Early immune-mediated response to ribavirin combined with IFN in patients with chronic hepatitis C.
ABSTRACT This study was to investigate the immunomodulatory effects of ribavirin combined with interferon (IFN)-alpha 2b (R+IFN) compared with consensus IFN monotherapy (IFN-Con) in chronic hepatitis C (CHC) patients.
Thirty-four adult patients with biopsy-proven CHC, who were infected with HCV genotype 2a or 2b, were studied. A 24-week regimen of IFN-alpha 2b (6MU daily for 2 weeks followed by 6MU tiw for 22 weeks) and ribavirin (600-800mg/day for 24 weeks) was given to 17 patients. The other 17 patients were treated with a 24-week regimen of IFN-Con (18MU daily for 2 weeks followed by 18MU tiw for 22 weeks). Flow cytometric determination of cytoplasmic IFN-gamma and IL-4 expression in peripheral blood CD4+ T cells was performed, and the percentage of IFN-gamma+ and IL-4- (Th1), IFN-gamma- and IL-4+ (Th2) cells were calculated before and 3, 7, 14, and 28 days after the start of therapy.
In the R+IFN group, the percentage of Th1 cell peaked on day 3, and then decreased to near baseline by day 14, while the percentage of Th2 cell did not change. In the IFN-Con group, the percentage of Th1 cell peaked on day 14 and the percentage of Th2 cell peaked on day 3, and then decreased to near baseline by day 14.
Our results suggest that ribavirin induces an early immune response by peripheral blood CD4+ T cells in CHC patients.
Inflammation and Regeneration 01/2009; 29(2):135-141. DOI:10.2492/inflammregen.29.135
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ABSTRACT: BACKGROUND/AIM: The number of amino acid (AA) mutations in the interferon sensitivity determining region (ISDR) of NS5A is reported to affect the response to interferon (IFN) therapy in patients with chronic hepatitis C (CHC). The aim of this study was to clarify whether host immunity is influenced by the number of AA mutations in the ISDR. PATIENTS AND METHODS: Subjects included 44 patients with CHC infected with genotype 1b and high viral load. The number of AA mutations in the ISDR was retrospectively determined using stored serum samples taken immediately before starting therapy. All patients received IFN-alpha 2b or pegylated-IFN (PEG-IFN)-alpha 2b and ribavirin. When serum hepatitis C virus-ribonucleic acid (HCV-RNA) was negative at 4 or 12 weeks after starting therapy, the patient was defined as having rapid viral response (RVR) or early viral response (EVR), respectively. CD4(+) T cell (Th1 or Th2) in peripheral blood (PB) before and until day 56 of treatment was analyzed. RESULTS: Rates of RVR and EVR were 0 (0/21) and 14% (3/21), respectively, in patients with one or fewer AA mutations in the ISDR (ISDR0-1), and 30 (7/23), and 74% (17/23), respectively, with two or more AA mutations in the ISDR (ISDR > 2). Although the percentage of PB Th1 cells did not differ between the two groups during the study period, the percentage of PB Th2 cells was significantly lower in the ISDR0-1 group than in the ISDR > 2 group at baseline and on days 3, 7, 14, and 28 of treatment. CONCLUSION: The number of AA mutations in the ISDR influenced PB Th2 cells before and until day 28, and was associated with higher RVR and EVR rates.Hepatology International 08/2011; DOI:10.1007/s12072-011-9305-8 · 2.47 Impact Factor
Inflammation and Regeneration 01/2007; 27(3):187-193. DOI:10.2492/inflammregen.27.187