Sustained virological response to peginterferon plus ribavirin in chronic hepatitis C genotype 1 patients is associated with a persistent Th1 immune response.
BACKGROUND
An impairment of cellular immune response may contribute to the persistency of hepatitis C virus infection.


OBJECTIVE
To analyse the Th1/Th2 cytokine profile in peripheral blood CD4(+) and CD8(+) T cells from patients with chronic hepatitis C (CHC) during treatment with pegylated interferon-alpha2a plus ribavirin and to correlate the Th1/Th2 balance with virological response (SVR).


METHODS
Prospective longitudinal study: 44 naïve genotype 1 CHC patients received PEG-IFNalpha2a plus ribavirin for 48 weeks: 26 (59.1%) achieved a SVR, 13 relapsed (29.5%) and 5 (11.4%) were non-responders. Sixteen healthy controls were analysed. The production of IL-4, IFNgamma and TNFalpha by CD4(+) and CD8(+) T cells was measured using flow cytometry, both in resting and phorbol-ester-stimulated cells.


RESULTS
First three months of treatment: the synthesis of TNFalpha by phorbol-ester-stimulated-CD4(+) T cells was higher in patients with SVR (P < 0.01). At the end of treatment, SVR was associated with higher intracellular expression of IFNgamma by stimulated-CD4(+) and CD8(+) T cells (P < 0.05). At the end of follow-up, a higher intracellular expression of IFNgamma by CD4(+) T cells was associated with a SVR.


CONCLUSIONS
A Th1-type immune response was associated with achievement of a SVR, as indicated by the persistent elevation of intracellular IFNgamma and TNFalpha.
Trapero-Marugán
M
M
Gastroenterology and Hepatology Service, Hospital Universitario de La Princesa, Madrid, Spain.
García-Buey
L
L
Muñoz
C
C
Quintana
N E
NE
Moreno-Monteagudo
J A
JA
Borque
M J
MJ
Fernández
M J
MJ
Salvanés
F R
FR
Medina
J
J
Moreno-Otero
R
R
D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D004359:Drug Therapy, Combination; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008137:Longitudinal Studies; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D018417:Th1 Cells / Q000276:immunology; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a