T-cell responses at baseline and during therapy with peginterferon-alpha and ribavirin are not associated with outcome in chronic hepatitis C infected patients.
BACKGROUND
Since the association between hepatitis C virus (HCV)-specific T-cell responses both pre-treatment and during interferon-alpha based therapy and viral clearance is unresolved, a combined analysis of distinctive T-cell characteristics (proliferation and interferon-gamma production) is important to clarify this issue.


METHODS
Peripheral blood mononuclear cells (PBMC) collected in 22 chronic HCV infected patients at pre-treatment and at week 4 during pegIFN-alpha/ribavirin therapy, were stimulated with overlapping peptide pools in a [3H]-thymidine assay, an interferon-gamma-ELISA, and a sensitive 12-day T-cell expansion assay.


RESULTS
Compared to the [3H]-thymidine proliferation and interferon-gamma secretion assays, the 12-day T-cell expansion assay was more sensitive in detecting T-cell responses. No significant association was demonstrated between pre-treatment HCV-specific CD4+ or CD8+ T-cell responses and either a sustained virological response (SVR) or a rapid virological response (RVR). However, a skewing of individual responses towards the non-structural antigens was observed. During pegIFN-alpha/ribavirin therapy, HCV-specific CD4+ and CD8+ T-cells declined similarly in both SVR/RVR and non-SVR/non-RVR patients.


CONCLUSIONS
No correlation was found between the magnitude of pre-treatment HCV-specific T-cell responses and the outcome of pegIFN-alpha/ribavirin therapy in terms of SVR and RVR. Moreover, the magnitude of HCV-specific T-cell responses declined in all patients early during treatment.
Arends
Joop E
JE
Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Heidelberglaan 100, P.O. Box 85500, 3508 GA Utrecht, Netherlands. j.e.arends@umcutrecht.nl
Claassen
Mark A A
MA
van den Berg
Charlotte H S B
CH
Nanlohy
Nening M
NM
van Erpecum
Karel J
KJ
Baak
Bert C
BC
Hoepelman
Andy I M
AI
Boonstra
Andre
A
van Baarle
Debbie
D
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D007371:Interferon-gamma; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a