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HB s A g plasma level kinetics: a new role for an old marker as a therapy response predictor in vertically infected children on combination therapy
Author(s) -
Carey I.,
Bruce M.,
Horner M.,
Zen Y.,
D'Antiga L.,
Bansal S.,
Vergani D.,
MieliVergani G.
Publication year - 2015
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12316
Subject(s) - hbsag , cccdna , hbcag , medicine , taqman , hepatitis b , real time polymerase chain reaction , gastroenterology , immunology , combination therapy , seroconversion , hepatitis b virus , microbiology and biotechnology , biology , antibody , virus , gene , biochemistry
Summary We aimed to investigate the ability of HBsA g 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‐ HB s seroconversion) and 18 nonresponders ( NR )] and to assess their relationship with pretreatment intrahepatic HBV ‐ DNA and ccc DNA and HB s A g and HB c A g liver expression. Plasma HB s A g levels were measured in samples before (treatment week 0 = TW 0), during ( TW 9, TW 28, TW 52) and after (follow‐up week = FUW 24) therapy by A bbott ARCHITECT ® assay [log 10 IU / mL ]. Baseline liver HBV ‐ DNA and ccc DNA were quantified by real‐time T aq M an PCR [log 10 copies/ng genomic DNA ]. HB s A g and HB c A g 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, HBsA g levels were lower in R than NR ( TW 0: 4.36 vs 4.75; TW 28: 2.44 vs 4.35; TW 52: 0 vs 4.08 and FUW 24: 0.17 vs 4.35, all P < 0.05). Liver: baseline HBV ‐ DNA (3.82 vs 4.71, P = 0.16) and ccc DNA (1.98 vs 2.26, P = 0.18) tended to be lower in R than NR , HB s A g expression was lower in R than NR (0.5 vs 4.7, P = 0.03), and HB c A g expression was similar between R and NR . There were positive correlations between plasma HB s A g levels and liver HBV ‐ DNA ( r = 0.44, P = 0.04), ccc DNA ( r = 0.41, P = 0.04) and HB s A g liver expression ( r = 0.38, P = 0.05). Lower baseline HB s A g plasma levels, lower HB s A g expression in liver and on‐treatment decline of plasma HB s A g levels heralds HB s A g clearance and response to treatment in tolerant children with CHB .