發(fā)布時(shí)間：2018-03-05 08:51

  本文選題：肝炎病毒　切入點(diǎn)：乙型　出處：《延安大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：背景:HBV感染呈世界流行,全球大約有2.4億慢性HBV感染者,中國則有2000萬慢性感染者,故對(duì)慢性乙肝的防治任重道遠(yuǎn)。近年,由于乙型肝炎疫苗免疫的普及,HBV感染者的人口老齡化以及抗病毒藥物的應(yīng)用,低復(fù)制期患者比例增多。國內(nèi)外指南,指出此期僅需動(dòng)態(tài)觀察,但臨床實(shí)踐過程中,我們發(fā)現(xiàn)低復(fù)制期患者存在不同程度肝臟炎癥和纖維化,部分已達(dá)到抗病毒指征;另外,國內(nèi)外各大指南對(duì)此期的ALT、HBs Ag、HBVDNA以及組織學(xué)認(rèn)識(shí)意見不同;國內(nèi)一些學(xué)者認(rèn)為此期肝組織纖維化較重;還有學(xué)者認(rèn)為此期患者或許可以增加胰腺癌的風(fēng)險(xiǎn);基于對(duì)于這些爭(zhēng)議的思考,故展開本課題研究。目的:分析慢性HBV感染低復(fù)制期患者的肝臟病理特點(diǎn),探討與其臨床特征的關(guān)系;探索影響低復(fù)制期患者肝臟病理進(jìn)展的相關(guān)因素。方法:參照中國2015版《慢性乙型肝炎防治指南》低復(fù)制期的臨床診斷標(biāo)準(zhǔn),收集2013年10月至2016年12月在延安大學(xué)附屬醫(yī)院感染科住院并行肝活檢的125例低復(fù)制期患者的病例資料,回顧性地總結(jié)研究人群的肝臟病理特征,根據(jù)不同水平ALT、年齡、HBs Ag、HBV DNA及是否合并脂肪肝等因素進(jìn)行分組,分析這些因素與人口學(xué)、肝臟病理、生化指標(biāo)及血清乙型肝炎標(biāo)志物(HBV-M)之間關(guān)系,探討影響低復(fù)制期患者肝臟病理進(jìn)展的相關(guān)因素。采用spss20.0進(jìn)行統(tǒng)計(jì)分析,計(jì)量資料進(jìn)行正態(tài)性檢驗(yàn),正態(tài)分布資料采用?Х±S表示,非正態(tài)資料采用M±Q表示;構(gòu)成比應(yīng)用卡方檢驗(yàn),兩樣本總體均數(shù)比較,符合正態(tài)分布用t檢驗(yàn),不符合正態(tài)分布用mann-whitney U檢驗(yàn);多個(gè)樣本總體均數(shù)比較,符合正態(tài)分布且方差齊應(yīng)用方差分析,不符合正態(tài)分布或方差不齊采用kruskal-wallis H檢驗(yàn);應(yīng)用logistic回歸分析篩選風(fēng)險(xiǎn)因素;用受試者工作曲線(ROC)評(píng)估檢查指標(biāo)的預(yù)測(cè)價(jià)值。均以α=0.05為檢驗(yàn)水準(zhǔn),P0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:1.研究人群共125例,男性57例(45.6%),女性68例(54.4%),平均年齡為41.0±17.0歲,最小年齡18歲,最大年齡68歲;有乙肝家聚史85例(68.0%),無乙肝家聚史40例(32%);單純CHB組90例,CHB合并脂肪肝組35例。2.肝臟炎癥活動(dòng)度(G)分級(jí)為G1 32例(25.6%),G2 84例(67.2%),G3 9例(7.2%);肝臟纖維化分期(S)為S0 7例(5.6%)、S1 81例(64.8%)、S2 25例(20.0%)、S3 11例(8.8%)、S4 1例(0.8%)。無G0、G4患者。3.按G將研究人群分為輕微炎癥壞死組(G未達(dá)到2級(jí)者,G2)和明顯炎癥壞死組(G達(dá)到2級(jí)及2級(jí)以上者,≥G2),分別有32例、93例;兩組在性別、乙肝家聚史方面無差別(P值均0.05)。兩組的年齡、BMI、ALT、ALB、HBs Ag、HBc Ab亦無差異(P值均0.05)。兩組的DBil比較有差異(χ2=-2.031 P=0.042)。按S將其分為輕微纖維化組(S未達(dá)到2級(jí)者,S2)、明顯纖維化組(S達(dá)到2級(jí)及2級(jí)以上者,≥S2),分別有88例、37例。兩組的性別、乙肝家聚史構(gòu)成比無差別(P值均0.05)、兩組的年齡、BMI、ALT、DBil、HBs Ag、HBc Ab比較無差異(P值均0.05)。兩組的ALB比較有差異(P=0.008)。4.不同因素影響低復(fù)制期患者人口學(xué)特征、肝臟病理、生化指標(biāo)及血清HBV-M的特征變化分析4.1按不同ALT水平將研究人群分為ALT30U/L組和ALT≥30U/L組,分別有92例、33例。兩組的性別、G構(gòu)成比比較有差異(P=0.015)(P=0.039)。兩組的乙肝家聚史、S構(gòu)成比無差異(P值均0.05)。兩組的年齡、BMI、DBil、HBs Ag、HBc Ab比較均無差異(P值均0.05)。4.2按不同年齡水平將研究人群分為30歲組、30-39歲組及≥40歲組,分別有25例、32例、68例。三組在性別、乙肝家聚史、G、S構(gòu)成比方面比較無差異(P值均0.05)。三組的BMI、ALT、DBil、ALB、HBc Ab比較無差異(P值0.05)。三組的HBs Ag比較有差別(P=0.022),多重比較后,30歲組和≥40歲組的HBs Ag比較有差異(P=0.025),其余組間無差異(P值均0.05)。4.3按不同HBs Ag水平將研究人群分為3組,即3log10 IU/ml組、3-4log10IU/ml組、4 log10IU/ml組,分別有35例、68例、22例。三組在性別、乙肝家聚史、G、S方面無差別(P值均0.05)、三組的年齡、BMI、ALT、DBil、ALB、HBc Ab比較無差異(P值均0.05)。4.4按不同HBV DNA載量將研究人群分成3組:102IU/ml組、102-999IU/ml組、(1-2)×103 IU/ml組、分別有32例、69例、24例。三組在性別、乙肝家聚史、G、S方面比較無差異(P值均0.05)。三組的年齡、BMI、ALT、DBil、ALB、HBc Ab比較無差別(P值0.05)。4.5按是否合并脂肪肝將研究人群分為單純CHB組和CHB合并脂肪肝組,分別有90例、35例。兩組在性別、乙肝家聚史、G、S方面無差異(P值均0.05)。兩組的年齡、BMI、DBil、ALB、HBs Ag、HBc Ab比較亦無差異(p值均0.05)。5.采用Logistic回歸篩選危險(xiǎn)因素,發(fā)現(xiàn)DB、CⅣ、低水平ALT、GLB是影響低復(fù)制期患者肝臟明顯炎癥活動(dòng)發(fā)生的獨(dú)立預(yù)測(cè)因子。DB、CⅣ升高時(shí),提示肝臟明顯炎癥發(fā)生風(fēng)險(xiǎn)增大,而低水平ALT和GLB降低時(shí),提示明顯炎癥風(fēng)險(xiǎn)減小。6.應(yīng)用ROC評(píng)估檢查方法的預(yù)測(cè)價(jià)值,發(fā)現(xiàn)ALT、AST、TBil、DBil預(yù)測(cè)此期患者肝臟明顯炎癥活動(dòng)效能較差(P值均0.05)。LSM預(yù)測(cè)此期患者明顯肝纖維化的準(zhǔn)確率較高。FIB-4、AAR、APRI、HA、LN、CⅣ、PCⅢ等檢測(cè)方法對(duì)低復(fù)制期患者的肝纖維化診斷預(yù)測(cè)能力較差(p0.05)。結(jié)論:1.慢性HBV感染低復(fù)制期患者存在不同程度的肝臟炎癥活動(dòng)和纖維化,但以明顯炎癥活動(dòng)為主;2.DBil增高提示可能存在較明顯肝臟炎癥壞死;3.低于ALT的正常值上限患者仍存在肝臟組織炎癥改變,可考慮適當(dāng)下調(diào)ALT正常值上限,以提高診斷敏感性;4.不同水平年齡對(duì)慢性HBV感染低復(fù)制患者肝臟病理改變,血清HBs Ag隨著年齡的增長而下降,提示年齡越大時(shí),HBV復(fù)制可能減低。5.不同水平HBs Ag、HBV DNA以及合并脂肪肝對(duì)慢性HBV感染低復(fù)制患者肝臟病理改變和臨床特征無顯著影響。6.發(fā)現(xiàn)DB、CⅣ、低水平ALT、GLB是影響低復(fù)制期患者肝臟明顯炎癥活動(dòng)發(fā)生的獨(dú)立預(yù)測(cè)因子。當(dāng)DBil、CIV、GLB升高和ALT高值時(shí),提示肝臟明顯炎癥發(fā)生的風(fēng)險(xiǎn)增大;7.LSM預(yù)測(cè)低復(fù)制期患者明顯肝纖維化準(zhǔn)確率較高,有一定的參考價(jià)值;而FIB-4、APRI、AAR三種無創(chuàng)模型及血清肝纖維化指標(biāo)預(yù)測(cè)明顯肝纖維化能力較差;
[Abstract]:Background: HBV infection is the world of fashion, around the world have 240 million persons infected with chronic HBV, China 20 million have chronic infection and so on chronic hepatitis B prevention work. In recent years, due to the popularity of hepatitis B vaccine immunization, the aging population of HBV infection and application of antiviral drugs, the proportion of patients with low replication stage increased. This guide at home and abroad, pointed out that only the dynamic observation, but the clinical practice, we found that patients with low replication of liver inflammation and fibrosis in different degree, some have reached the antiviral indication; in addition, the major domestic and international guidelines in this period of ALT, HBs, Ag, HBVDNA and histological understanding of different opinions; some domestic scholars believe that this period of liver fibrosis is more serious; some scholars believe that these patients may increase the risk of pancreatic cancer; think about these disputes based on the research of the folio exhibition. Objective: to analyze the course The pathological characteristics of the patients with low replication of chronic HBV infection, to investigate the relationship and clinical characteristics; explore the related factors affecting the progress of low copy in patients with liver pathology. Methods: according to the clinical diagnostic criteria Chinese 2015 edition of < chronic hepatitis B > low replication, collected from October 2013 to December 2016 in Affiliated Hospital of Yan'an University hospital infection in 125 cases low replication in patients with parallel liver biopsy. The clinical data were retrospectively summarized liver pathological features of the study population, according to the different levels of ALT, HBs Ag, HBV DNA, age, and whether complicated with fatty liver and other factors were divided into two groups, analysis of these factors and demographic, liver pathology, biochemical indexes and serum markers of hepatitis B (HBV-M) the relationship between the factors related to the progress of low copy in patients with liver pathology. Spss20.0 was used for statistical analysis, measurement data for normality Test of normal distribution data using the? * + S said, non normal data using M + Q; constituent ratio by chi square test two samples were compared with normal distribution, using t test, do not accord with normal distribution test with Mann-Whitney U; multiple samples were compared with. Normal distribution and homogeneity of variance analysis, does not meet the normal distribution and homogeneity of variance using Kruskal-Wallis H test; logistic regression analysis was applied to screening risk factors; receiver operating curve (ROC) predictive value evaluation indexes. To test the level of a =0.05 P0.05, the difference was statistically significant. Results study population: 1. a total of 125 cases, 57 cases were male (45.6%), 68 cases were female (54.4%), the average age was 41 + 17 years old, the minimum age of 18 years, the maximum age of 68 years; 85 cases of hepatitis B family history (68%), 40 cases of hepatitis B without family history (32%); CHB group of 90 cases, CHB with fat 鑲濈粍35渚，

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