中文摘要：

目的比较慢性重型乙型肝炎（CSHB）与慢性乙型肝炎（CHB）患者HBV前S/S蛋白特异性细胞毒性T细胞（CTL）表位变异的差异,探讨乙型肝炎重症化和慢性化的机制。方法对262例乙型肝炎患者的血清样本进行HLA-A2分型;用巢式PCR扩增血清HBV前S/S基因并对PCR产物进行序列测定;根据HBV前S/S基因序列,用VirusBlast软件鉴定患者感染的HBV基因型;用VectorNTI软件对目前已知的13个HLA-A2限制性前S/S蛋白特异性CTL表位进行序列分析。结果123例（46.9%）患者HLA-A2阳性,其中CSHB71例,CHB52例。CTL表位变异分析结果如下：（1）两组间所有患者进行比较,患者S177-185和S338-347表位变异发生率有显著差异（P〈0.05）;（2）两组间HBVB基因型患者进行比较,患者S131-139、S183-191和S204-212表位变异发生率有极显著差异（P〈0.01）;（3）两组间HBVC基因型患者进行比较,CSHB组患者的S131-139表位较CHB组患者有增高（P=0.05）。结论某些HBV前S/S蛋白特异性CTL表位在CSHB与CHB患者间变异有明显差异,受病毒基因型影响,CTL表位变异可能与乙型肝炎的重症化和慢性化机制相关。

英文摘要：

Objective For the purpose of exploring the possible mechanisms of severity and chronieity of hepatitis B, the difference in mutation of HBV pre S/S protein-specific CTL epitopes is compared between the patients with chronic severe hepatitis B （CSHB） and chronic hepatitis B （CHB）. Methods HLA-A2 typing was performed among 262 patients with hepatitis B. Nested PCR was used to amplify HBV pre S/S gene followed by sequencing of PCR products. HBV genotyping was determined based on the pre S/S gene sequence by VirusBlast software. The mutations of 13 HLA-A2-restricted pre S/S protein-specific CTL epitopes were analyzed by Vector NTI software. Results Out of 123 patients （46. 9%） identified as HLA-A2 positive, 71 were the patients with CSHB and 52 were with CHB. The results of CTL epitope mutation were as follows. （1） When all patients of CSHB and CHB groups were examined, there was significant difference （P〈0. 05） in the mutation occurrence of S177-185 and S338-347 epitopes. （2） When only HBV genotype B patients were examined, there was very significant difference （P〈0. 01） in the mutation occurrence of S131-139, S183-191 and S204-212 epitopes between the two groups. （3） When only HBV genotype C patients were examined, the mutation occurrence of S131-139 was obviously higher （P=0. 05） in CSHB group than in CHB group. Conclusions Obvious difference exists in the mutation occurrence of a few HBV pre S/S protein epitopes which is affected by HBV genotype. The mutation factor is possibly associated with the pathogenesis of severity and chronicity and thus needs to be further studied.