HBsAg plasma level kinetics: a new role for an old marker as a therapy response predictor in vertically infected children on combination therapy

We aimed to investigate the ability of HBsAg plasma level kinetics to predict therapy response by studying 23 children with infancy-acquired chronic hepatitis B (CHB) during combination sequential therapy with lead-in lamivudine (LAM) and add-on interferon-alpha (IFN-alpha) [5 responders (R = anti-HBs seroconversion) and 18 non-responders (NR)] and to assess their relationship with pretreatment intrahepatic HBV-DNA and cccDNA and HBsAg and HBcAg liver expression. Plasma HBsAg levels were measured in samples before (treatment week 0 = TW0), during (TW9, TW28, TW52) and after (follow-up week = FUW24) therapy by Abbott ARCHITECT (R) assay [log(10)IU/mL]. Baseline liver HBV-DNA and cccDNA were quantified by real-time TaqMan PCR [log(10)copies/ng genomic DNA]. HBsAg and HBcAg liver expression was evaluated by immunostaining of formalin-fixed, paraffin-embedded specimens [number of positive cells/1000 hepatocytes]. All results are presented as medians. Plasma: at baseline, on-treatment and during follow-up, HBsAg levels were lower in R than NR (TW0: 4.36 vs 4.75; TW28: 2.44 vs 4.35; TW52: 0 vs 4.08 and FUW24: 0.17 vs 4.35, all P < 0.05). Liver: baseline HBV-DNA (3.82 vs 4.71, P = 0.16) and cccDNA (1.98 vs 2.26, P = 0.18) tended to be lower in R than NR, HBsAg expression was lower in R than NR (0.5 vs 4.7, P = 0.03), and HBcAg expression was similar between R and NR. There were positive correlations between plasma HBsAg levels and liver HBV-DNA (r = 0.44, P = 0.04), cccDNA (r = 0.41, P = 0.04) and HBsAg liver expression (r = 0.38, P = 0.05). Lower baseline HBsAg plasma levels, lower HBsAg expression in liver and on-treatment decline of plasma HBsAg levels heralds HBsAg clearance and response to treatment in tolerant children with CHB.