Premium
Impact of complete inhibition of viral replication on the cellular immune response in chronic hepatitis B virus infection
Author(s) -
Marinos G,
Naoumov N V,
Williams R
Publication year - 1996
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510240503
Subject(s) - lamivudine , hbcag , hepatitis b virus , hbeag , immunology , virology , medicine , viral replication , virus , nucleoside analogue , interferon , hepatitis b , interferon alfa , alpha interferon , biology , nucleoside , hbsag , biochemistry
Abstract Interferon alfa (IFN‐α) treatment is effective in only a proportion of patients with chronic hepatitis B virus (HBV) infection. The mechanisms for therapeutic failure remain unknown but high levels of HBV replication are known to inhibit the immunopotentiating effects of IFN‐α. In nine patients with chronic hepatitis B not responding to IFN‐α monotherapy, we determined the virus‐specific T‐helper‐cell responses during two consecutive therapeutic regimens: IFN‐α alone and IFN‐α in combination with a new potent inhibitor of HBV replication, lamivudine. By comparing the results obtained during the initial IFN‐α monotherapy to those during the combination treatment, it was investigated whether complete inhibition of virus replication will enhance the interferon‐induced immunoreactivity to HBV. Despite the rapid reduction to undetectable serum HBV DNA in all nine patients during the combination treatment, none sustained permanent hepatitis B e antigen (HBeAg) clearance during subsequent 12‐month follow‐up. HLA class II‐restricted T‐helper‐cell responses to hepatitis B core antigen (HBcAg) showed no difference during IFN‐α monotherapy and during the combination of lamivudine plus IFN‐α. In contrast, a delayed T‐cell activation occurred after a rebound in serum HBV DNA postcombination treatment, which lead to increased hepatocytolysis. These findings suggest that the profound inhibition of HBV replication by a nucleoside analogue does not restore the impaired virus‐specific T‐cell response in chronic HBV infection.