免疫细胞化学法检测乙型肝炎产妇分娩的死胎心脏组织乙型肝炎核心抗原的表达

目的 :观察乙型肝炎病毒 ( HBV)通过产妇传播在胎儿心脏组织中表达的情况。方法 :采集 40例乙型肝炎产妇分娩的死胎 ,常规尸检 ,取心脏组织 ,免疫细胞化学法检测乙型肝炎核心抗原 ( HBc Ag) ;回访孕妇产前静脉血 HBV的检测结果 ;采用百分率行 χ2检验。结果 :HBc Ag阳性颗粒在死胎的心内膜及心脏血管中呈点状及灶状分布 ,心肌细胞核不着色。乙型肝炎表面抗原 ( HBs Ag)、乙型肝炎 e抗原 ( HBe Ag)、乙型肝炎核心抗体( HBc Ab)皆为阳性的孕妇较 HBV单项阳性或 HBs Ag、乙型肝炎 e抗体 ( HBe Ab)、HB-c Ab皆为阳性的孕妇分娩的死胎心脏组织中 HBc Ag阳性率明显升高 ( P<0 .0 5) ;HBV单项阳性与 HBs Ag、HBe Ab、HBc Ab皆为阳性的孕妇分娩的死胎心脏组织中 HBc Ag阳性率比较 ,无显著差异 ( P>0 .0 5)。结论 :孕妇静脉血 HBs Ag、HBe Ag、HBc Ab皆为阳性是乙型肝炎病毒通过母婴垂直传播在胎儿心脏组织中表达的高危因素。     

免疫组化方法观察乙肝病毒感染肝星状细胞的研究

目的 研究HBV能否体外感染LX-2细胞,以期为阐明慢性乙肝的致病机制提供新的实验依据.方法 体外培养LX-2细胞细胞数目达到106/培养瓶时,用HBV感染者的血清进行感染,HBVDNA终浓度分别为104、105、106、107拷贝/mL,同一浓度的感染时间均为24、48和72 h.按照观察时间点收取细胞,免疫组织化学法(DAB显色)测定HBV在细胞内是否表达乙肝表面抗原(HB-sAg)和乙肝核心抗原(HBcAg).结果 用免疫组化方法标记HBsAg和HBcAg时,LX-2细胞中未发现阳性颗粒;HepG2.2.15细胞中有少量棕黄色颗粒,位于胞质中;慢性乙肝患者肝组织中可见大量棕黄色颗粒.结论 在体外培养中HBV不能感染LX-2细胞和进行抗原表达.     

慢性乙型肝炎患者肝细胞内HBcAg分布与血清病毒学指标的相关性研究

目的探讨慢性乙型肝炎患者肝细胞内HBcAg分布规律与血清病毒学指标的相关性。方法对958例慢性乙型肝炎患者的血清学、病毒学、免疫组织化学等资料进行对比分析。结果在肝细胞内HBcAg不同分布类型之间,血清HBeAg阳性率及HBV DNA载量均存在显著性差异（χ2值分别为364.01和417.41,P〈0.001）。其中,此两项指标以HBcAg核型和混合型分布组最高,HBcAg阴性组最低,而HBcAg浆型分布组的HBeAg阳性率及HBV DNA载量则介于上述两组之间。结论 HBcAg在受染肝细胞内的分布与血清病毒学指标之间具有明显的相关性,随着HBcAg分布态势由受染肝细胞核向细胞浆漂移到最终不能检测到,HBeAg阳性率及HBV DNA载量呈逐渐降低的趋势。     

Hepatitis B e antigen-associated membranous nephropathy

A case of hepatitis B virus (HBV)-associated membranous nephropathy (MN) is presented in an 18-year-old Korean male, whose renal disease had begun 9 years previously. He was positive for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and antibody to hepatitis B core antigen (anti-HBc) in the serum. By immunofluorescence, HBeAg staining was noted in glomerular deposits in association with IgG, C3 and Clq, while neither HBsAg nor HBcAg was found in the glomerular deposits. The presence of glomerular HBeAg staining by FITC-monoclonal anti-HBe F(ab')2 fragments has been reported before, but never in non-Japanese patients. The demonstration of HBeAg in both the glomerular deposits and serum in this case supports the causal relationship of HBeAg and HBV-associated MN.     

Membranous nephropathy in 52 hepatitis B surface antigen (HBsAg) carrier children in Taiwan

To elucidate the prognosis and the causative viral antigens of hepatitis B virus (HBV)-associated childhood membranous nephropathy (MN), the clinical course and glomerular HBV antigens were studied in 52 HBsAg carrier children with MN (40 boys, 12 girls). With Fab fragments of monoclonal antibodies, hepatitis Be antigen (HBeAg) was detected in the glomerular deposits in 41 (95%) of 43 cases but HBsAg and hepatitis B core antigen (HBcAg) in none. HBeAg was detected in sera from 43 (93%) of 46 children examined. These results suggest that HBeAg plays an important role in the development of MN in HBsAg carrier children. During the follow-up period (mean, 4 years), complete remission was found in 64% and 92% of the patients followed for one and seven years, respectively; only one child had mild renal function impairment. These findings suggest a favorable outcome of HBsAg-associated childhood MN. The patient's age, disease duration, amount of glomerular deposit, focal sclerosis and disease stage appeared to affect the clinical course. HBsAg seroconversion to HBsAg-negative occurred in seven cases, and all (100%) had quick remission in two years. In patients with persistent HBsAg carriage, serum HBeAg status alone did not correlate with remission rate and remission occurred usually before the HBeAg seroconversion to anti-HBe. These findings, together with the predominant horizontal infection in these children in contrast to the frequent vertical (perinatal) transmission from HBsAg carrier mothers in HBsAg carriers in Taiwan, suggest that factors other than HBeAg per se may also play important roles.     

精子细胞乙型肝炎病毒核心抗原流式细胞检测方法的建立

目的探讨建立流式细胞分析术对精子细胞乙型肝炎病毒核心抗原(HBcAg)定性、定量检测的诊断方法。方法收集62例乙型肝炎患者精液标本,制备成精子细胞单细胞悬液,用荧光标记的小鼠抗HBcAg单克隆抗体与标本细胞充分反应后,应用流式细胞分析术进行定性、定量检测,并制定诊断标准。结果该方法对乙型肝炎患者精子细胞HBcAg定性阳性检出率即敏感度为96.77%,对10例健康对照标本HBcAg定性阴性检出率即特异度为100%,阳性、阴性预测值均为100%,准确度97.22%。该方法精子细胞中HBcAg含量以精子细胞HBcAg指数(SHBcI)表示。乙型肝炎组和对照组SHBcI分别为(5.8777±8.9114)和(0.2800±0.1549),差异具有统计学意义;高病毒载量(HBV DNA≥106拷贝/ml)组SHBcI明显高于低病毒载量(HBV DNA106拷贝/ml)组;24例拉米夫定治疗者,治疗后SHBcI明显下降,分别为(8.49±5.13)和(4.18±3.17)。结论该方法能够对精子细胞HBcAg定性兼定量进行诊断,该方法建立对于预测乙型肝炎父婴传播以及阻断治疗都将起到指导作用。     

Differences in Tissue Expression of HBV Markers in Children with HBV-Associated Glomerulonephritis

Abstract

Background/Aims: Hepatitis B virus-associated glomerulonephritis (HBV-GN) is recognized as one of the major secondary nephropathies in HBV high-risk areas. To determine possible differences in the expression of HBV immune markers in tissues, we retrospectively examined HBV immune markers in the serum, renal tissues, and liver tissues in 132 HBV-GN children. Methods: All 132 patients had biopsy-proven HBV-GN including the presence of positive HBV antigens in the kidney. Serum-HBV immune markers were tested by an enzyme-linked immunosorbent assay. Renal and liver biopsies were done in 26 patients. All renal tissues were examined for HBV immune markers by immunofluorescence, and liver tissues were examined by immunohistochemistry. Results: Among the 132 patients, all showed varying degrees of kidney injury. Serum hepatitis B envelope antigen (HBeAg) was positive in 80 patients and negative in 52 patients. The positivity rate of Hepatitis B core antigen in renal tissue was statistically higher in serum HBeAg (?) than in serum HBeAg (+) patients (96.2% vs. 55.0%). Furthermore, there was no relationship between the presence of hepatitis B surface antigen and HBcAg in liver and renal tissue. Conclusion: HBV markers are not consistently present in serum, renal tissues, and liver tissues in children with HBV-GN.     

不明原因肝病患者肝组织HBV及HCV抗原的检测及临床和病理特点

目的了解不明原因肝病患者中HBV及HCV隐匿性感染所占的比例及临床、病理特点。方法对31例不明原因肝病患者,采用酶联免疫吸附试验（ELISA）检测血清乙型肝炎病毒标志物（HBV-M）（HBsAg、抗-HBs、HBeAg、抗-HBe和抗-HBc）及丙型肝炎病毒抗体;血清HBV DNA采用荧光定量PCR法检测,HCV RNA采用RT-PCR法检测;应用免疫组织化学二步法检测肝组织中的HBsAg、HBcAg、HCV抗原,并进行常规病理检查。结果肝组织HBV抗原阳性者11例（35.5%）;HBV、HCV抗原均阳性者10例（32.3%）,全阴性者10例（32.3%）。存在HBV隐匿性感染的21例患者中,慢性肝炎患者7例,肝硬化患者12例,肝细胞性肝癌患者2例。结论HBV、HCV感染为不明原因肝病的主要原因,尤其是HBV感染。HBV隐匿性感染与慢性肝炎、肝硬化、肝癌关系密切,应引起重视。     

IgA nephropathy associated with hepatitis B virus antigenemia

The pathogenetic ability of hepatitis B virus (HBV) antigenemia to induce IgA nephropathy was examined in 10 patients with IgA nephropathy and HBV antigenemia. They had no previous history of liver diseases and their liver function tests were normal. All were positive for hepatitis + surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBcAg) with high titers, thereby indicating they were persistent carriers of HBV. Immunoperoxidase studies using monospecific polyclonal antibodies revealed HBcAg and HBsAg in the nuclei and cytoplasm of glomerular mesangial cells in 8 patients. These findings suggest immune complexes involving HBcAg and HBsAg may induce IgA nephropathy in persons who carry HBV.     

Histopathology and clinical correlates of end-stage hepatitis B cirrhosis: a possible mechanism to explain the response to antiviral therapy.

In chronic liver disease associated with histological necroinflammation, clinical severity is frequently greater in those with higher grades of activity. Conventional wisdom assumes that necroinflammation is mild or absent in patients with end-stage hepatitis B virus (HBV) cirrhosis due to the frequent presence of mildly elevated aminotransferase levels, the absence of hepatitis B e antigen (HBeAg), and low or undetectable HBV deoxyribonucleic acid (DNA) levels. However, a histopathologic analysis of such patients has not been undertaken. The aims of this study were 1) to assess severity and histological features of inflammation, 2) to correlate the severity of inflammation with biochemical and virologic parameters, and 3) to define the relationship between inflammation and clinical severity in explanted livers from patients undergoing liver transplantation for HBV cirrhosis. Characteristics of 34 consecutive patients undergoing liver transplantation for HBV cirrhosis were correlated with inflammation and immunohistological findings in the explanted livers. High-grade inflammation (grades 3 and 4) was found in many cases (47.1% interface hepatitis; 14.8% lobular inflammation; and 20.6% portal inflammation). The presence of positive cytoplasmic staining for hepatitis B core antigen (HBcAg) was associated with grade 3 or 4 interface hepatitis (P = .046) and lobular hepatitis (P = .005). There was no correlation between inflammatory activity and age, Asian ethnicity, aminotransferase levels, total bilirubin levels, HBeAg seropositivity, and detectable HBV DNA level. Patients with high-grade inflammation had greater degrees of hepatic decompensation. In conclusion, high-grade inflammation is common in end-stage HBV cirrhosis, but it is not readily detected by biochemical and virologic parameters. High-grade inflammation is associated with a greater degree of hepatic decompensation.     

乙型肝炎病毒DNA与IgA肾病发病的关系

目的：探讨乙型肝炎病毒(HBV)感染与IgA肾病发病的关系。方法：50例血清HBV标志或肾组织HBV抗原阳性的IgA。肾病患者作为研究对象，应用原位分子杂交技术和Souther blot技术检测肾组织中HBV DNA。结果：50例IgA肾病患者中，血清HBsAg阳性17例(34％)；肾组织HBAg阳性48例(96％)，HBAg在肾小球中阳性率为82％(41／50)，其中HBsAg为58％(29／50)，HBcAg为42％(21／50)；除了肾小球，47例(94％)患者BsAg和HBcAg。肾小管上皮细胞亦有阳性沉积，分别为28例(56％)和39例(78％)；原位分子杂交证实50例患者肾组织HBV DNA阳性率为92％(46／50)，其中肾小管上皮细胞、肾小球细胞HBV DNA阳性率分别为72％(36／50)和82％(41／50)。Southem blot技术证实在50例患者肾组织中34例有整合型HBV DNA，阳性率为68％。结论：HBV感染与IgA肾病的发病密切相关，HBV可能直接感染肾组织并原位表达HBV DNA而参与了IgA肾病的发病。     

The existence and significance of hepatitis B virus DNA in glomerulonephritis

Summary: In order to investigate the role of hepatitis B virus (HBV) in the pathogenesis of glomerulonephritis 50 cases of glomerulonephritis with HBV antigenaemia and/or hepatitis B antigen (HBAg) detected by immunohistochemistry in renal tissue were collected. the distribution and localization of HBV DNA were observed by using in situ hybridization. In addition, Southern blot analysis was performed on 23 of the 50 cases in order to reveal the state of renal HBV DNA. Thirty-six cases (72%) were found to be HBV DNA positive by in situ hybridization, which localized in the nucleus of tubular cells. In 26 cases HBV DNA was detectable in the nucleus of glomerular mesangial and epithelial cells as well as the mesangial matrix. Seventeen of the 23 cases were proved to be HBV DNA positive in Southern blot analysis (82%). Three of these cases were identified with non-replicating free HBV DNA, while 14 cases were the integrated form. the results of this study showed that the renal tissue was infected with HBV; however, it was considered that it may be possible that the HBAg deposited on glomeruli was not only from circulation but also from the HBV infected glomerular cells although the evidence of this is not conclusive. In addition to the humoral immune injury mediated by HBAg-hepatitis B antibody (HBAb) immune complexes the cellular immune injury mediated by target antigen (hepatitis B core antigen; HBcAg) might be also involved in the pathogenesis of HBV glomerulonephritis (GN) associated GN.     

Recurrence-free long-term survival after liver transplantation for hepatitis B using interferon-alpha pretransplant and hepatitis B immune globulin posttransplant.

OBJECTIVE: The authors determined whether pretransplant reduction of hepatitis B virus (HBV) load using alpha-interferon-2b (IFN) and passive immunoprophylaxis using hepatitis B immunoglobulin (HBIg) posttransplantation can prevent HBV recurrence in patients undergoing liver transplantation (LT) for HBV cirrhosis. SUMMARY BACKGROUND DATA: Liver transplantation in patients with HBV cirrhosis is associated with a high rate of recurrence and reduced survival. In patients with evidence of replicating virus (HBV-DNA or hepatitis B e antigen [HBeAg]-positive serum or both), recurrence is nearly universal. Passive immunoprophylaxis with HBIg alone is not effective in preventing HBV recurrence posttransplant, especially in patients with evidence of active viral replication pretransplant. Higher doses of HBIg posttransplant has reduced recurrence rates to 30% to 50%. Lamivudine, a nucleoside analogue that has shown early promise, also is associated with significant HBV recurrence. The authors report a reliable method of preventing viral recurrence in patients even with evidence for active HBV replication pretransplant. METHODS: Pretransplant patients with evidence of replicating HBV were given IFN starting at 1 million IU 3 times per week subcutaneously. This dose was increased to 2 and then 3 million IU 3 times per week when patient's side effects permitted and was maintained until the patient underwent a LT. All patients were tested every 4 weeks for hepatitis B surface antigen (HBsAg), HBeAg, and HBV-DNA. When patients became negative for HBeAg and HBV-DNA, they were listed for LT. Patients that were only HBsAg positive were listed immediately and received a LT without prior IFN treatment. Post-LT, all patients began receiving HBIg 2000 IU (10 mL) daily from days 1 to 20 and then weekly for the first 2 years. After 2 years, all patients received 2000 IU (10 mL) monthly. Additional HBIg immunoprophylaxis was given during intense immunosuppression for rejection. Posttransplant serum was tested for HBsAg, HBeAg, and HBV-DNA in all patients 1 week, 1 month, and every 3 months thereafter. Liver biopsies were done at least yearly and when liver enzymes were abnormal and were always tested for HBsAg and HBcAg by immunoperoxidase. RESULTS: Thirteen patients with decompensated HBV cirrhosis were transplanted. Pretransplant, eight patients had evidence of active viral replication at the initial assessment (HBeAg or HBV-DNA-positive serum or both). All eight were successfully treated with IFN (median duration, 24 weeks; range, 8-53) and converted to a negative status before transplantation. Side effects from IFN were minimal and well tolerated, except in one patient who required 6 million IU to convert to a nonreplicating status. The five patients that were only HBsAg positive were not treated with IFN pretransplant. After surgery, HBIg given as described achieved consistently serum levels greater than 1000 IU/L. Twelve of the 13 patients are alive with normal liver function and without serologic evidence of HBV recurrence at a median follow-up of 32 months (range, 9-56 months). None have evidence of HBV recurrence as measured by serum HBsAg/HBeAg/HBV-DNA at recent follow-up. The sera of the seven longest survivors has tested negative for HBV-DNA using the polymerase chain reaction method. In addition, a liver biopsy was obtained in six of these patients, the results of which also tested negative for HBV-DNA using polymerase chain reaction. Liver biopsy specimens have been negative for the presence of HBsAg and HBcAg by immunoperoxidase staining in all 12 patients. CONCLUSION: A reduction of viral load pretransplant with IFN and posttransplant HBIg prevents recurrence of hepatitis B and permits LT for HBV cirrhosis, even in patients with evidence of replicating virus. The IFN pretransplant was well tolerated, and the small frequent dosing of HBIg posttransplant did not cause side effects while achieving serum levels > 1000 IU/L.     

PEG-干扰素α-2a治疗低转氨酶乙型肝炎患者的回顾性研究

目的对于PEG-干扰素α-2a（PEG—IFNα-2a）治疗的低转氨酶水平慢性乙型肝炎患者进行回顾性研究。方法对治疗满48周并于治疗前完成肝活检的乙型肝炎患者,取用药后第12周、24周、48周为观察点,记录乙型肝炎病毒血清标志物与HBVDNA的变化情况,并分析其应答与肝组织炎症程度（G分级）、肝细胞HBcAg分布的相关程度。结果按炎症级别分组之HBeAg阳性组：治疗48周时G1组总有效率20％（2／10）,G2组总有效率56．25％（9／16）,G3组100％（6／6）;HBeAg阴性组炎症级别G1组10％（1／10）,G2组62．5％（5／8）,G3组100％（2／2）。按照肝细胞HBcAg表达分组之HBeAg阳性组：48周时浆型表达总有效率80％（8／10）,混合型表达组总有效率42．1％（8／19）,阴性表达组100％（3／3）。HBeAg阴性组：浆型分布组DNA阴转率为37．5％（3／8）,混合型组为28．57％（2／7）,阴性组为60％。结论无论按照炎症还是肝细胞HBcAg表达分组比较,最初统计学处理后发现各个级别分组所得数据未见明显差异（包括HBeAg阳性与阴性组）。加入时间因素后显示随时间延长,高炎症水平、HBcAg的阴性表达和（或）浆型表达会有更高的疗效。     

慢性乙型肝炎患者不同免疫状态下外周血T淋巴细胞程序性死亡受体1表达与乙型肝炎病毒DNA载量及丙氨酸氨基转移酶水平的相关性

目的探讨慢性乙型肝炎（CHB）患者不同免疫状态下外周血T淋巴细胞程序性死亡受体1（PD-1）表达与乙型肝炎病毒（HBV）DNA载量及丙氨酸氨基转移酶（ALT）水平的相关性。 方法选取2017年1月至2018年3月于内蒙古医科大学附属医院接受治疗的CHB患者118例,依据患者不同免疫状态分成3组,分别为HBV e抗原（HBeAg）阴性组（25例）、免疫活化组（67例）和免疫耐受组（26例）;同时选取同期在本院健康体检者50例作为对照组。全自动生化分析仪检测肝功能,ELISA法检测HBV核心抗体（HBcAb）、HBV表面抗原（HBsAg）、HBV e抗体（HBeAb）、HBeAg和HBV表面抗体（HBsAb）含量,荧光定量PCR检测患者HBV DNA载量,流式细胞仪检测血清表达PD-1的CD8⁺ T、CD4⁺ T淋巴细胞含量。 结果免疫活化组、HBeAg阴性组患者血清表达PD-1的CD8⁺ T、CD4⁺ T含量分别为（7.48 ± 1.76）%、（7.48 ± 1.76）%和（10.58 ± 1.95）%、（8.38 ± 1.85）%,均高于对照组[（3.22 ± 1.53）%、（4.05 ± 1.76）%]和免疫耐受组[（4.26 ± 1.89）%、（3.86 ± 1.89）%],差异均有统计学意义（F = 12.084、P = 0.015,F = 13.297、P = 0.032）;免疫活化组、HBeAg阴性组患者HBV DNA载量分别为（7.02 ± 1.13）log₁₀拷贝/ml和（5.77 ± 1.25）log₁₀拷贝/ml,低于免疫耐受组患者（8.18 ± 1.08）log₁₀拷贝/ml,差异有统计学意义（F = 11.652、P = 0.006）;免疫活化组、HBeAg阴性组患者血清ALT、总胆红素含量分别为（193.02 ± 7.39）IU/ml、（50.06 ± 2.18）mmol/L和（179.14 ± 7.62）IU/ml、（43.65 ± 2.27）mmol/L,均高于对照组[（12.71 ± 6.19）IU/ml、（13.07 ± 2.19）mmol/L]和免疫耐受组[（23.19 ± 6.82）IU/ml、（16.54 ± 2.30）mmol/L],差异均有统计学意义（F = 10.906、P = 0.027,F = 9.583、P = 0.019）;Pearson相关分析显示,免疫耐受组、免疫活化组及HBeAg阴性组患者血清内表达PD-1的CD8⁺ T、CD4⁺ T含量和血清ALT含量无相关性（r =－0.170、0.046、0.068、－0.231、0.048、0.005,P = 0.443、0.750、0.761、0.292、0.709、0.912）,与血清HBV DNA载量亦无相关性（r = －0.049、0.107、0.104、－0.301、0.019、0.279,P = 0.810、0.440、0.681、0.201、0.883、0.221）。 结论CHB患者机体免疫状态和血清内T细胞PD-1表达量相关,患者肝脏炎症受损对PD-1表达有重要影响,而HBV DNA载量非主要影响因素。     

肝移植术后HBV再感染的治疗

目的分析肝移植术后乙型肝炎病毒（HBV）再感染患者的抗病毒治疗与乙肝病毒基因变异情况。方法317例HBV相关终末期肝病患者肝移植术后15例单独使用LAM，302例使用小剂量乙肝免疫球蛋白（hepatitis B immune globulin，HBIG）和拉米夫定（lamivudine，LAM）（或adefovir dipivoxil，ADV）联合预防HBV再感染，同时检测HBV血清标志物、血清HBV DNA、YMDD区变异、及肝活检组织乙型肝炎标记物。结果术后LAM组有4例术前HBV DNA阳性患者术后HBV再感染，LAM＋HBIG联合用药组16例HBV再感染，两组术后HBV再感染差异有统计学意义（26．7％VS．5．30％，P〈0．01）。317例患者术后12例发生YMDD变异，发生率为3．79％，再感染病例60％（12／20）。经加用ADV治疗后5例HBV DNA转阴性，4名患者HBV DNA滴度下降，肝功能显著改善，3例发生纤维淤胆性肝炎，2例死亡，1例经再次肝移植治愈。结论小剂量HBIG＋LAM可以有效地预防肝移植术后HBV再感染；在小剂量HBIG＋LAM用药基础上HBV再感染可能产生YMDD（tyrosine，methionine，aspartate，aspartate）变异；ADV可作为LAM耐药后用药，对于发生突破性感染的患者应采取以ADV为主的综合治疗。     

Strong association between IgA nephropathy and hepatitis B surface antigenemia in endemic areas

The frequency of hepatitis B surface antigen (HBsAg) was studied in the sera of 122 patients with primary IgA nephropathy. Hepatitis B surface (HBs) antigenemia was detected in 21 patients (17.2%) and this was significantly higher than the prevalence of HBsAg carrier in the general population (p less than 0.01). These patients had no clinical or laboratory findings to suggest acute or chronic liver diseases. Two glomerulopathic entities: mesangial proliferative glomerulonephritis with predominant mesangial IgA deposits and a mixed picture of membranous nephropathy with capillary IgG deposits and mesangial proliferative glomerulonephritis with mesangial IgA deposits, were observed in this group of patients. Glomerular deposits of HBsAg, hepatitis B core antigen (HBcAg), and both HBsAg and HBcAg were detected in three, five and four renal biopsy specimens respectively. Replication of hepatitis B virus (HBV) was suggested in two of the six renal biopsy specimens examined by HBV DNA gene probe. During the mean study period of 40 months (range 12-84), 19% of these patients with hepatitis B virus-associated IgA nephropathy developed progressive renal deterioration and one required maintenance dialysis therapy. Our study suggests that hepatitis B virus antigenemia may play a significant pathogenetic role in the development of IgA nephropathy in areas of high HBV endemicity and these HBV-associated IgA nephropathies can run an indolent but relentless slowly progressive clinical course.     

The increased risk of fatal liver disease in renal transplant patients who are hepatitis Be antigen and/or HBV DNA positive

To determine whether active viral replication is associated with increased morbidity and mortality in chronic carriers of hepatitis B virus (HBV) undergoing renal transplantation, we reviewed 23 years of experience at our hospital. Over the period 1966-1989, 42 chronic carriers of hepatitis B surface antigen (HBsAg) received renal transplants, 32 of whom had functioning grafts for 12 months or longer. Stored sera were tested for markers of hepatitis B virus, hepatitis C virus (HCV), and hepatitis delta virus (HDV) infection, and the serologic findings were correlated with clinical and biochemical data. The presence of HBV DNA and/or hepatitis Be antigen (HBeAg) in serum samples collected prior to transplantation was associated with an increased probability of death from liver disease. Whereas 5 of 10 patients in this group died of chronic liver disease, only 1 of 15 patients who were HBV DNA and/or HBeAg negative prior to transplantation died of liver disease. This difference is highly significant (P less than 0.02). No difference in outcome was attributable to age at transplantation, gender, country of birth, or the presence of abnormal hepatic transaminase levels prior to transplantation.     

Membranous glomerulonephritis associated with hepatitis B antigen in children: a comparison with idiopathic membranous glomerulonephritis

The laboratory and pathological findings are reported for 16 children with membranous glomerulonephritis (MGN) associated with hepatitis B virus (HBV) infection and compared with those of 12 children with idiopathic MGN. Serum hepatitis B surface antigen (HBsAg) was found in all children with HBV associated MGN and serum hepatitis B e antigen (HBeAg) in 11 of the 15 examined. Five patients with HBV associated MGN, but none with idiopathic MGN, showed reduced serum C3 values. Otherwise there was no difference in laboratory findings. HBeAg was detected in the glomeruli of all 7 patients with HBV-associated MGN examined but HBsAg was not detected. Of the 14 children with HBV-associated MGN examined by electron microscopy, all but one showed small mesangial deposits and 4 subendothelial deposits, whereas of 9 with idiopathic MGN only 2 showed mesangial deposits and none subendothelial deposits. Thus most of the children with HBV-associated MGN are characterized by some laboratory and pathological features of membrano proliferative glomerulonephritis in addition to those of idiopathic MGN. These observations are consistent with HBV inducing a spectrum of glomerulopathy from typical MGN to typical membranoproliferative glomerulonephritis.     

霉酚酸对乙型肝炎病毒作用的体外实验

目的 探讨霉酚酸(MPA)在体外对乙型肝炎病毒(HBV)基因复制、病毒蛋白合成的影响。方法 将不同浓度的MPA(1～50nag／L)作用于2．2．15细胞，12d后用酶联免疫吸附试验检测培养上清液中乙型肝炎表面抗原(HBsAg)和e抗原(HBeAg)，狭缝印迹杂交法定量分析培养细胞内的HBV DNA。结果 霉酚酸对HV的复制起轻微的抑制作用，随着浓度的增加，抑制作用逐渐增强；50mg／L的MPA对HBsAg、HBeAg的抑制率分别为24．05％和30．20％，HBV DNA的表达量仅为对照组的49％。结论 霉酚酸具有抑制2．2．15细胞分泌HBsAg、HBeAg和复制HBV DNA的作用，并呈剂量依赖性。