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目的 了解丙型肝炎病毒 (HCV)准种变异与病毒血症水平、疾病活动度及干扰素疗效的关系。方法 采用针对HCVE2高变区 1 (HVR1 )的单链构象多态性分析法 (SSCP)对 68例慢性丙型肝炎患者进行HCV准种检测 ,分析准种数目与HCVRNA、ALT、AST水平及肝组织活动指数 (HAI)的相关性。对其中 48例给予干扰素治疗 ,分析准种数目对干扰素应答效果的影响。结果 61例HVR1SSCP阳性 ,HCV准种数目为 (6 2± 2 4)条。准种数量与HCVRNA水平显著相关 (P <0 0 1 ) ,与ALT、AST及HAI无明显相关 (P >0 0 5)。干扰素治疗患者中 ,43例HVR1阳性 ,持续应答者治疗前HCV准种数量 (3 3± 1 2 ,n =1 1 )显著少于获得治疗终点应答 (ETR)伴复发者 (6 3± 2 2 ,n =1 2 ,P <0 0 5)或无应答者 (8 0± 3 3 ,n=2 0 ,P <0 0 1 )。治疗结束时 ,干扰素组仍有 1 6例检测出HCV准种 ,但准种条数降为 (3 4± 1 2 )条 ,与未接受干扰素治疗病例的准种数目 (6 8± 2 5)相比差异有显著性 ,P <0 0 1 ) ,且其中 1 0例准种模式发生了改变。结论 HCV准种多样性可引起较高的病毒血症水平 ,但与疾病活动度无关 ;准种数目可作为预测慢性丙型肝炎干扰素疗效的指标。
Objective To understand the relationship between hepatitis C virus (HCV) quasispecies variation and viremia, disease activity and efficacy of interferon. Methods Single-strand conformation polymorphism (SSCP) analysis of HCVE2 hypervariable region 1 (HVR1) was performed in 68 patients with chronic hepatitis C. The number of quasispecies was compared with that of HCV RNA, ALT, AST and liver Organizational Activity Index (HAI) relevance. Interferon treatment was given to 48 of them, and the effect of quasispecies number on interferon response was analyzed. Results 61 cases of HVR1SSCP positive, HCV quasispecies number (6 2 ± 2 4). The number of quasispecies was significantly associated with HCV RNA level (P <0.01), but not with ALT, AST and HAI (P> 0.05). Of 43 patients with HVR1 who were treated with interferon, the number of HCV quasispecies (3 3 ± 1 2, n = 1 1) before treatment was significantly lower in patients with persistent responders than those with relapse (6 3 ± 2) 2, n = 12, P <0 05) or no responders (80 ± 3 3, n = 20, P <0.01). At the end of treatment, HCV quasispecies was still detected in 16 of the interferon groups but the number of quasi-species seeds was reduced to (34 ± 1 2) and the number of quasispecies (68 ± 2) cases without interferon treatment 5), P <0.01), and of the 10 quasi-species patterns changed. Conclusion The diversity of HCV quasispecies can induce higher levels of viremia, but has no relation with disease activity. The quasispecies can be used as an index to predict the efficacy of interferon in chronic hepatitis C virus.