目的:接受利巴韦林(RBV)治疗的HCV感染患者中肌苷三磷酸酶(ITPA)rs1127354多态性之间的关联,药物不良反应的风险和转归尚不清楚.进行了荟萃分析,以系统地总结和阐明这种关联。
方法:在PubMed中进行了全面搜索,Embase和WebofSciences,并从文献检索中选择了22项研究。通过固定或随机效应模型估计集合比值比(OR)和95%置信区间(95%CI)。
结果:评估了四个结果:(a)血红蛋白下降:rs1127354CCVSCAAA与血红蛋白下降显着相关(OR=10.59,95%CI=6.39-17.54);(b)重度贫血:rs1127354CCVSCAAA(OR=16.24%CI=治疗期间,治疗期间的剂量减少0.65%,尽管差异为0.21%,但与重度敏感性分析提示这一结果并不稳健.
结论:ITPArs1127354CC多态性患者更容易发生溶血性贫血,严重贫血和SVR降低。测试这种遗传多态性可能会使患者受益。
OBJECTIVE: The association between inosine triphosphatase (ITPA) rs1127354 polymorphisms in HCV-infected patients receiving ribavirin (RBV)-based therapy, and the risk of adverse drug reaction and outcomes is still unclear. A meta-analysis was conducted to summarize and clarify this association systematically.
METHODS: A comprehensive search was performed in PubMed, Embase and Web of Sciences, and twenty-two studies were selected from the literature search. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were estimated by either fixed- or random-effects models.
RESULTS: Four outcomes were evaluated: (a) haemoglobin decline: significant associations with haemoglobin decline were found for rs1127354 CC VS CA + AA (OR = 10.59, 95% CI = 6.39-17.54); (b) severe anaemia: significant association with severe anaemia was observed for rs1127354 CC VS CA + AA (OR = 16.24, 95% CI = 6.21-42.43); (c) sustained virological response (SVR): CC genotype carriers had a decrease SVR during treatment (OR = 0.65, 95% CI = 0.52-0.81); (d) RBV dose reduction or stopping treatment: although statistical evidence of an association was found between the polymorphism and RBV dose reduction during treatment (OR = 1.80, 95% CI = 1.03-3.13), the sensitivity analysis suggested this result was not robust.
CONCLUSIONS: Patients with ITPA rs1127354 CC polymorphism are more likely to develop haemolytic anaemia, severe anaemia and decreased SVR. Testing for this genetic polymorphism may benefit patients.