乙肝病毒前S基因变异与晚期乙肝肝病关联性的临床研究

发布时间：2018-05-04 08:56

  本文选题：乙型肝炎病毒 + 前S基因　； 参考：《昆明医科大学》2014年硕士论文

【摘要】：[目的]研究昆明地区3家三级甲等医院就诊的乙肝病毒感染患者病毒前S基因变异与晚期乙肝肝病的临床关联性。 [方法]收集21例慢性乙型肝炎(CHB)患者(包括发生慢加急性肝衰竭(ACLF)患者5例)、41例乙肝相关性肝硬化(LC)患者(包括发生ACLF患者5例)及9例乙肝相关性肝细胞癌(HCC)患者的血样标本及临床资料,提取所有血清病毒HBV DNA,使用乙型肝炎病毒基因分型检测试剂盒进行HBV基因型分型,PCR扩增HBV DNA前S基因,所得阳性PCR产物进行测序,采用Chromas软件分析测序图,DNAstar软件分析测序结果,使用SPSS软件进行统计分析,了解乙肝病毒前S区变异与晚期乙肝肝病的临床关联性。 [结果] 一、测序结果 1、本实验71例中基因型C49例,基因型B21例,混合基因型B+C1例。基因型C和B在CHB、LC、HCC组分别为14vs7、28vs12、7vs2,三组中基因型C所占比率差异无统计学意义(P0.05)。PreS区变异检出率为46.48%(33/71),其中PreS2变异19例,PreS1+PreS2变异12例,PreS1变异2例。PreS变异率在CHB(不包括ACLF)、LC、HCC三组中分别为18.75%、48.78%、66.67%,CHB组PreS区变异率低于LC组(P0.05)和HCC组(P0.05),而LC与HCC组间差异不明显(P0.05)；并且,ACLF组PreS区变异率(80%)明显高于CHB组(18.75%)(P0.005)。 2、PreS区变异发生组与未发生组的HBV DNA≥104copies/ml比率分别为30(99.9%),19(50.0%),两组间HBV DNA≥104copies/ml比率差异显著(P0.001),但是,两组间性别、年龄差异及基因型C所占比率相比较差异均无统计学意义(P0.05)。 二、入组患者临床资料 1、CHB(不包括ACLF,16例)、LC(41例)和HCC(9例)三组间性别、年龄差异、HBeAg阳性分布及HBV DNA≥104copies/ml比率相比较差异均无统计学意义(P0.05)。 2、在HBV相关性ACLF组(10例)与CHB组(不包括ACLF,16例)间,性别、年龄差异、HBeAg (?)日性分布及HBV DNA≥104copies/ml比率相比较差异均无统计学意义(P0.05)。 3、比较CHB、LC和HCC组的肝功能(ALT、ALB、TBIL),三组间ALB差异有统计学意义(P0.001),CHB组较LC组、HCC组高(P0.001),但LC组与HCC组无明显差异(P0.05)；CHB组TBIL较LC组(P0.05)、HCC组低(P0.05),LC组较HCC组低(P0.05),TBIL随着病情加重而升高。ALT在三组中变异度均比较大,在三组间进行比较无意义。 4、入组71例患者中,抗病毒治疗率为43.66%(3I/71),在CHB组(不包括ACLF)、LC组、HCC组分别为62.5%、41.46%、22.22%,三组间差异无统计学意义(P0.05)。与CHB组(不包括ACLF)相比,HBV相关性ACLF组抗病毒治疗率(40%)差异亦无统计学意义(P0.05)。 [结论] 1、昆明地区3家三级甲等医院就诊HBV感染者基因型以B型和C型为主,其中基因型C是优势基因型。 2、PreS区变异以PreS2变异最常见,PreS1变异最少。 3、PreS区变异可引起高水平病毒复制；在晚期乙肝肝病中,随着病情的进展,PreS区变异检出率逐渐增高；且PreS区变异者可能更易发生ACLF。
[Abstract]:[objective] to study the clinical relationship between HBV pres gene mutation and advanced hepatitis B liver disease in 3 hospitals of Grade 3A in Kunming. [methods] 21 patients with chronic hepatitis B (including 5 patients with chronic and acute hepatic failure) (including 5 patients with ACLF) and 9 patients with Hepatitis B associated hepatocellular carcinoma (HCC) were collected. Blood samples and clinical data of patients with HCC, HBV DNA of all serum viruses was extracted, and HBV genotyping kit was used to amplify HBV DNA pre-S gene. The positive PCR products were sequenced. The sequencing results were analyzed by Chromas software and DNAstar software. SPSS software was used to analyze the clinical relationship between HBV preS region variation and advanced hepatitis B liver disease. [results] I. Sequencing results. 1. There were 71 cases of genotype C 49, genotype B 21 and mixed genotype B C1. Genotype C and B were 14vs728vs127vs2.There was no significant difference in the ratio of genotype C among the three groups. The positive rate of variation of genotype C was 46.48% 33 / 71G, of which 19 cases of PreS2 mutation were preS1 PreS2 variation 12 cases were PreS1 variation. The variation rate of PreS region in group B was lower than that in group LC (P 0.05) and group HCC (P 0.05), but there was no significant difference between group LC and group HCC (P 0.05), and the variation rate of PreS in group B was significantly higher than that in group CHB (P 0.005). 2the ratio of HBV DNA 鈮，

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