三磷酸次黄嘌呤核苷基因多态性对利巴韦林联合直接抗病毒药物治疗丙型肝炎致溶血性贫血的预测价值  

Association of inosine triphosphate pyrophosphatase gene polymorphisms with ribavirin combined with direct-acting antiviral agent in treatment of hepatitis C patients with hemolytic anemia

作　　者：徐金凤 仇丽霞[2] 于海滨[2] 刘义荣[2] 张晶[2] 柳雅立[2] 林伟[2] XU Jinfeng;QIU Lixia;YU Haibin;LIU Yirong;ZHANG Jing;LIU Yali;LIN Wei(Department of Infectious Diseases,Hebei Petrochina Central Hospital,Langfang,Hebei 065000,China;Department of Hepatitis C&Toxic Liver Diseases,Beijing YouAn Hospital,Capital Medical University,Beijing 100071,China)

机构地区：[1]河北中石油中心医院感染科,河北廊坊065000 [2]首都医科大学附属北京佑安医院丙肝与中毒性肝病科,北京100071

出　　处：《临床肝胆病杂志》2021年第10期2320-2323,共4页Journal of Clinical Hepatology

基　　金：北京市属医院科研培育计划项目(PX2018058);首都医学大学附属北京佑安医院院内中青年人才孵育项目(YNKTTS20180114);廊坊市科技支撑计划项目(2019013010)。

摘　　要：目的探讨慢性丙型肝炎治疗过程中利巴韦林(RBV)引起溶血性贫血的影响因素,为临床早期预测利巴韦林相关溶血性贫血发生提供借鉴。方法选取2018年1月—2019年7月于河北中石油中心医院门诊及住院就诊的丙型肝炎且应用直接抗病毒药物(DAA)联合RBV方案抗病毒治疗患者。三磷酸次黄嘌呤肌苷(ITPA)基因rs1127354位点主要等位基因是C等位基因,次要等位基因为A等位基因,将AA与AC合并与CC基因型进行比较。在治疗过程中,当Hb水平<100 g/L时,RBV减量至600 mg;当Hb<85 g/L时停用RBV治疗。在抗病毒治疗前进行血常规、肝功能、肝脏硬度值、HCV RNA、HCV病毒基因型及ITPA基因型检测,在2、4、8、12周对患者进行血常规检测。不符合正态分布的计量资料组间比较采用Mann-Whitney U检验。结果本研究共纳入病例49例,慢性丙型肝炎患者22例,肝硬化27例,持续病毒学应答率为95.9%。因贫血RBV减量者3例(其中AA/AC组2例,CC组1例),停药3例(其中AA/AC组1例,CC组2例),均为肝硬化患者,6例患者最终均达到持续病毒学应答。DAA+RBV抗HCV治疗过程中,RBV相关溶血的发生较轻微,AA/AC型与CC型两组患者Hb较基线下降最大值比较差异无明显统计学意义(Z=-0.18,P=0.87)。结论本研究在RBV联合DAA治疗过程中,因为贫血RBV停药和减量的均为肝硬化患者,ITPA基因型与患者Hb较基线下降最大值无明显统计学关系,故在应用RBV前进行ITPA基线检测未能增加治疗过程中的安全性,因此不建议进行常规的ITPA基因多态性检测。Objective To investigate the influencing factors for ribavirin(RBV)-induced hemolytic anemia in the treatment of chronic hepatitis C,and to provide a reference for the early prediction of ribavirin-related hemolytic anemia in clinical practice.Methods A total of 49 patients with chronic hepatitis C who attended or were hospitalized in Hebei Petrochina Central Hospital from January 2018 to July 2019 and received antiviral therapy with direct-acting antiviral agent(DAA)and RBV were enrolled,with a major allele of C allele and a minor allele of A allele at the rs1127354 locus of the inosine triphosphate pyrophosphatase(ITPA)gene,and the patients with AA and AC genotypes were compared with those with CC genotype.During treatment,RBV was reduced to 600 mg when hemoglobin(Hb)level was<100 g/L and was withdrawn when Hb level was<85 g/L.Routine blood test,liver function,liver stiffness measurement,HCV RNA,HCV genotype,and ITPA genotype were measured before antiviral therapy,and the routine blood test was performed at weeks 2,4,8,and 12 of treatment.The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups.Results A total of 49 patients were enrolled in this study,among whom 22 had chronic hepatitis C and 27 had liver cirrhosis,with a sustained virologic response(SVR)rate of 95.9%.The dose of RBV was reduced in 3 patients(2 in the AA/AC group and 1 in the CC group)due to anemia,and RBV was withdrawn in 3 patients(1 in the AA/AC group and 2 in the CC group);all these 6 patients had liver cirrhosis and finally achieved SVR.During the anti-HCV therapy with DAA+RBV,there was relatively mild RBV-related hemolysis,and the maximum reduction in Hb from baseline was compared between the patients with AA/AC genotype at ITPA rs1127354 and those with CC genotype,which showed no significant difference between the two groups(Z=-0.18,P=0.87).Conclusion During the treatment with RBV+DAA,RBV is withdrawn or reduced for liver cirrhosis patients due to anemia,and no obvious statistical relati

关 键 词：丙型肝炎 慢性 贫血 溶血性 利巴韦林 危险因素 

分 类 号：R512.63[医药卫生—内科学]