PR方案治疗慢性丙型肝炎患者ITPA基因rs1127354位点多态性与利巴韦林相关性溶血关系探讨

Impact of ITPA gene rs1127354 polymorphism on ribavirin-related hemolysis in patients with chronic hepatitis C receiving PR therapy

目的探讨应用标准抗病毒(PR)方案治疗慢性丙型肝炎(CHC)患者三磷酸次黄嘌呤核苷(ITPA)基因多态性对抗病毒疗效及其对利巴韦林(RBV)相关性溶血的影响。方法2016年3月~2018年3月我院收治的CHC患者235例,给予聚乙二醇化干扰素α-2a联合RBV治疗24~48 w。采用基因测序法检测血ITPA基因rs1127354位点多态性。结果经检测,发现ITPA基因型rs1127354位点为CC型193例和AA/AC型42例;在完成24周疗程的188例(CC型152例和AA/AC型36例)CHC患者中,AA/AC型患者快速病毒学应答和早期病毒学应答率分别为44.4%和47.2%,与CC型的42.1%和42.7%比,无显著性差异(P>0.05),而持续病毒学应答率为72.2%,显著高于CC型的53.3%(P<0.05);在治疗4周、8周、12周和24周,AA/AC型患者Hb水平分别为(138.2±14.7)g/L、(130.5±12.6)g/L、(123.7±12.5)g/L和(118.0±10.2)g/L,显著高于CC型【分别为(132.3±13.9)g/L、(113.1±10.5)g/L、(108.4±9.4)g/L和(106.7±11.3)g/L,P<0.05】。结论在PR方案治疗的慢性丙型肝炎患者,ITPA基因(rs1127354)CC基因型较AA/AC基因型更易发生RBV相关性溶血,而ITPA基因型与抗病毒效果密切相关,临床应加以重视和预防性处理。

Objective The aim of this study was to explore the impact of inosine triphosphatase genotype(ITPA)gene rs1127354 polymorphism on ribavirin(RBV)-related hemolysis in patients with chronic hepatitis C(CHC)receiving pegylated interferon alpha-2a and RBV(PR)therapy.Methods 235 patients with CHC were recruited in our hospital between March 2016 and March 2018,and all patients received PR therapy for 24 to 48 weeks.The blood ITPA gene locus rs1127354 were detected by gene sequencing.Results The gene sequencing showed that ITPA genotype rs1127354 locus were CC in 93 and AA/AC in 42;188 patients with CHC(152 with CC and 36 with AA/AC)completed the 24-week antiviral regimen,and the rapid virological response(RVR)and early virological response(EVR)in patients with genotype AA/AC were 44.4%and 47.2%,not significantly different as compared to 42.1%and 42.7%in those with genotype CC(P>0.05),while the sustained virological response(SVR)was 72.2%,significantly higher than 53.3%(P<0.05)in patients with genotype CC;at the end of week 4,8,12 and 24,blood hemoglobin levels in patients with genotype AA/AC were(138.2±14.7)g/L,(130.5±12.6)g/L,(123.7±12.5)g/L and(118.0±10.2)g/L,significantly higher than【(132.3±13.9)g/L,(113.1±10.5)g/L,(108.4±9.4)g/L and(106.7±11.3)g/L,respectively,P<0.05】in patients with genotype CC.Conclusion The CHC patients with ITPA genotype CC are more prone to RBV-related hemolysis during PR antiviral therapy,which should be taken into consideration in clinical decision-making process.