Longitudinal profiles of highly sensitive hepatitis B surface antigen levels: re‐evaluation of HB sAg seroclearance

BACKGROUND & AIMS: Serologic profiles after hepatitis B surface antigen (HBsAg) seroclearance in chronic hepatitis B (CHB) have not been well-studied. METHODS: We employed a highly sensitive HBsAg (hs-HBsAg) assay (lower detection limit 0.5 mIU/ml), 100 times more sensitive than conventional HBsAg measurements. CHB patients achieving HBsAg seroclearance defined by conventional assays were followed up for serum hs-HBsAg, HBV DNA and antibody to HBsAg (anti-HBs) levels at 0 months, 6-12 months and 3-5 years after HBsAg seroclearance. Factors associated with hs-HBsAg detectability were determined. RESULTS: One hundred and nine patients were recruited; 94 (86.2%) were followed up to years 3-5; and 25 patients (22.9%) were on nucleoside analogue therapy for a median duration of 6.0 (range 1.5-12.7) years before HBsAg seroclearance. Detectable hs-HBsAg was noted in 88 (80.7%), 60 (55.0%) and 20 (21.3%) patients at 0 months, 6-12 months and 3-5 years respectively. At years 3-5, genotype B patients, when compared to genotype C patients, had a higher anti-HBs positive rate (63.2% and 41.1% respectively, P = 0.036). Serum anti-HBs positivity, when compared to persistent anti-HBs negativity, was associated with a lower rate of hs-HBsAg detection (7.4% and 40% respectively, P < 0.001). Multivariate analysis showed anti-HBs negativity at years 3-5 to be independently associated with persistently positive hs-HBsAg (P = 0.007, odds ratio 7.1, 95% confidence interval 1.7-29.3). CONCLUSION: Serum hs-HBsAg could detect HBsAg presence in a substantial proportion of CHB after HBsAg seroclearance defined by conventional assays, especially among anti-HBs negative individuals. Serum hs-HBsAg could potentially assist differentiating HBsAg-negative CHB from individuals with only past HBV exposure without carrier state.