丙型肝炎病毒准种多样性与病毒血症水平、疾病活动度及干扰素疗效的关系

Relationship between diversity of hepatitis C virus quasispecies and viremia,activity of liver disease and response to interferon therapy

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 determine the relationship between diversity of hepatitis C virus quasispecies and viremia,activity of liver disease and response to interferon therapy.Methods HCV quasispecies heterogeneity in 68 patients with chronic hepatitis C were detected by single stranded conformational polymorphism (SSCP) analysis of the HCV E2 hypervaribale region 1 (HVR1);of these,48 were subsequently treated with interferon\|α for 6 months.Results HVR1 was amplified in 61 patients.The average number of SSCP bands was 6 2±2 4.Quasispecies heterogeneity significantly correlated with serum HCV RNA levels ( P<0 01 ),but not with serum ALT,AST levels and histological activity index ( P>0 05 ).Of the patients who received interferon therapy,43 were HVR1 positive.Patients who gained sustained response ( n=11 ) had lower pre\|treatement quasispecies heterogeneity(3 3±1 2) compared to those who had complete end\|of\|treatment response (ETR) with relapse (6 3±2 2, n=12,P<0 5 ) or no response (8 0±3 3, n=20,P<0 01 ).At the end of treatment,HVR1 could still be detected in 16 patients.The number of quasispecies heterogeneity in these patients decreased to 3 4±1 2,which was significantly lower than that in the patients who didn't receive interferon therapy (6 8±2 5, P<0 01 ).Of these 16 patients,10 had change in quasispecies patterns.Conclusion Increased quasispecies heterogeneity can cause high HCV viremia,but it is not related to severity of liver disease.Quasispecies heterogeneity is another marker to predict the response to interferon\|α in patients with chronic hepatitis C.