Study on the relationship between X region mutations of chronic hepatitis B and curative effect of pegylated interferon α-2a

目的 探讨慢性乙型肝炎治疗前X区变异与聚乙二醇干扰素α-2a治疗疗效的相关性.方法 收集HBeAg阳性慢乙肝患者,给予聚乙二醇干扰素α-2a治疗,收集基线及治疗12周后的患者血清.12周后根据HBVDNA下降水平分为三组:DNA应答组、DNA部分应答组、DNA无应答组.对患者基线血清进行全序列扩增、克隆、测序.通过logistic回归分析确定与聚乙二醇干扰素α-2a治疗疗效相关的变异位点,取P＜0.05为有统计学意义.结果 共对29例患者进行了数据分析,DNA应答组7人、DNA部分应答组9人、DNA无应答组13人.各组间基线ALT水平比较(X2 =10.732,P=0.005),差异有统计学意义.年龄、性别、HBVDNA、HBsAg、HBeAg、HBeAb比较,差异均无统计学意义.共获得306条序列,进行统计学分析及结合临床应答,得到X区核苷酸变异位点共16个,进一步进行多因素logistic回归分析发现ntG1386A、ntG1437A、ntGl515A有利于干扰素抗病毒治疗;ntC1383A、ntT1425C、ntG1512A不利于干扰素抗病毒治疗.氨基酸水平分析发现V5M、G22S和D48N是干扰素治疗的有利因素,V30L和A47T是不利因素.结论 基线X区变异与聚乙二醇干扰素α-2a治疗疗效可能相关.Objective To study the relationship between X region mutations of chronic hepatitis B and curative effect of pegylated interferon α-2a.Methods Patients with chronic hepatitis B (e antigen positive) were enrolled,treated with pegylated interferon α-2a.Enrolled patients serum specimens of base line and after 12 weeks treatment were collected.After 12 weeks,depending on the HBV DNA falling degree,patients were divided into three groups:DNA response group,DNA partial response group,DNA non-response group.Then HBV full genome in the serum (baseline) was amplificated,cloned and sequenced.Analysis the relationship of X region mutations and pegylated interferon α-2a treatment-related effect by logistic regression.P ＜ 0.05 was considered statistically significant.Results 29 patients data was analyzed,which including T patients from DNA response group,9 palients from DNA partial response group and 13 palients from DNA non-response group.At baseline,the difference of ALT was statistically significant(x2 =10.732,P =0.005).Among three groups,the differences of age,gender,HBVDNA,HBsAg and HBeAg,HBeAb were not statistically significant.Total of 306 sequences were obtained.The number of X region nucleotide mutation sites,according to statistically significant and clinical response,was 16.Multivariate logistic regression analysis showed ntG1386A,ntG1437A and ntG1515A were in favor of interferon antiviral therapy;but ntC1383 A,ntT1425 C and ntG1512A are risk factors unfavorable for interferon antiviral therapy.Amino acid level analysis found that V5M,G22S and D48N were favorable factors for interferon treatment,but V30L and A47T were negative factors for interferon treatment.Conclusions X region mutations may be correlated with therapeutic effect of pegylated interferon α-2a.国家自然科学基金; 北京市科学技术委员会重大项目(D121100003912001) National Natural Science Fundation of China; Beijing Science and Technology Commission Major Project中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)4389-3923