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Abstract：
BACKGROUND: Globally, 80 million people are suffering from chronic Hepatitis C virus (HCV) infection. Sofosbuvir ribavirin-based anti-HCV therapy is associated with anemia and other adverse effects. Polymorphisms of Inosine triphosphatase (ITPA) gene may cause functional impairment in the Inosine triphosphate pyrophosphatase enzyme, resulting in enhanced sustained viral response (SVR) and protection from ribavirin-associated anemia in patients on therapy. The study objective was to investigate the effect of Inosine triphosphatase gene polymorphism on SVR achievement, hemoglobin decline and ribavirin dose reduction in patients on therapy.
METHODS: This prospective cohort study was of 170 hepatitis C infected patients received 6-month sofosbuvir ribavirin therapy. Patient viral load, reduction in ribavirin amount, liver function test, and complete blood count were noted monthly. Inosine triphosphatase variants rs1127354 and rs7270101 were assessed through the restriction fragment length polymorphism and confirmed using Sanger sequencing. The impact of polymorphism on cumulative reduction of ribavirin, and anti-HCV therapy outcome were studied.
RESULTS: A total of 74.3% of patients had ITPA rs1127354 CC genotype, 25.7% were CA and AA 0%. The frequency of ITPA genotype rs7270101-AA was 95%, AC 5%, and CC was 0%. ITPA rs1127354-CA had a notably positive impact on SVR achievement with a zero-relapse rate. ITPA rs1127354-CA genotype was significantly (P ˂0.05) protective against ≥ 2 g/dl Hb reduction from baseline to 1st, 2nd and 6th months of therapy. During treatment, Hb reduction ≥ 10 g/dl was frequently observed in rs1127354-CC genotype and rs7270101-AA genotype patients. Ribavirin dose reduction was significantly (P ˂0.05) high in rs1127354-CC genotype as compared to genotype CA whereas no significant difference was observed in ribavirin dose reduction in rs7270101 AA and non-AA genotype. Patient baseline characteristics such as age, body mass index, rs1127354-CC genotype, and baseline Hb were significantly associated with significant Hb reduction.
CONCLUSIONS: Pretreatment evaluation of ITPA polymorphism can be a diagnostic tool to find out patients at risk of anemia and improve treatment adherence. ITPA genotype rs1127354-CA contributes to improved compliance with ribavirin dose and protects against hemoglobin decline in HCV patients while taking ribavirin-based therapy. However, ITPA rs1127354, rs7270101 polymorphism have no significant impact on SVR achievement.
METHODS: This prospective cohort study was of 170 hepatitis C infected patients received 6-month sofosbuvir ribavirin therapy. Patient viral load, reduction in ribavirin amount, liver function test, and complete blood count were noted monthly. Inosine triphosphatase variants rs1127354 and rs7270101 were assessed through the restriction fragment length polymorphism and confirmed using Sanger sequencing. The impact of polymorphism on cumulative reduction of ribavirin, and anti-HCV therapy outcome were studied.
RESULTS: A total of 74.3% of patients had ITPA rs1127354 CC genotype, 25.7% were CA and AA 0%. The frequency of ITPA genotype rs7270101-AA was 95%, AC 5%, and CC was 0%. ITPA rs1127354-CA had a notably positive impact on SVR achievement with a zero-relapse rate. ITPA rs1127354-CA genotype was significantly (P ˂0.05) protective against ≥ 2 g/dl Hb reduction from baseline to 1st, 2nd and 6th months of therapy. During treatment, Hb reduction ≥ 10 g/dl was frequently observed in rs1127354-CC genotype and rs7270101-AA genotype patients. Ribavirin dose reduction was significantly (P ˂0.05) high in rs1127354-CC genotype as compared to genotype CA whereas no significant difference was observed in ribavirin dose reduction in rs7270101 AA and non-AA genotype. Patient baseline characteristics such as age, body mass index, rs1127354-CC genotype, and baseline Hb were significantly associated with significant Hb reduction.
CONCLUSIONS: Pretreatment evaluation of ITPA polymorphism can be a diagnostic tool to find out patients at risk of anemia and improve treatment adherence. ITPA genotype rs1127354-CA contributes to improved compliance with ribavirin dose and protects against hemoglobin decline in HCV patients while taking ribavirin-based therapy. However, ITPA rs1127354, rs7270101 polymorphism have no significant impact on SVR achievement.
摘要：
背景：在全球范围内，8000万人患有慢性丙型肝炎病毒（HCV）感染。基于索非布韦利巴韦林的抗HCV治疗与贫血和其他不良反应有关。肌苷三磷酸三磷酸酶（ITPA）基因的多态性可能导致肌苷三磷酸焦磷酸酶的功能损害，在接受治疗的患者中，可增强持续病毒应答（SVR）并防止利巴韦林相关性贫血。本研究旨在探讨肌苷三磷酸酶基因多态性对SVR成绩的影响,治疗后患者血红蛋白下降和利巴韦林剂量减少。
方法：这项前瞻性队列研究是170名接受6个月索非布韦利巴韦林治疗的丙型肝炎感染患者。患者病毒载量,利巴韦林量的减少，肝功能检查,每月记录一次全血细胞计数。通过限制性片段长度多态性评估肌苷三磷酸酶变体rs1127354和rs7270101，并使用Sanger测序进行确认。多态性对利巴韦林累积减少的影响，和抗HCV治疗结果进行了研究。
结果：共有74.3%的患者有ITPArs1127354CC基因型，25.7%为CA和AA0%。ITPA基因型rs7270101-AA的频率为95%,AC5%,CC为0%。ITPArs1127354-CA对SVR成绩具有显著的积极影响，复发率为零。ITPArs1127354-CA基因型从基线到第1位显著(P<0.05)防止≥2g/dlHb降低,治疗的第2个月和第6个月。治疗期间,在rs1127354-CC基因型和rs7270101-AA基因型患者中经常观察到Hb降低≥10g/dl。与基因型CA相比，rs1127354-CC基因型的利巴韦林剂量减少显着（P<0.05）高，而rs7270101AA和非AA基因型的利巴韦林剂量减少没有显着差异。患者基线特征，如年龄，身体质量指数,rs1127354-CC基因型，和基线Hb与Hb显著降低显著相关。
结论：ITPA多态性的治疗前评估可以作为诊断工具，以发现有贫血风险的患者并提高治疗依从性。ITPA基因型rs1127354-CA有助于改善对利巴韦林剂量的依从性，并在服用基于利巴韦林的治疗时防止HCV患者的血红蛋白下降。然而,ITPArs1127354、rs7270101多态性对SVR成果无显著影响。
方法：这项前瞻性队列研究是170名接受6个月索非布韦利巴韦林治疗的丙型肝炎感染患者。患者病毒载量,利巴韦林量的减少，肝功能检查,每月记录一次全血细胞计数。通过限制性片段长度多态性评估肌苷三磷酸酶变体rs1127354和rs7270101，并使用Sanger测序进行确认。多态性对利巴韦林累积减少的影响，和抗HCV治疗结果进行了研究。
结果：共有74.3%的患者有ITPArs1127354CC基因型，25.7%为CA和AA0%。ITPA基因型rs7270101-AA的频率为95%,AC5%,CC为0%。ITPArs1127354-CA对SVR成绩具有显著的积极影响，复发率为零。ITPArs1127354-CA基因型从基线到第1位显著(P<0.05)防止≥2g/dlHb降低,治疗的第2个月和第6个月。治疗期间,在rs1127354-CC基因型和rs7270101-AA基因型患者中经常观察到Hb降低≥10g/dl。与基因型CA相比，rs1127354-CC基因型的利巴韦林剂量减少显着（P<0.05）高，而rs7270101AA和非AA基因型的利巴韦林剂量减少没有显着差异。患者基线特征，如年龄，身体质量指数,rs1127354-CC基因型，和基线Hb与Hb显著降低显著相关。
结论：ITPA多态性的治疗前评估可以作为诊断工具，以发现有贫血风险的患者并提高治疗依从性。ITPA基因型rs1127354-CA有助于改善对利巴韦林剂量的依从性，并在服用基于利巴韦林的治疗时防止HCV患者的血红蛋白下降。然而,ITPArs1127354、rs7270101多态性对SVR成果无显著影响。
