Immunological predictors of different responses to combination therapy with interferon alpha and ribavirin in patients with chronic hepatitis C.
BACKGROUND
This study aimed to investigate peripheral blood CD4+ T-helper (Th) and CD8+ cytotoxic T-lymphocyte (CTL) responses to combination treatment with interferon (IFN) alpha and ribavirin in 59 patients with chronic hepatitis C, and to correlate the results with the therapy outcome.


METHODS
The expression of activation molecules on the surface of CD8+ T cells and cytokine production by in-vitro activated CTLs and Th lymphocytes were examined before and at the end of the therapy, using flow cytometry.


RESULTS
There were 36 complete responders to the treatment and 23 transient responders who relapsed after withdrawal of the therapy. A significant increase in the production of Th1-type cytokines [IFNgamma, interleukin 2 (IL2), and tumor necrosis factor-alpha (TNFalpha)] was found at the end of the treatment in complete responders compared with baseline values (P < 0.001). In contrast, transient responders had a marked decrease in the percentage of activated CD8+ T cells expressing CD28 or HLA-DR costimulatory molecules in peripheral blood, and a lower production of TNFalpha by CTLs and Th cells at the end of the therapy with respect to pretreatment values (P < 0.001).


CONCLUSIONS
The efficacy of IFNalpha and ribavirin combination therapy for chronic hepatitis C is associated with a vigorous response of peripheral blood Th1 cells, whereas weak CTL responses at the end of the therapy might predict a further relapse of the disease.
Amaraa
Ravdan
R
Institute of Microbiology and Clinical Immunology, First Medical Faculty, Charles University, Karlovo nam 32, Prague 2 Cz-12111, Czech Republic.
Mareckova
Helena
H
Urbanek
Petr
P
Fucikova
Terezie
T
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D012254:Ribavirin / Q000008:administration & dosage*
D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin