慢性HBV感染低复制期患者肝脏病理与临床特征研究

发布时间：2018-03-05 08:51

  本文选题：肝炎病毒　切入点：乙型　出处：《延安大学》2017年硕士论文　论文类型：学位论文

【摘要】：背景:HBV感染呈世界流行,全球大约有2.4亿慢性HBV感染者,中国则有2000万慢性感染者,故对慢性乙肝的防治任重道远。近年,由于乙型肝炎疫苗免疫的普及,HBV感染者的人口老龄化以及抗病毒药物的应用,低复制期患者比例增多。国内外指南,指出此期仅需动态观察,但临床实践过程中,我们发现低复制期患者存在不同程度肝脏炎症和纤维化,部分已达到抗病毒指征;另外,国内外各大指南对此期的ALT、HBs Ag、HBVDNA以及组织学认识意见不同;国内一些学者认为此期肝组织纤维化较重;还有学者认为此期患者或许可以增加胰腺癌的风险;基于对于这些争议的思考,故展开本课题研究。目的:分析慢性HBV感染低复制期患者的肝脏病理特点,探讨与其临床特征的关系;探索影响低复制期患者肝脏病理进展的相关因素。方法:参照中国2015版《慢性乙型肝炎防治指南》低复制期的临床诊断标准,收集2013年10月至2016年12月在延安大学附属医院感染科住院并行肝活检的125例低复制期患者的病例资料,回顾性地总结研究人群的肝脏病理特征,根据不同水平ALT、年龄、HBs Ag、HBV DNA及是否合并脂肪肝等因素进行分组,分析这些因素与人口学、肝脏病理、生化指标及血清乙型肝炎标志物(HBV-M)之间关系,探讨影响低复制期患者肝脏病理进展的相关因素。采用spss20.0进行统计分析,计量资料进行正态性检验,正态分布资料采用?Х±S表示,非正态资料采用M±Q表示;构成比应用卡方检验,两样本总体均数比较,符合正态分布用t检验,不符合正态分布用mann-whitney U检验;多个样本总体均数比较,符合正态分布且方差齐应用方差分析,不符合正态分布或方差不齐采用kruskal-wallis H检验;应用logistic回归分析筛选风险因素;用受试者工作曲线(ROC)评估检查指标的预测价值。均以α=0.05为检验水准,P0.05为差异有统计学意义。结果:1.研究人群共125例,男性57例(45.6%),女性68例(54.4%),平均年龄为41.0±17.0岁,最小年龄18岁,最大年龄68岁;有乙肝家聚史85例(68.0%),无乙肝家聚史40例(32%);单纯CHB组90例,CHB合并脂肪肝组35例。2.肝脏炎症活动度(G)分级为G1 32例(25.6%),G2 84例(67.2%),G3 9例(7.2%);肝脏纤维化分期(S)为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%)。无G0、G4患者。3.按G将研究人群分为轻微炎症坏死组(G未达到2级者,G2)和明显炎症坏死组(G达到2级及2级以上者,≥G2),分别有32例、93例;两组在性别、乙肝家聚史方面无差别(P值均0.05)。两组的年龄、BMI、ALT、ALB、HBs Ag、HBc Ab亦无差异(P值均0.05)。两组的DBil比较有差异(χ2=-2.031 P=0.042)。按S将其分为轻微纤维化组(S未达到2级者,S2)、明显纤维化组(S达到2级及2级以上者,≥S2),分别有88例、37例。两组的性别、乙肝家聚史构成比无差别(P值均0.05)、两组的年龄、BMI、ALT、DBil、HBs Ag、HBc Ab比较无差异(P值均0.05)。两组的ALB比较有差异(P=0.008)。4.不同因素影响低复制期患者人口学特征、肝脏病理、生化指标及血清HBV-M的特征变化分析4.1按不同ALT水平将研究人群分为ALT30U/L组和ALT≥30U/L组,分别有92例、33例。两组的性别、G构成比比较有差异(P=0.015)(P=0.039)。两组的乙肝家聚史、S构成比无差异(P值均0.05)。两组的年龄、BMI、DBil、HBs Ag、HBc Ab比较均无差异(P值均0.05)。4.2按不同年龄水平将研究人群分为30岁组、30-39岁组及≥40岁组,分别有25例、32例、68例。三组在性别、乙肝家聚史、G、S构成比方面比较无差异(P值均0.05)。三组的BMI、ALT、DBil、ALB、HBc Ab比较无差异(P值0.05)。三组的HBs Ag比较有差别(P=0.022),多重比较后,30岁组和≥40岁组的HBs Ag比较有差异(P=0.025),其余组间无差异(P值均0.05)。4.3按不同HBs Ag水平将研究人群分为3组,即3log10 IU/ml组、3-4log10IU/ml组、4 log10IU/ml组,分别有35例、68例、22例。三组在性别、乙肝家聚史、G、S方面无差别(P值均0.05)、三组的年龄、BMI、ALT、DBil、ALB、HBc Ab比较无差异(P值均0.05)。4.4按不同HBV DNA载量将研究人群分成3组:102IU/ml组、102-999IU/ml组、(1-2)×103 IU/ml组、分别有32例、69例、24例。三组在性别、乙肝家聚史、G、S方面比较无差异(P值均0.05)。三组的年龄、BMI、ALT、DBil、ALB、HBc Ab比较无差别(P值0.05)。4.5按是否合并脂肪肝将研究人群分为单纯CHB组和CHB合并脂肪肝组,分别有90例、35例。两组在性别、乙肝家聚史、G、S方面无差异(P值均0.05)。两组的年龄、BMI、DBil、ALB、HBs Ag、HBc Ab比较亦无差异(p值均0.05)。5.采用Logistic回归筛选危险因素,发现DB、CⅣ、低水平ALT、GLB是影响低复制期患者肝脏明显炎症活动发生的独立预测因子。DB、CⅣ升高时,提示肝脏明显炎症发生风险增大,而低水平ALT和GLB降低时,提示明显炎症风险减小。6.应用ROC评估检查方法的预测价值,发现ALT、AST、TBil、DBil预测此期患者肝脏明显炎症活动效能较差(P值均0.05)。LSM预测此期患者明显肝纤维化的准确率较高。FIB-4、AAR、APRI、HA、LN、CⅣ、PCⅢ等检测方法对低复制期患者的肝纤维化诊断预测能力较差(p0.05)。结论:1.慢性HBV感染低复制期患者存在不同程度的肝脏炎症活动和纤维化,但以明显炎症活动为主;2.DBil增高提示可能存在较明显肝脏炎症坏死;3.低于ALT的正常值上限患者仍存在肝脏组织炎症改变,可考虑适当下调ALT正常值上限,以提高诊断敏感性;4.不同水平年龄对慢性HBV感染低复制患者肝脏病理改变,血清HBs Ag随着年龄的增长而下降,提示年龄越大时,HBV复制可能减低。5.不同水平HBs Ag、HBV DNA以及合并脂肪肝对慢性HBV感染低复制患者肝脏病理改变和临床特征无显著影响。6.发现DB、CⅣ、低水平ALT、GLB是影响低复制期患者肝脏明显炎症活动发生的独立预测因子。当DBil、CIV、GLB升高和ALT高值时,提示肝脏明显炎症发生的风险增大;7.LSM预测低复制期患者明显肝纤维化准确率较高,有一定的参考价值;而FIB-4、APRI、AAR三种无创模型及血清肝纤维化指标预测明显肝纤维化能力较差;
[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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