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

I Carey, M Bruce, M Horner, Y Zen, L D'Antiga, S Bansal, D Vergani, G Mieli-Vergani

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3 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)441-452
Number of pages12
JournalJournal of Viral Hepatitis
Volume22
Issue number4
Early online date3 Oct 2014
DOIs
Publication statusPublished - Apr 2015

Keywords

  • Adolescent
  • Antiviral Agents/therapeutic use
  • Biomarkers/blood
  • Child
  • Child, Preschool
  • DNA, Viral/analysis
  • Drug Monitoring/methods
  • Drug Therapy, Combination/methods
  • Female
  • Gene Expression Profiling
  • Hepatitis B Surface Antigens/analysis
  • Hepatitis B, Chronic/drug therapy
  • Humans
  • Immunohistochemistry
  • Interferon-alpha/therapeutic use
  • Lamivudine/therapeutic use
  • Liver/virology
  • Male
  • Plasma/chemistry
  • Prognosis
  • Treatment Outcome

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