RESUMO
Combination therapy comprising pegylated interferon-alpha (PegIFNα) and ribavirin (RBV) has been the standard of care for the chronic hepatitis C patients for more than a decade. Recently, direct antiviral agents show better efficacy, tolerance, and shorter treatment duration. However, the prohibitive costs of the regimens limit their use in developing countries where most of the HCV infection exists. Optimizing the treatment and understanding the host- and virus-factors associated with viral clearance were necessary for individualizing therapy to maximize sustained virologic response. To explore individualized antiviral strategies with PegIFNα-2a/IFNα-2b plus ribavirin for CHC patients, and to clarify predictive factors for virological response. A cohort of 314 patients were included in this open-label, prospective clinical trial, which received individualized doses of PegIFNα-2a or IFNα-2b combined with RBV according to body weight, disease status and complications, with the duration of 44 weeks after HCV RNA undetectable. All the IL-28B (rs8099917), IL-17A (rs8193036), IL-17B (rs2275913) and PD-1.1 SNPs were genotyped using the TaqMan system. The sustained virological response (SVR) in PegIFNα-2a group was significantly higher than that in IFNα-2b (85.8% vs 75.0%, P = 0.034), especially in HCV genotype 1 (84.0% vs 64.3%, P = 0.022). However, no significant differences were found in rapid virological response (RVR), complete early virological response (cEVR) and SVR between PegIFNα-2a and IFNα-2b according to different doses, respectively. The genotype frequency of IL-28B TT in patients with cEVR, SVR was higher than that in non-responsed patients (93.8% vs 78.1%, χ(2) = 7.827, P = 0.005; 95.9% vs 80.4%, χ(2) = 9.394, P = 0.002). No significant correlation between the genotype distribution of IL-17A, IL-17B and PD-1.1 with virological response. Individualized regimens of PegIFNα-2a/RBV and IFNα-2b/RBV could achieve satisfied virological response in Chinese HCV patients. The IL-28B (rs8099917) TT genotype is a clinical usefully marker for cEVR and SVR.
RESUMO
OBJECTIVE: To investigate the association of single nucleotide polymorphisms (SNPs) in the interleukin 17 (IL-17) gene and serum protein levels in patients with chronic hepatitis C virus (HCV) infection. METHODS: A total of 228 patients with chronic HCV infection and 81 healthy controls were enrolled in the study. The frequencies of IL-17 rs8193036 and rs2275913 polymorphisms were detected by the TaqMan SNP genotyping assay. Serum levels of IL-17 protein were detected by ELISA. Pairwise comparisons were made by the Chi-square test, and the significance of between-group differences was assessed by the Student's t-test with P less than 0.05. RESULTS: The patients with chronic HCV infection and the healthy controls showed similar frequencies of the rs8193036 C/T allele (x2 = 1.428, P = 0.232) and the rs2275913 A/G allele (x2 = 0.106, P = 0.744). In addition, the two groups showed similar distribution of the rs8193036 CC (chronic HCV infection: 46.49% vs. healthy controls: 41.98%), CT (45.61% vs. 44.44%) and TT (7.89% vs. 13.58%) genotypes (x2 = 2.346, P = 0.309), and of the rs2275913 AA (16.23% vs. 13.58%), AG (48.25% vs. 50.62%) and GG (35.53% vs. 35.80%) genotypes (x2 = 0.340, P = 0.844). Subgroup analysis of chronic HCV infection patients stratified according to HCV genotypes 1 and 2 showed no differences in the distribution of rs8193036 and rs2275913 alleles (x2 = 1.127, P = 0.288; x2 = 1.088, P = 0.297) and genotypes (x2 = 2.825, P = 0.246; x2 = 0.970, P = 0.616). However, the chronic HCV infection group did show significantly higher levels of serum IL-17 than the controls (97.67+/-39.68 vs. 71.60+/-19.78 pg/ml, t = 2.414, P = 0.033). CONCLUSION: Chronic HCV infection is associated with increased serum IL-17; however, the IL-17 polymorphisms rs8193036 and rs2275913 were not associated with chronic HCV infection susceptibility in this study's Chinese cohort.