ITPA genetic variants influence efficacy of PEG-IFN/RBV therapy in older patients infected with HCV genotype 1 and favourable IL28B type.
ITPA genetic variants influence efficacy of PEG-IFN/RBV therapy in older patients infected with HCV genotype 1 and favourable IL28B type.
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ITPA 基因变异影响 PEG-IFN/RBV 治疗感染 HCV 基因型 1 和有利 IL28B 型的老年患者的疗效。
DOI：
10.1111/jvh.12171
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Mizokami M.
中科院分区：
文献类型：
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作者：
Matsuura K;Tanaka Y;Watanabe T;Fujiwara K;Orito E;Kurosaki M;Izumi N;Sakamoto N;Enomoto N;Yatsuhashi H;Kusakabe A;Shinkai N;Nojiri S;Joh T;Mizokami M.
在聚乙二醇化干扰素（PEG - IFN）加RBV治疗期间，肌苷三磷酸酶（ITPA）基因变异与利巴韦林（RBV）诱导的贫血密切相关。然而，itpag2基因变异的治疗效果尚未得到充分的探讨。我们招募了309名基因型1型丙型肝炎病毒感染者，他们接受PEG - IFN加RBV治疗48周。对itpasnp: rs1127354和il28bsnp: rs8099917进行基因分型。我们检查了治疗开始后12周严重贫血的危险因素和治疗效果。严重贫血（血红蛋白（Hb）降低≥3 g/dL或<10 g/dL）的发生率在CC患者中（rs1127354）[65%(145/224), 33%(73/224)]高于CA/AA患者[25% (21/85),6% (8/85)]（P<0.0001）。亚型、预处理Hb水平和年龄是严重贫血的独立预测因素：Hb < 10 g/dL。在il28b有利型中，≥60岁CA/AA患者的持续病毒学应答率高于CC患者[71% (22/31)vs40% (26/65)，P=0.005]，尽管在<60岁患者中，根据itg基因变异的治疗效果没有显着差异。CA/AA患者给予RBV≥80%剂量的患者比例显著高于CC患者（P=0.025），复发率较低。总之，itg基因变异与严重RBV诱导的贫血相关，并可能影响PEG - IFN加RBV治疗老年il28b有利型患者的疗效。
Inosine triphosphatase (ITPA) genetic variants are strongly associated with ribavirin (RBV)‐induced anaemia during pegylated interferon (PEG‐IFN) plus RBV therapy. However, the treatment efficacy ofITPAgenetic variants has not been fully explored. We enrolled 309 individuals infected with hepatitis C virus genotype 1, who were treated with PEG‐IFN plus RBV for 48 weeks. TheITPASNP: rs1127354 andIL28BSNP: rs8099917 were genotyped. We examined the risk factors for severe anaemia up to week 12 after the start of treatment and treatment efficacy. The incidence of severe anaemia, ≥3 g/dL reduction or <10 g/dL of haemoglobin (Hb) up to week 12, was more frequent in patients with CC at rs1127354 [65% (145/224), 33% (73/224)] than in those with CA/AA [25% (21/85), 6% (8/85)] (P<0.0001).ITPAgenotype, pretreatment Hb level and age were independent predictive factors for severe anaemia: Hb < 10 g/dL. InIL28Bfavourable type, the sustained virologic response rate was higher in ≥60‐year‐old patients with CA/AA than in those with CC [71% (22/31)vs40% (26/65),P=0.005], although there was no significant difference in treatment efficacy according toITPAgenetic variants in the <60‐year‐old patients. The proportion of patients administered ≥80% of the dosage of RBV was significantly higher in the patients with CA/AA than in those with CC (P=0.025), resulting in a lower relapse rate. In conclusion,ITPAgenetic variants were associated with severe RBV‐induced anaemia and could influence the efficacy of PEG‐IFN plus RBV treatment among elderly patients withIL28Bfavourable type.