Hepatitis B virus-specific T cell response in chronic hepatitis B patients treated with lamivudine and interferon-alpha.
OBJECTIVE
The goal of the present study was to assess the impact combination antiviral therapy has on immune responses in chronic hepatitis B.


METHODS
T cell responses were studied in 16 chronically hepatitis B virus (HBV)-infected patients treated with sequential, partially overlapping, lamivudine-interferon (IFN)-alpha combination therapy.


RESULTS
HBcAg-specific lymphoproliferative response (LPR) was transiently detected in four of five patients who achieved virus suppression (HBV DNA < 10(4) genome equivalents/ml) at end of dual therapy, and then reverted to pre-treatment viral load after therapy discontinuation. In contrast, no significant HBcAg-specific LPR was detected in 8 patients who did not attain profound HBV suppression, as well as in three patients who experienced no HBV DNA rebound after therapy discontinuation.


CONCLUSIONS
This pilot study suggests that restored viral replication after pharmacological suppression drives the immune response to HBV in chronically infected patients. Further characterization of the adaptive immunity and its regulatory mechanisms at time of therapy discontinuation appears therefore necessary in controlled trials.
Institute of Virology, Erasmus Medical Center, Rotterdam, The Netherlands. o.pontesilli@erasmusmc.nl
Oscar
O
Pontesilli
Andeltje B
AB
van Nunen
Debby
D
van Riel
Patrizia
P
Carotenuto
Hubert G
HG
Niesters
Fons G
FG
Uytdehaag
Robert A
RA
De Man
Albert D
AD
Osterhaus
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D006512:Hepatitis B Core Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D019259:Lamivudine / Q000008:administration & dosage*; D008875:Middle Aged; D010865:Pilot Projects; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D016898:Interferon-alpha; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine