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Decline in intrahepatic ccc DNA and increase in immune cell reactivity after 12 weeks of antiviral treatment were associated with HB e A g loss
Author(s) -
Zheng Q.,
Zhu Y. Y.,
Chen J.,
Liu Y. R.,
You J.,
Dong J.,
Zeng D. W.,
Gao L. Y.,
Chen L. H.,
Jiang J. J.
Publication year - 2014
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.12261
Subject(s) - adefovir , hbeag , viral load , elispot , cccdna , immune system , immunology , medicine , hepatitis b virus , seroconversion , cd8 , virology , virus , hbsag , lamivudine
Summary Viral load reduction facilitates recovery of antiviral T‐cell responses. Dynamic alterations in intrahepatic viraemia clearance and immune cell reactivity during the early phase of nucleoside analogue ( NA ) therapy and the impact of these changes on HB eAg seroconversion are unknown. Fifteen HB eAg‐positive chronic hepatitis B ( CHB ) patients were treated with adefovir dipivoxil. T‐cell reactivity to HBV core and surface antigens were tested using ELISPOT assay from baseline to week 48 post‐treatment (at 4‐week intervals). Before and at week 12 of treatment, paired liver biopsies were analysed for intrahepatic HBV ‐ DNA and ccc DNA via real‐time fluorescent PCR . In situ detection of CD 4 + , CD 8 + T cells and NK cells was analysed by immunohistochemistry. With viral load reduction, HBV ‐specific IFN ‐ γ ‐producing CD 4 + T cells in patients with HB eAg loss were greatly enhanced and reached the highest level at week 12, with further increase observed between week 36 and week 48. After 12 weeks of treatment, total intrahepatic HBV ‐ DNA and ccc DNA had significantly decreased; however, there was no difference in the viral loads or extent of reduction between patients with and without HB eAg loss. Paralleling reduction in viral load, intrahepatic CD 8 + T lymphocytes increased in patients with HB eAg loss compared with baseline values. Only one patient without HB eAg loss exhibited similar results. Increased immune cells were observed in certain patients along with reduced hepatic viral loads during the second phase of HBV ‐ DNA decline, which could promote the recovery of antiviral immunity and facilitate HB eAg loss.