Determinants of spontaneous surface antigen loss in hepatitis B e antigen-negative patients with a low viral load

Abstract

Loss of hepatitis B surface antigen (HBsAg) usually indicates the cure of hepatitis B virus (HBV) infection. In spontaneous hepatitis B e antigen (HBeAg) seroconverters, lower serum HBsAg and HBV DNA levels have been shown to be associated with HBsAg loss over time. However, little is known about their impacts on HBsAg loss in HBeAg-negative patients with limited viral replication. A total of 688 HBeAg-negative patients with baseline serum HBV DNA levels <2000 IU/mL were enrolled in Taiwan. The relationships of HBsAg and HBV DNA levels with subsequent HBsAg loss were investigated. In a mean follow-up of 11.6 years, the average annual rate of HBsAg loss was 1.6%. Baseline HBsAg and HBV DNA levels were inversely associated with subsequent HBsAg loss. When compared to patients who had HBsAg levels >1000 IU/mL, the rates of HBsAg loss were significantly higher in patients with HBsAg levels of 100-999, 10-99, and <10 IU/mL, with hazard ratios of 2.5 (95% confidence interval [CI], 1.6-4.0), 2.8 (95% CI, 1.6-5.0), and 13.2 (95% CI, 8.1-21.5), respectively. Multivariate analysis showed that HBsAg level, but not HBV DNA, remained as an independent factor. The adjusted hazard ratio of HBsAg loss was 13.2 (95% CI, 7.8-22.1) for HBsAg level <10 versus !1000 IU/mL. When compared to HBV DNA level by receiver operating characteristic curve analysis, HBsAg level served as a better predictor of both 5-year and 10-year HBsAg loss. Conclusion: In HBeAgnegative patients with HBV genotype B or C infection who have HBV DNA level <2000 IU/mL, HBsAg level <10 IU/mL is the strongest predictor of HBsAg loss. (HEPATOLOGY 2012;55:68-76) H epatitis B virus (HBV) infection is a global health problem, resulting in more than one million deaths per year. 1 Patients with chronic HBV infection are at increased risk of developing cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). [1][2][3] It is estimated that in HBV carriers who acquire the virus early in life, the lifetime risk of developing these complications is 25%-40%. 3,4 The REVEAL-HBV (Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer HBV) Study has indicated that in patients with chronic HBV infection, HBV DNA level is a major driver of disease progression. 5,6 Of particular note is that patients with serum HBV DNA levels !2000 IU/mL start to have an increased risk of developing adverse outcomes, including hepatitis, cirrhosis, HCC, and liver-related death. [5][6][7][8] In contrast, those individuals with HBV DNA levels <2000 IU/mL have a higher likelihood of becoming inactive carriers, and some clear hepatitis B surface antigen (HBsAg) during the follow-up, 9,10

Serum hepatitis B surface antigen levels help predict disease progression in patients with low hepatitis B virus loads

“…HBsAg levels were quantified using the Architect HBsAg QT assay (Abbott Laboratories, Abbott Park, IL) according to the manufacturer's instructions. 12,19,20 The detection range of the Architect assay is 0.05-250 IU/mL; if the HBsAg level was found to be higher than 250 IU/mL, the samples were diluted to 1:100 to 1:1,000 to obtain a reading within the calibration curve range.…”

Higher lifetime chance of spontaneous surface antigen loss in hepatitis B carriers with genotype C infection

“…4 Both factors are closely related with risk of HCC and chance of HBsAg clearance. [6][7][8][9] In addition to viral activity, HBV genotypes and mutants are also important determinants for disease progression in HBV carriers. [10][11][12] Patients with HBV genotype C infection are shown to carry a higher risk of HCC development than those with genotype B infection.…”

“…To address these interesting and important issues, we conducted a large cohort study with a long-term followup. 7,8,14,15 In the present study, we first determined viral genomic factors and analysed their relationships with HBsAg loss. We then performed sensitivity analysis to test whether the correlation between HBV genotype and HBsAg loss still held true in the whole cohort of HBsAg carriers.…”

Evaluation of changes of serum hepatitis B surface antigen from a different perspective

“…Thus, HBsAg monitoring can be used as a sign of HBV reactivation to determine the risk of disease activity [4,5] . In HBeAg-negative patients who have HBV DNA levels < 2000 IU/mL, HBsAg level < 10 IU/mL is the strongest predictor of HBsAg loss [6] . During the antiviral therapy, monitoring serum HBsAg levels dynamically may have high value for prediction of sustained virological response and HBsAg clearance [7][8][9][10] .…”