CAJ | 학술논문

目的探讨HCV-1b型ISDR区、PKR-BD区、NS5A-V3功能区及E2-PePHD功能区的基因序列突变程度与干扰素/利巴韦林联合治疗慢性丙型肝炎疗效的相关性。方法收集拟进行干扰素和利巴韦林联合治疗的慢性丙型肝炎患者的血清标本以及实验室数据和随后的临床治疗资料。提取血清标本RNA，RT-PCR鉴定HCV基因型。选取HCV-1b型阳性的标本，利用RT-PCR分别扩增ISDR区、PKR-BD区、NS5A-V3功能区及E2-PePHD功能区的基因片段，对PCR产物进行基因测序，与标准株的基因序列比对，确定各区的氨基酸突变位点和数量。回顾性分析各基因区氨基酸突变数量与干扰素/利巴韦林疗效的相关性。结果169例慢性丙型肝炎患者中HCV-1b型患者124例，占74.4%；在干扰素/利巴韦林联合治疗满12个月并随访满6个月的HCV-1b型感染者中，治疗前NS5A区的ISDR突变程度与持续病毒反应（SVR）的发生率之间呈显著相关性（P＜0.05）。突变型（突变氨基酸数≥4）患者群的SVR发生率为85.7%，中间型（突变氨基酸数为1～3）患者群的SVR发生率为55%，而野生型患者群的SVR发生率最低，仅为30%；而PKR-BD区、NS5A-V3功能区以及E2-PePHD功能区的氨基酸突变数量与SVR发生率无显著相关性（P＞0.05）。结论 HCV-1b型感染者治疗前NS5A区的ISDR突变程度对于干扰素/利巴韦林联合治疗的疗效具有很大的预测价值。
목적탐토HCV-1b형ISDR구、PKR-BD구、NS5A-V3공능구급E2-PePHD공능구적기인서렬돌변정도여간우소/리파위림연합치료만성병형간염료효적상관성。방법수집의진행간우소화리파위림연합치료적만성병형간염환자적혈청표본이급실험실수거화수후적림상치료자료。제취혈청표본RNA，RT-PCR감정HCV기인형。선취HCV-1b형양성적표본，이용RT-PCR분별확증ISDR구、PKR-BD구、NS5A-V3공능구급E2-PePHD공능구적기인편단，대PCR산물진행기인측서，여표준주적기인서렬비대，학정각구적안기산돌변위점화수량。회고성분석각기인구안기산돌변수량여간우소/리파위림료효적상관성。결과169례만성병형간염환자중HCV-1b형환자124례，점74.4%；재간우소/리파위림연합치료만12개월병수방만6개월적HCV-1b형감염자중，치료전NS5A구적ISDR돌변정도여지속병독반응（SVR）적발생솔지간정현저상관성（P＜0.05）。돌변형（돌변안기산수≥4）환자군적SVR발생솔위85.7%，중간형（돌변안기산수위1～3）환자군적SVR발생솔위55%，이야생형환자군적SVR발생솔최저，부위30%；이PKR-BD구、NS5A-V3공능구이급E2-PePHD공능구적안기산돌변수량여SVR발생솔무현저상관성（P＞0.05）。결론 HCV-1b형감염자치료전NS5A구적ISDR돌변정도대우간우소/리파위림연합치료적료효구유흔대적예측개치。
Objective To investigate whether mutations in ISDR, PKR-BD, NS5A-V3 and E2-PePHD regions of HCV-1b genotype inlfuence the efifcacy of interferon/ribavirin in patients with chronic HCV-1b infection. Methods The pretreatment serum samples from patients, who had chronic infection of HCV-1b and completed the course of interferon/ribavirin combination therapy as well as a 6-months follow-up, were collected, respectively. The pretreatment mutations in nucleic acid sequence of ISDR, PKR-BD, NS5A-V3 and E2-PePHD regions of HCV-1b were identified by RT-PCR products sequencing followed by comparison with the prototype sequence (HCV-J). Correlationship with the clinical efifcacy of interferon/ribavirin combination therapy was then analyzed, retrospectively. Results Total of 169 patients with chronic HCV infection were enrolled in the retrospective study. Among these patients, 124 (74.4%) were infected by HCV-1b genotype. The statistical analysis indicated a significant correlationship between the mutations in ISDR and sustained virological response (SVR) to interferon/ribavirin treatment (P<0.05). The SVR rates of patients infected with wild-type, intermediate-type and mutant-type ISDR strains were 30%, 55%and 85.7%, respectively. However, there was no signiifcant association among the mutations in PKR-BD, NS5A-V3 and E2-PePHD regions and SVR (P>0.05). Conclusions The pretreatment mutations in ISDR of NS5A gene have important predictive value for therapeutic effects of interferon/ribavirin to patients with HCV-1b infection.