乙肝病毒前S基因變異與晚期乙肝肝病關(guān)聯(lián)性的臨床研究
發(fā)布時(shí)間:2018-05-04 08:56
本文選題:乙型肝炎病毒 + 前S基因; 參考:《昆明醫(yī)科大學(xué)》2014年碩士論文
【摘要】:[目的]研究昆明地區(qū)3家三級(jí)甲等醫(yī)院就診的乙肝病毒感染患者病毒前S基因變異與晚期乙肝肝病的臨床關(guān)聯(lián)性。 [方法]收集21例慢性乙型肝炎(CHB)患者(包括發(fā)生慢加急性肝衰竭(ACLF)患者5例)、41例乙肝相關(guān)性肝硬化(LC)患者(包括發(fā)生ACLF患者5例)及9例乙肝相關(guān)性肝細(xì)胞癌(HCC)患者的血樣標(biāo)本及臨床資料,提取所有血清病毒HBV DNA,使用乙型肝炎病毒基因分型檢測(cè)試劑盒進(jìn)行HBV基因型分型,PCR擴(kuò)增HBV DNA前S基因,所得陽(yáng)性PCR產(chǎn)物進(jìn)行測(cè)序,采用Chromas軟件分析測(cè)序圖,DNAstar軟件分析測(cè)序結(jié)果,使用SPSS軟件進(jìn)行統(tǒng)計(jì)分析,了解乙肝病毒前S區(qū)變異與晚期乙肝肝病的臨床關(guān)聯(lián)性。 [結(jié)果] 一、測(cè)序結(jié)果 1、本實(shí)驗(yàn)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組分別為14vs7、28vs12、7vs2,三組中基因型C所占比率差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。PreS區(qū)變異檢出率為46.48%(33/71),其中PreS2變異19例,PreS1+PreS2變異12例,PreS1變異2例。PreS變異率在CHB(不包括ACLF)、LC、HCC三組中分別為18.75%、48.78%、66.67%,CHB組PreS區(qū)變異率低于LC組(P0.05)和HCC組(P0.05),而LC與HCC組間差異不明顯(P0.05);并且,ACLF組PreS區(qū)變異率(80%)明顯高于CHB組(18.75%)(P0.005)。 2、PreS區(qū)變異發(fā)生組與未發(fā)生組的HBV DNA≥104copies/ml比率分別為30(99.9%),19(50.0%),兩組間HBV DNA≥104copies/ml比率差異顯著(P0.001),但是,兩組間性別、年齡差異及基因型C所占比率相比較差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 二、入組患者臨床資料 1、CHB(不包括ACLF,16例)、LC(41例)和HCC(9例)三組間性別、年齡差異、HBeAg陽(yáng)性分布及HBV DNA≥104copies/ml比率相比較差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 2、在HBV相關(guān)性ACLF組(10例)與CHB組(不包括ACLF,16例)間,性別、年齡差異、HBeAg (?)日性分布及HBV DNA≥104copies/ml比率相比較差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 3、比較CHB、LC和HCC組的肝功能(ALT、ALB、TBIL),三組間ALB差異有統(tǒng)計(jì)學(xué)意義(P0.001),CHB組較LC組、HCC組高(P0.001),但LC組與HCC組無(wú)明顯差異(P0.05);CHB組TBIL較LC組(P0.05)、HCC組低(P0.05),LC組較HCC組低(P0.05),TBIL隨著病情加重而升高。ALT在三組中變異度均比較大,在三組間進(jìn)行比較無(wú)意義。 4、入組71例患者中,抗病毒治療率為43.66%(3I/71),在CHB組(不包括ACLF)、LC組、HCC組分別為62.5%、41.46%、22.22%,三組間差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。與CHB組(不包括ACLF)相比,HBV相關(guān)性ACLF組抗病毒治療率(40%)差異亦無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 [結(jié)論] 1、昆明地區(qū)3家三級(jí)甲等醫(yī)院就診HBV感染者基因型以B型和C型為主,其中基因型C是優(yōu)勢(shì)基因型。 2、PreS區(qū)變異以PreS2變異最常見(jiàn),PreS1變異最少。 3、PreS區(qū)變異可引起高水平病毒復(fù)制;在晚期乙肝肝病中,隨著病情的進(jìn)展,PreS區(qū)變異檢出率逐漸增高;且PreS區(qū)變異者可能更易發(fā)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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