【作者】 李刚；

【导师】 侯凡凡； 张训；

【作者基本信息】 第一军医大学 ， 内科学， 2004， 硕士

【摘要】 背景： 自1964年Blumberg和Visnich发现乙型肝炎病毒表面抗原(HBsAg)以来，证实感染乙型肝炎病毒(HBV)的人数日趋增多，遍及世界各地。HBV是一种DNA病毒，属嗜肝DNA病毒科，是直径42nm的球形颗粒，又名Dane颗粒，有外壳和核心两部分。外壳厚7-8nm，有表面抗原(HBsAg)；核心直径27nm，含有部分双链、部分单链的环状DNA以及DNA聚合酶、核心抗原(HBcAg)及e抗原(HBeAg)。现己证实，乙型肝炎病毒除引起肝炎、肝硬化及肝癌外，还能引起肝外多器官病变。Combes等1971年首次报道了在1例膜性肾病患者的肾组织中检测到HBsAg，此后HBeAg、HBcAg也分别在1979年和1980年从肾组织中检出。HBV感染与肾小球肾炎的关系引起各国学者普遍关注，并为此做了大量工作。HBV感染可以导致肾小球损伤，引起乙肝病毒相关性肾炎(HBV-GN)，目前已成为一种共识。然而HBV-GN的确切发病机制目前尚欠清楚，通过HBV相关抗原(HBVAg)与相应抗体结合形成的免疫复合物致病可能是其主要途径，HBV直接感染肾脏亦可能扮演重要角色。我国是HBV感染的高流行区，明确HBV感染与HBV-GN之间的关系具有重要意义。 目的： 研究乙肝病毒感染与乙肝病毒相关性肾炎间的关系以及乙肝病毒相关性肾炎病人肾脏病变与肝脏病变之间的关系。 方法： 全部病例来自1993年4月到2003年9月南方医院肾内科病理实验室诊断的血清乙肝病毒抗原阳性的肾小球肾炎病例总计281例，其中男性197例，女性84例，平均29.03±14.05岁。选择资料完整的病例，对其中89例HBV-GN患者的血清病毒学、肾脏及肝脏病理学和常规实验室检查等结果进行回顾分析研究。肾组织病理改变的轻重，采用Katafuchi的半定量积分法进行判断。肾组织HBV DNA的检测采用直接原位PCR技术。肝脏病变按照2000年《病毒性肝炎防治方案》将炎症活动度(G)及纤维化程度(S)由轻到重分为0一4级和O~4期。结果: 一、一般情况:89例HBV-GN患者，肾活检时平均年龄26.20士15.13岁，其中男性70例，女性19例。平均发病年龄25.04士14.88岁，发病至肾活检的平均时间18，02士26.85月(88例)。病理类型:膜性肾病48例(53.9%)、系膜增生14例(巧.7%)、IgA肾病9例(10.1%)、局灶节段硬化7例(7.9%)、轻微病变4例(4.5%)、毛细血管内增生3例(3.4%)、增生硬化2例(2.2%)及膜增生2例(2.2%)。6例既往有明确的乙型肝炎病史。， 二、HBv病毒血症及其复制状态与肾炎的关系 z、251例血清HnvAg(Hs认g和/或HBeAg)阳性的肾炎患者中，确诊HBV-GN 89例(31.6%)，其中男性70例(35.5%)，显著多于女性(22.6%)(P<0，05)。 2、血清HBeAg阳性组HBV一GN的发生率显著高于阴性组 (p<0.01);同样地，血清HBV DNA定量>05copies/m一组HBv一GN的发生率亦显著高于定量<1 05coPies/ml组(p二0.001)。 3、HBV一GN患者中血清HBeAg阳性组与阴性组的尿蛋白定量、内生肌肝清除率无显著性差异。血清HBV DNA定量的水平亦对之无影响。但比较肾组织病理半定量积分，可以发现血清HBeAg阴性组肾小球硬化、间质纤维化、间质炎症及血管改变较重，不过二者总积分无显著差异。血清HBV DNA定量<105coPies/ml组肾小球节段损害及间质炎症程度较重，但总积分亦无显著差异。若选择单纯比较乙肝病毒相关性膜性肾病，则肾组织病理积分二组间无显著差异。 三、’肾组织局部HBV标志物的检出与肾脏病变的关系 1、免疫荧光检查发现，89例HBV一GN患者肾组织中均有免疫球蛋白和/或补体的沉积，伴HBsAg沉积51例，HBcAg沉积12例，二者同时沉积26例。HBVAg沉积部位大多在肾小球系膜区和/或毛细血管拌，与免疫球蛋白及补体的沉积部位完全相同，光镜下均可见到不同程度的肾小球病变。 2、HBv一GN患者肾组织局部HBcAg沉积阳性组的尿蛋白定量显著高于HBcAg阴性组(p<0.05)，而内生肌配清除率、肾组织病变程度及肾脏病理类型二组间无显著性差异。 3、肾组织局部HBV DNA的检出情况 (1)以原位PCR法检测了59例HBV一 GN患者肾组织局部的HBv DNA，其中阳性3一例，占52.5%。28例分布于肾小球内皮细胞、上皮细胞、系膜细胞及肾小管上皮细胞核，与肾小球内HBVAg的沉积部位大致相同。 (2)肾组织局部HBv DNA的检测阳性与否，肾组织病变程度无显著差异。 四、HBV一GN患者肝脏病变与肾脏病变的关系 1、HBV一GN患者中，血清HBeAg阳性组与阴性组相比较，肝功能、肝组织病变程度均无显著性差异。外周血HBV DNA定量是否大于l护copies/ml亦对之无明显影响。 2、HBV一GN患者肝组织病变程度不同的二组间24小时尿蛋白定量、内生肌配清除率及肾组织病变程度均无显著差异。 3、HBV一GN患者肝组织病变程度与肾组织病变程度无显著相关性。 结论: 一、HBV感染及其复制状态与HBV一GN的发生密切相关，但HBV的复制状态似乎并不明显影响HBV一GN患者肾、肝组织的病变程度。 二、HBV相关性循环免疫复合物在肾组织中的沉积可能是HBV一GN的主要发病机制;但HBV直接感染肾脏，原位表达HBVAg，形成原位免疫复合物，亦同样重要。 三、HBv一G更多还原

【Abstract】 Background:Since the discovery of the Australia antigen by Blumberg and Visnich in 1964,the cases of HBV infecton have been increasingly rising over the world.HBV is a kind of DNA virus,which belongs to hepadnavividae .It is a 42nm-sized sphere granule and called Dane partical which has an envelop and a core.The envelope is the hepatitis B surface antigen which thickness is 7-8nm. The core with 27nm diameter includes parts of double-chained and single-chained circular DNA, DNApolymerase, hepatitis B core antigen(HbcAg) and hepatitis B e antigen(HbeAg).That HBV can lead to other organs’lesions,such as different kind of glomerulonephropathy ,except hepatitis, liver cirrhosis and hepatocellular carcinoma has been confirmed. The detection of HbsAg in the kidney of a patient with membranous nephropathy was first reported by Combes in 1971 and HBeAg,HBcAg was found in kidneys one after the other in 1979 and 1980.Since then ,the researchers in many countries paid attension to the relationship between HBV infection and glomerulonephritis and have done more research work for it.Now,it is well accepted that HBV infection can lead to nephritis as a independent disease called hepatitis B virus associated glomerulonephritis(HBV-GN).But the pathogenetic mechanism of HBV-GN remains unclear.lt is suggested that HBV immune complexes play a main role in the pathogenesis of HBV-GN. That HBV may infect kidneys directly leading to nephritis is also another mechanism.There is a higher rate of HBV infection in our country and it’s significant to make clear the relationship between HBV infection and HBV-GN.Obstractive:To investigate the relationship between HBV infection and hepatitis B virus associated glomerulonephritis and the correlations between hepatic lesions and renal lesions in HBV-GN patients.Method:Two hundred and eighty-one consecutive cases of HBVAg-positive and histologically proven glomerulonephritis seen at the laboratory of Pathology in Nanfang Hospital from April 1993 to September 2003 were involved in this studied.Mean age 29.03 + 14.05 years of age. One hundred and nighty-seven were male and eighty-four female.Eighty-nine patients among these cases were diagnosed hepatitis B associated glomerulonephritis and their serological investigations,pathological findings of renal and liver biopsies and laboratory results were analyzed.The histological lesions of kidneys were semiquantitatively determined according to Katafuchi.We examined the paraffin section of kidney biopsies for HBV-DNA using in situ polymerase chain reaction(PCR). The degrees of liver inflammation (G) and fibrosis(S) were respectively divided into 0~4 according to the plans for prevention and treatment of viral hepatitis in our country.Results:l.CIinical findings:Mean age at the time of biopsy of the eighty-nine HBV-GN patients was 26.20?5.13 years.Seventy were male and nineteen female. Mean age at the discovery of the kidney disease was 25.04 + 14.88 years.The mean duration of the disease ,approximated from the time of discovery to biopsy,was 18. 02 + 26. 85 months(88 cases).Among these patients,there were 48 cases with MN,with the rate of 53.9%. 16 cases with MsPGN(17.9%) and 9 cases with IgA nephropothy(10.1%).Six patients had clinicalmanifestation of hepatitis in the past.2.The relationship between HBV serology , viral replication and nephritis.(l).The incidence of HBV-GN in male(35.5%) was significantly higher than that in female(22.6%) in 281 HBVAg positive patients(p<0.05).(2).The incidence of HBV-GN in groups of HBeAg-positive or HBV-DNA levels more than 105 copies/ml was significantly higher compared with groups of HBeAg-negative or HBV-DNA levels less than 105 copies/ml (p<0.001,p=0.001).(3).There was no significant difference between proteinura, creatinine clearance and renal pathological changes in groups of HBeAg-positive or HBV-DNA levels more than 105 copies/ml and groups of HBeAg- negative or HBV-DNA levels less than 105 copies/ml.3. The relationship between renal deposition of HBV and renal pathological changes.更多还原