Gotto, J; Webster, GJ; Brown, D; Jenkins, J; Dusheiko, GM; Bertoletti, A; (2006) The impact of HBV-DNA fluctuations on virus-specific CD8+ T cells in HBeAg+ chronic hepatitis B patients treated with a steroid and lamivudine. J Viral Hepat , 13 (6) 415 - 425. 10.1111/j.1365-2893.2005.00716.x.
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Restoration of anti-viral immune response may be a requisite for sustained virological response to treatment in chronic hepatitis B patients. Over a 13-month period, we examined the dynamics of hepatitis B virus (HBV)-specific CD8+ cells in six human leucocyte antigen (HLA)-A2+ hepatitis B e antigen (HBeAg)+ 'immunotolerant' chronic hepatitis B patients treated sequentially with corticosteroid and lamivudine. Our results show that the combination treatment did not result in a sustained restoration of anti-viral specific CD8+ cells in five of the six patients studied. However, HBV-specific CD8+ cells, despite being severely compromised, were not totally deleted. Paradoxically, steroid treatment was not associated with inhibition but with a minimal increase of the HBV-specific CD8 response, and we observed that nucleocapsid-specific CD8 responses were not rescued by stable and prolonged inhibition but became detectable after rapid rebounds of HBV replication. In most patients, the transient and minimal restoration of HBV-specific immunity was not associated with clinical benefits. Our results describe a dynamic relationship between HBV-specific CD8+ cells and HBV-DNA values, that could potentially be used for a better design of HBV treatment in HBeAg+ 'immunotolerant' chronic hepatitis B patients.
|Title:||The impact of HBV-DNA fluctuations on virus-specific CD8+ T cells in HBeAg+ chronic hepatitis B patients treated with a steroid and lamivudine.|
|Keywords:||Adult, Amino Acid Sequence, CD8-Positive T-Lymphocytes, DNA, Viral, Drug Therapy, Combination, Epitopes, T-Lymphocyte, Female, Glucocorticoids, Hepatitis B e Antigens, Hepatitis B virus, Hepatitis B, Chronic, Humans, Lamivudine, Male, Middle Aged, Molecular Sequence Data, Peptides, Prednisolone, Reverse Transcriptase Inhibitors, Treatment Outcome|
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