The impact of HBV-DNA fluctuations on virus-specific CD8+ T cells in HBeAg+ chronic hepatitis B patients treated with a steroid and lamivudine.
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.
Gotto
J
J
Institute of Hepatology, Royal Free and University College of London Medical School, London, UK.
Webster
G J M
GJ
Brown
D
D
Jenkins
J
J
Dusheiko
G M
GM
Bertoletti
A
A
D000328:Adult; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004279:DNA, Viral / Q000097:blood*; D004359:Drug Therapy, Combination; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000188:drug therapy; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D004279:DNA, Viral; D018984:Epitopes, T-Lymphocyte; D005938:Glucocorticoids; D006513:Hepatitis B e Antigens; D010455:Peptides; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D011239:Prednisolone