title: HBsAg plasma level kinetics: a new role for an old marker as a therapy response predictor in vertically infected children on combination therapy.
abstract: 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-α (IFN-α) [5 responders (R = anti-HBs seroconversion) and 18 nonresponders (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(®) assay [log10 IU/mL]. Baseline liver HBV-DNA and cccDNA were quantified by real-time TaqMan PCR [log10 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.
authors.affiliation: Institute of Liver Studies and Paediatric Liver, GI & Nutrition Centre, King's College London School of Medicine at King's College Hospital, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Carey
authors.forename: M
authors.initials: M
authors.lastname: Bruce
authors.forename: M
authors.initials: M
authors.lastname: Horner
authors.forename: Y
authors.initials: Y
authors.lastname: Zen
authors.forename: L
authors.initials: L
authors.lastname: D'Antiga
authors.forename: S
authors.initials: S
authors.lastname: Bansal
authors.forename: D
authors.initials: D
authors.lastname: Vergani
authors.forename: G
authors.initials: G
authors.lastname: Mieli-Vergani
mesh_terms: D000293:Adolescent; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000032:analysis; D016903:Drug Monitoring / Q000379:methods*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D006514:Hepatitis B Surface Antigens / Q000032:analysis / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D008099:Liver / Q000821:virology; D008297:Male; D010949:Plasma / Q000737:chemistry; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D019259:Lamivudine
keywords: HBsAg levels; cccDNA; chronic hepatitis B; immunotolerant patients; precore mutations