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Abstract：
To investigate associations between inosine triphosphatase (ITPA) gene polymorphisms and long-term outcomes among chronic hepatitis C (CHC) patients in Northeast China treated with Peg-interferon (IFN)/ribavirin (RBV). CHC patients who received Peg-IFN-2a/RBV treatment during between 2011 and 2013 at 5 hepatitis centers in Northeast China were enrolled. ITPA single nucleotide polymorphisms rs1127354 and rs7270101 from all patients were detected and their associations with 5-year outcomes were analyzed. A total of 635 patients, including 421 infected with hepatitis C virus (HCV) genotype 1 and 214 infected with non-genotype 1 were included. No significant differences were observed in the distribution frequencies of ITPA rs1127354 variants and ITPase activity between patients with HCV genotype 1 and non-genotype 1. In patients who received more than 80% of the planned RBV dose, the 5-year virological response rate and the improvement in liver fibrosis were higher in those with ITPA rs1127354 non-CC with ITPase activity <25% compared with these outcomes in patients with ITPA rs1127354 CC with 100% ITPase activity. Multiple regression analysis revealed that HCV genotype non-1, low baseline HCV ribose nucleic acid (RNA) levels (≤4 × 105 IU/mL), interleukin-28B rs12979860 CC genotype, low baseline liver fibrosis (Fibroscan 0-2), and ITPA rs1127354 non-CC genotype were independent predictors for a high long-term virological response rate, whereas interleukin-28B rs12979860 CC genotype, ITPA rs1127354 non-CC genotype, and low baseline liver fibrosis were independent predictors for improvement of liver fibrosis. ITPA rs1127354 polymorphisms is predictors of long-term outcomes in CHC patients treated with Peg-IFN/RBV.
摘要：
探讨应用聚乙二醇干扰素(IFN)/利巴韦林(RBV)治疗的中国东北地区慢性丙型肝炎(CHC)患者中肌苷三磷酸酶(ITPA)基因多态性与长期预后的关系。在2011年至2013年期间在中国东北5个肝炎中心接受PEG-IFN-2a/RBV治疗的CHC患者被招募。检测所有患者的ITPA单核苷酸多态性rs1127354和rs7270101，并分析其与5年预后的关系。总共635名患者，包括421例感染丙型肝炎病毒（HCV）基因型1和214例感染非基因型1。在HCV基因型1和非基因型1的患者之间，ITPArs1127354变体的分布频率和ITPase活性没有观察到显着差异。在接受计划RBV剂量80％以上的患者中，与ITPase活性为100%的ITPArs1127354CC患者的这些结局相比,ITPArs1127354非CC患者的5年病毒学应答率和肝纤维化改善更高.多元回归分析显示，HCV基因型non-1，低基线HCV核糖核酸（RNA）水平（≤4×105IU/mL），白细胞介素-28Brs12979860CC基因型，低基线肝纤维化（Fibroscan0-2），和ITPArs1127354非CC基因型是高长期病毒学应答率的独立预测因子，而白细胞介素-28Brs12979860CC基因型，ITPArs1127354非CC基因型，低基线肝纤维化是肝纤维化改善的独立预测因子。ITPArs1127354多态性是PEG-IFN/RBV治疗CHC患者长期预后的预测因子。
