ITPA gene variation and ribavirin-induced anemia in patients with genotype 2 chronic hepatitis C treated with sofosbuvir plus ribavirin.
ITPA gene variation and ribavirin-induced anemia in patients with genotype 2 chronic hepatitis C treated with sofosbuvir plus ribavirin.
复制标题
使用索磷布韦加利巴韦林治疗的基因型 2 慢性丙型肝炎患者的 ITPA 基因变异和利巴韦林诱发的贫血。
DOI：
10.1111/hepr.12867
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发表时间：
2017
期刊：
影响因子：
4.2
通讯作者：
Watanabe M.
中科院分区：
文献类型：
--
作者：
Murakawa M;Asahina Y;Nagata H;Nakagawa M;Kakinuma S;Nitta S;Kawai-Kitahata F;Otani S;Kaneko S;Miyoshi M;Tsunoda T;Asano Y;Sato A;Itsui Y;Azuma S;Nouchi T;Furumoto Y;Asano T;Chuganji Y;Tohda S;Watanabe M.
AimSofosbuvir（SOF）和利巴韦林（RBV）联合治疗在许多基因型2型慢性丙型肝炎患者中产生持续反应。然而，RBV诱导的贫血是一种麻烦的副作用，可能会限制这种治疗。已知导致肌苷三磷酸酶（ITPA）缺乏的遗传变异可预防RBV诱导的溶血性贫血。本研究旨在评价SOF/RBV治疗的有效性和安全性与ITPA基因变异的关系。ITPA基因多态性和血红蛋白水平从基线下降，RBV剂量减少，持续病毒学应答（SVR）率之间的关系进行了analysed.ResultsOverall SVR在12周为94.4%（85/90）。在整个治疗过程中，ITPACA/AA基因型患者的贫血程度低于ITPACC基因型患者。ITPACA/AA变异的患者需要减少RBV剂量的百分比显著降低，当治疗前血红蛋白水平<12 g/dL时，差异更加明显。RBV剂量减少和血清白蛋白水平与SVR显著相关。结论ITPACA/AA基因型患者发生贫血的可能性低于ITPACC基因型患者，且更有可能完成SOF/RBV治疗。这些结果可能为预测药物诱导的不良事件提供有价值的药物遗传学诊断工具，特别是在既存贫血患者中。
AimSofosbuvir (SOF) and ribavirin (RBV) combination therapy produces a sustained response in many patients with genotype 2 chronic hepatitis C. However, RBV‐induced anemia is a troublesome side‐effect that may limit this treatment. Genetic variation leading to inosine triphosphatase (ITPA) deficiency is known to protect against RBV‐induced hemolytic anemia. This study aimed to evaluate the relationships between the efficacy and safety of SOF/RBV treatment andITPAgene variants.MethodsNinety patients with genotype 2 chronic hepatitis C treated with SOF/RBV were studied. The relationships among genetic polymorphisms ofITPAand the decline in hemoglobin levels from baseline, RBV dose reduction, and sustained virological response (SVR) rates were analyzed.ResultsOverall SVR at 12 weeks was 94.4% (85/90). Patients with theITPACA/AA genotypes had a lower degree of anemia throughout the therapy than those with theITPACC genotype. The percentage of patients requiring RBV dose reduction was significantly lower for those with theITPACA/AA variation, a difference even more apparent when the pretreatment hemoglobin level was <12 g/dL. The dose reduction of RBV and serum albumin level were significantly associated with SVR.ConclusionsPatients with theITPACA/AA genotype were less likely to develop anemia than those with theITPACC genotype and were more likely to complete SOF/RBV therapy. These results may provide a valuable pharmacogenetic diagnostic tool to predict drug‐induced adverse events, particularly in patients with pre‐existing anemia.