發(fā)布時(shí)間：2018-06-01 09:39

  本文選題：乙型肝炎病毒 + HBV-DNA　； 參考：《寧夏醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的調(diào)查寧夏地區(qū)慢性乙型肝炎（Chronic hepatitis B，CHB）患者的ALT、HBV-DNA載量與血清標(biāo)志物水平之間的關(guān)聯(lián)性，探討HBV基因型、核苷（酸）類似物（nucleostide analogues，NAs）耐藥突變模式與HBV感染后慢性化、重癥化的關(guān)系，研究HLA-DRB1基因多態(tài)性與乙肝相關(guān)性疾病的關(guān)系。 方法隨機(jī)選取CHB患者283例，應(yīng)用化學(xué)發(fā)光微粒子免疫分析法定量檢測(cè)HBV血清學(xué)標(biāo)志物和熒光定量PCR檢測(cè)HBV-DNA載量，并對(duì)結(jié)果進(jìn)行相關(guān)性分析。從中選取134例住院患者的血清標(biāo)本應(yīng)用基因型特異性多對(duì)引物巢式PCR法進(jìn)行HBV基因分型，再使用直接測(cè)序法對(duì)分型結(jié)果進(jìn)行驗(yàn)證并檢測(cè)HBV的耐藥突變，，并針對(duì)不同的基因型進(jìn)行性別、年齡、肝功能、HBV-DNA載量及HBeAg水平的相關(guān)性分析，以及對(duì)不同耐藥突變模式CHB患者之間的臨床參數(shù)進(jìn)行分析比較。另選取87例CHB患者、78例肝硬化患者、31例肝癌患者和50例健康對(duì)照者作為研究對(duì)象，采用序列特異性引物-聚合酶鏈?zhǔn)椒磻?yīng)（polymerase chain reaction-sequence specificprimers PCR-SSP）方法對(duì)他們的HLA-DRB1等位點(diǎn)進(jìn)行基因分析研究。 結(jié)果（1）HBeAg陽(yáng)性患者較陰性患者的HBeAb水平和HBV-DNA載量均有顯著性差異（P0.001，P0.001）；女性的HBeAg和HBeAb水平均較男性高（P0.05，P0.01）；30-50歲組的CHB患者的HBV-DNA、HBeAg、HBeAb與30歲組、30-50歲組比較有顯著性差異（P0.01，P0.001，P0.01）；CHB患者中HBV DNA載量與HBeAg呈正相關(guān)（r=0.451，P0.001），與HBeAb呈正相關(guān)（r=0.434，P0.001)；ALT與HBsAg呈正相關(guān)（r=0.131，P0.05）。 （2）134例HBV感染者的血清標(biāo)本中，B基因型11例（8.2%），其中男10例，女1例；C基因型123例（91.8%），男87例，女36例。B型和C型之間的HBV-DNA和ALT水平有顯著差異（Z=3.23，P0.05；Z=0.19，P0.05）。全部標(biāo)本中有28例發(fā)生不同位點(diǎn)變異，變異率為20.9%，以單位點(diǎn)rtS213T突變?yōu)橹�，約占25.0%。 （3）與健康對(duì)照組相比，乙肝后肝硬化患者的DRB1*07、DRB1*12等位基因表達(dá)頻率明顯高于健康對(duì)照組，差異顯著（P0.05，OR=2.237，95%CI為1.689～2.961；P0.05，OR=2.317，95%CI為1.707～3.143）；漢族乙肝相關(guān)性疾病患者的DRB1*04、DRB1*13、DRB1*15等位基因表達(dá)頻率與漢族健康對(duì)照者的差異顯著（P0.05，OR=0.478，95%CI為0.367～0.623；P0.05，OR=0.462，95%CI為0.355～0.602；P0.05，OR=2.292，95%為1.599～3.283）。 結(jié)論（1）寧夏地區(qū)的慢性乙型肝炎患者的HBV-DNA載量與HBeAg呈正相關(guān)，兩者之間具有良好的一致性；但ALT水平與HBsAg水平呈正相關(guān)；女性患者的HBeAg濃度較男性高，其余指標(biāo)無顯著性差異。慢性乙型肝炎患者以30-50歲年齡階段的居多，且此組患者的HBV-DNA、HBeAg、HBeAb與其余年齡段組比較有顯著性差異。 （2）寧夏地區(qū)慢性乙型肝炎患者的基因型包括B型、C型，其中以C基因型為主，其次為B基因型；HBV基因型與HBV-DNA、ALT水平有關(guān)聯(lián)，和本研究中其他指標(biāo)比較無顯著差異；CHB患者主要對(duì)拉米夫定（LAM）與阿德福韋酯（ADV）耐藥，出現(xiàn)以單位點(diǎn)rtS213T為主的突變，并出現(xiàn)了混合位點(diǎn)突變。 （3）HLA-DRB1*07、DRB1*12可能是寧夏地區(qū)乙肝患者發(fā)生肝硬化的易感基因；HLA-DRBI*04和DRBI*l3可能是寧夏地區(qū)漢族人群的抗性基因；攜帶DRB1*15的漢族人群更容易發(fā)生乙肝相關(guān)性疾病。
[Abstract]:Objective To investigate the relationship between HBV - DNA load and serum marker level in patients with chronic hepatitis B ( HBV ) in Ningxia , and explore the relationship between HBV genotype , nucleoside ( acid ) analog ( NAs ) resistance mutation pattern and chronic and severe HBV infection , and study the relationship between HLA - DRB1 gene polymorphism and hepatitis B - related diseases .

Methods A total of 283 patients were randomly selected , and the HBV - DNA content was determined quantitatively by using the method of chemiluminescence , and the correlation of HBV - DNA level and HBV - DNA level was analyzed by direct sequencing .

Results ( 1 ) There was significant difference between HBeAg - positive patients and HBeAg - positive patients ( P0.001 , P0.001 ) .
The levels of HBeAg and HBeAg in women were higher than those in males ( P0.05 , P0.01 ) .
HBV - DNA , HBeAg , HBeAg , HBeAg , HBeAg , HBeAg , HBeAg , HBeAg , HBeAg and HBeAg were significantly different between 30 - 50 years old and 30 - 50 years old ( P0.01 , P0.001 , P0.01 ) .
The amount of HBV DNA was positively correlated with HBeAg ( r = 0.451 , P0.001 ) and positive correlation with HBeAg ( r = 0.434 , P0.001 ) .
ALT was positively correlated with HBsAg ( r = 0.131 , P0.05 ) .

( 2 ) Of 134 patients with HBV infection , 11 cases ( 8.2 % ) had genotype B , 10 were male and 1 female ;
There were 123 cases of genotype C ( 91.8 % ) , 87 males and 36 females . There was significant difference in HBV - DNA and ALT levels between genotype B and C ( Z = 3.23 , P0.05 ) .
Z=0.19,P0.05). In all the specimens , 28 cases had different site variation , and the mutation rate was 20 . 9 % . rtS213T mutation was dominant at the unit point , accounting for 25.0 % .

( 3 ) The frequency of DRB1 * 07 and DRB1 * 12 allele in patients with cirrhosis after hepatitis B was significantly higher than that in healthy control group ( P0.05 , OR = 2.237 , 95 % CI was 1.689 ~ 2.961 ) .
P0.05,OR=2.317,95%CI涓

本文編號(hào)：1963725