured by qualitative HBsAg assay, and chronic liver disease on ultrasonography (US-CLD). Quantification of HBV DNA and HBsAg (HBsAg-QNT) in the serum was performed by commercial assay.

Results: Among the 1919 carriers, 90 (4.7%) exhibited HBsAg-NC at 6.2 ± 3.6 years after registration, with no differences observed among the different age groups. Among these carriers, the percentages of those with asymptomatic liver cirrhosis (LC) and hepatocellular carcinoma (HCC) at registration were 31% and 7.8%, respectively. The frequency of HBsAg-NC significantly differed according to the HBV DNA titer and US-CLD. HBeAg influenced HBsAg-NC in the 40-50 and 50-60 year age groups. HBsAg-SCR < 1000 was correlated with an HBsAg-QNT < 200 IU/mL. A gradual decrease in the HBsAg-SCR to < 1000 predicted HBsAg-NC. Six patients developed HCC after registration, including two before and four after HBsAg-NC. The rate at which the patients developed new HCC after HBsAg seroclearance was 4.8%. LC with excessive drinking and vertical infection were found to be risk factors for HCC in the HBsAg-NC group.

Conclusion: HCC surveillance should be continued after HBsAg seroclearance. An HBsAg-SCR < 1000 and its decrease in sequential testing are worth noting as predictive markers of HBsAg loss.

Keywords: HBeAg; HBsAg; Hepatitis B Surface antigen; Hepatitis B e antigen; Hepatitis B virus; Hepatocellular carcinoma; Liver cirrhosis; Seroconversion.

Figure 1

Signal-to-cutoff ratio of hepatitis B surface antigen was measured by qualitative assay and partially reflects the quantity of hepatitis B surface antigen in the serum. A: There was a log-linear correlation between the HBsAg-SCR and HBsAg-QNT; B: There was a good correlation with a linear drift curve between an HBsAg-SCR < 1000 and an HBsAg-QNT < 100 IU/mL (y = 0.0674x + 0.9902, R² = 0.916); C: HBsAg-QNT levels of greater than 200 IU/mL were not correlated with the HBsAg-SCR; D: Very high HBsAg titers of more than 10000 IU/mL were inversely correlated with the HBsAg-SCR, which was caused by a prozone effect. HBsAg-SCR: Signal-to-cutoff ratio of HBsAg; HBsAg-QNT: Quantity of HBsAg; HBsAg: Hepatitis B surface antigen.

Figure 2

Sequential changes in the signal-to-cutoff ratio of Hepatitis B surface antigen in the patients with negative conversion of Hepatitis B surface antigen during the follow-up period after registration. A: HBsAg-SCRs in the patients with HBsAg-NC after 5 years post-entry; B: HBsAg-SCRs in the patients with HBsAg-NC before 5 years post-entry. HBsAg-SCR: Signal-to-cutoff ratio of HBsAg; HBsAg-NC: Negative conversion of HBsAg; HBsAg: Hepatitis B surface antigen.