Genomic diversity of the genotype 1b hepatitis C virus open reading frame is correlated with outcomes of combined pegylated-interferon/ribavirin therapy in patients with chronic hepatitis C from Henan Province

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To determine the role of hepatitis C virus (HCV) genotype 1 b genetic variation in the open reading frame for treatment outcomes of the pegylated-interferon/ribavirin (peg-IFN/RBV) combination therapy by examining patients from Henan Province with chronic hepatitis C (CHC). Thirty-seven treatment naive patients infected with HCV genotype 1b were included in the study. Prior to initiation of a 48-week course of peg-IFN/RBV therapy, peripheral blood was drawn for sequencing of the viral ORF 5'-half. Patients were assessed at the end of the 48 weeks of treatment and at a 6-month follow-up appointment. The patient data was stratified according to the status of sustained viral response (SVR) group and non-response (NR) and statistical analysis was performed to determine the correlation between detected genetic variations and treatment response status. Genetic variability in the ORF 5'-half was significantly higher among the individuals in the SVR group than among those of the NR group. Significant differences were found in the gene regions encoding p7, NS2 and NS3. For p7, the NR group had actual and expected frequencies of special mutation of 9.0 and 17.4 and total mutation of 77.0 and 68.6, while the SVR group had actual and expected frequencies of special mutation of 42.0 and 33.6 and total mutation of 124.0 and 132.4 (x2 =7.725, P =0.05). For NS2, the NR group had actual and expected frequencies of special mutation of 36.0 and 54.3 and total mutation of 270.0 and 251.7, while the SVR group had actual and expected frequencies of special mutation of 106.0 and 87.7 and total mutation of 388.0 and 406.3 (x2 = 12.16, P less than 0.01). For NS3, the NR group had actual and expected frequencies of special mutation of 49.0 and 53.4 and total mutation of 241.0 and 236.6, while the SVR group had actual and expected frequencies of special mutation of 81.0 and 76.6 and total mutation of 335.0 and 339.4 (x2 =6.745, P =0.043). The inter-patient genetic variations in the NS3 gene were concentrated in the protease domain. Furthermore, there was a strong correlation between HCV diversity in p7 and treatment outcome. The genetic data reported here provides strong support for the role of NS2, NS3 and p7 in antagonizing the peg-IFN/RBV response during the treatment of HCV infections. We conclude that higher inter-patient viral genetic diversity correlates with successful treatment and may modulate the efficacy of antiviral therapy in CHC patients of Henan.