Immunological predictors of different responses to combination therapy with interferon α and ribavirin in patients with chronic hepatitis C

Abstract

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.

Haplotype-taggingRANTES gene variants influence response to antiviral therapy in chronic hepatitis C

“…13 Therefore, the higher frequencies of RANTES haplotypes 3 and 4 in patients with a negative outcome of antiviral therapy fit perfectly with a genetically determined down-regulation of T helper 1 lymphocyte-associated responses in these patients. 10,11 This would reduce the overall chances for successful HCV clearance, as observed in the present study. In contrast, the R2 haplotype (harboring the -403 A but not the Int1.1 C allele) was more prevalent in responders compared with nonresponders, which is consistent with in vitro transient transfection studies reporting a mean fourfold higher constitutive transcriptional activity of the RANTES promoter carrying the -403 A allele.…”

“…32 In recent years, several lines of evidence have indicated that patients who either spontaneously clear HCV RNA or respond successfully to antiviral therapy display a predominantly proinflammatory (T helper 1 lymphocyteassociated) cytokine profile. 10,11 RANTES specifically binds to the chemokine receptor CCR5 and attracts proinflammatory CD4 ϩ T helper 1 lymphocytes. 9 Interestingly, the CCR5 ⌬32 mutation leads to a decreased expression of the functional CCR5 protein 7 and has been linked to a negative outcome of interferon monotherapy in HCV infection, 8 although these results have not yet been reproduced for combination therapies.…”

“…6 Interestingly, a 32-base pair deletion in the gene of the CC chemokine receptor 5 (CCR5 ⌬32), which results in decreased receptor expression, 7 has recently been linked to a negative response to interferon monotherapy in hepatitis C. 8 Because the CCR5 ligand RANTES preferentially attracts T helper 1 lymphocytes, 9 RANTES might also be associated with treatment response to antiviral therapy, which is thought to depend on a sufficient proinflammatory cytokine response. 10,11 The human RANTES gene spans 8.5 kb on chromosome 17q11-q12 and has the characteristic three exons/ two introns organization of the CC chemokine family. 12 Upon sequencing of the entire RANTES gene, seven single nucleotide polymorphisms (SNPs) were identified using a DNA panel of Caucasian and African individuals.…”

Orally administered Kampo medicine, Juzen-taiho-to, ameliorates anemia during interferon plus ribavirin therapy in patients with chronic hepatitis C

“…Alternatively, TJ-48 has been shown to affect T-cellmediated immunity. 5 The efficacy of IFN/Rib therapy for chronic hepatitis C is associated with a vigorous peripheral blood T-helper (Th)1 cell response, 7 indicating the possibility that administration of TJ-48 prevents anemia via immunological mechanisms. The findings presented here indicate that, although the anemia observed during IFN/Rib therapy, which is likely to be hemolytic, is reversible, the concurrent administration of TJ-48 ameliorates the decreases in hemoglobin levels in patients treated with interferon and ribavirin, contributing to the success of this combination therapy.…”

Combination therapy with interferon-α and ribavirin as immunomodulators in patients with chronic hepatitis C

“…In this issue of the Journal of Gastroenterology, Amarra and colleagues 19 report that the efficacy of combination therapy with IFN-α and ribavirin for CHC is associated with a vigorous response of peripheral blood Th1 cells, whereas a weak CTL response at the end of the therapy might predict a subsequent relapse of the disease. The production of Th1-type cytokines (IFN-γ, IL-2, and tumor necrosis factor alpha [TNF-α]) at the end of the treatment was significantly higher than the baseline values in complete responders.…”