IgA nephropathy and hepatitis B virus. IgA nephropathy unrelated to hepatitis B surface antigenemia

The incidence and pathogenetic role of hepatitis B surface antigen (HBsAg) were evaluated in patients with IgA nephropathy. Among 130 consecutive patients with IgA nephropathy, HBs antigenemia was detected in 4 patients (3.1%). Serum antibody to hepatitis B core antigen was positive in these 4 patients indicating that they were persistent carriers of hepatitis B virus. Serum hepatitis B e antigen (HBeAg) was detected in 1 patient, and antibody to HBeAg was positive in the other 3 patients. The incidence of HBs antigenemia was not significantly higher than the 2.0% of the general population. An immunofluorescent study in the renal tissues from the 4 IgA-nephritic patients with HBs antigenemia did not demonstrate HBsAg or HBeAg in the glomeruli. These findings suggest that HBsAg appears to play no role in the pathogenesis of IgA nephropathy.     

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.     

膜性乙型肝炎病毒相关性肾炎与特发性膜性肾病临床对比分析

目的：探讨膜性乙型肝炎病毒相关肾炎（HBV-MN）的临床、病理特点及中医证候特征。方法：采用回顾性分析方法,比较27例HBV-MN和31例特发性膜性肾病（IMN）临床表现、肾脏病理及中医证候等方面的异同。结果：（1）临床表现：HBV-MN组发病年龄明显低于IMN组（P〈0.05）;两组临床表现构成比经Fisher精确卡方检验具有统计学差异（P〈0.05）。（2）肾脏病理：两组均以Ⅰ期、Ⅱ期膜性肾病常见,肾脏病理分期无统计学差异（P〉0.05）;光镜检查,两组肾小球、肾小管间质及肾血管等各项病理积分无统计学差异（P〉0.05）;免疫荧光检查,HBV-MN组表现为多种免疫复合物、多部位、高强度沉积,而IMN组主要以IgG、C3在上皮下和基底膜高强度沉积。（3）中医证候：本虚证中,两组均以脾肾气虚所占比例最高,而且两组本虚证候分布及各项本虚证候积分均无统计学差异（P〉0.05）;标实证中,HBV-MN组湿热证所占比例明显高于IMN组（P〈0.05）,而IMN组中血瘀证和水气证所占比例明显高于HBV-MN组（P〈0.05）。HBV-MN组湿热证候积分明显大于IMN组（P〈0.05）,而IMN组血瘀证候积分明显大于HBV-MN组（P〈0.01）。结论：HBV-MN多发于男性中、青年,主要临床表现为肾病综合征、慢性肾炎综合征合并肾病综合征;病理特征为多种免疫复合物、多部位、高强度沉积,以Ⅰ期、Ⅱ期膜性肾病常见;中医证候以脾肾气虚挟湿热为主。     

小儿肾病患者肾组织病毒基因表达及临床意义

目的：探讨病毒感染在小儿肾脏病发病中的致病作用及临床意义。方法：应用聚合酶链反应（PCR）检测了224例小儿肾病患血清及肾活检组织中乙型肝炎病毒（HBV）、丙型肝炎病毒（HCV）、EB病毒（EBV）和巨细胞病毒（CMV）基因表达情况。结果：小儿肾病患血清和肾组织中HVB DNA检出阳性率分别为21.4%和19.6%;HCVRNA阳性率为4.0%和3.1%;EBVDNA阳性率为1.8%和0.5%;CMV DNA阳性率为0.9%和0.5%。结论：HBV感染在小儿肾脏疾病发病因素上起着重要的作用,HCV感染与小儿肾病的关系尚不明确,而EBV和CMV感染导致小儿肾病比较罕见。     

Membranous nephropathy in an HIV-positive patient complicated with hepatitis B virus infection

In ordinary settings, human immunodeficiency virus (HIV)-associated nephropathy should be considered when HIV infection is associated with heavy proteinuria. On the other hand, hepatitis B virus (HBV) may also play a role in the development of glomerular injury among patients with HIV infection, since HIV and HBV infections commonly occur together due to shared modes of transmission. We present here a case of nephrotic syndrome in an HIV-positive patient complicated with HBV infection. A renal biopsy revealed sparse granular deposits of immunoglobulin G in the subepithelial region, consistent with membranous nephropathy (MN) stage I. Moreover, immunostaining exhibited weak anti-hepatitis B core activity within glomeruli. These results led us to consider that HBV-associated MN might play a role in the development of nephrotic syndrome. Although anti-viral treatment for patients with HBV-associated MN has been suggested to be clinically effective, the use of two anti-HIV agents (tenofovir and emtricitabine), both of which have anti-HBV activities, was not effective for the patient's nephrotic syndrome, despite obtaining a decrease in the serum HBV-DNA levels. A lack of prospective data suggests that many decisions on the treatment of glomerulopathies with HIV infections are potentially empirical. Obviously, further studies and accumulated clinical experience are required to better determine the pathogenesis and management of HBV-associated MN among patients with HIV infections.     

The clinical course of hepatitis B virus-associated nephropathy

Hepatitis B virus (HBV) infection is recognised as an important cause of nephrotic syndrome in endemic areas. This paper retrospectively examines the natural history and treatment of 70 patients with membranous glomerulonephritis and 1 with mesangiocapillary glomerulonephritis associated with HBV infection. Thirty-seven patients were in complete remission by the end of the study. The average duration of proteinuria in these patients was 30 months. The cumulative probability of remission was 64% at 4 years and 84% at 10 years. Three patients were still nephrotic after more than 90 months of follow-up and 2 others had reached end-stage renal failure. Remission occurred within 6 months of clearing the e antigen (HBeAg) in the majority of cases. Steroids alone were given to 10 patients and 2 received steroids and cyclophosphamide, with no beneficial effect. Three patients received interferon- 2b. One cleared the HBeAg from the circulation and had a significant fall in proteinuria, but defaulted from follow-up a month after completing treatment. One had a reduction of proteinuria but remained HBeAg positive. There was no change in the condition of the third. Although the majority of children eventually enter remission, there is a significant morbidity associated with the disease. Steroids and other immunosuppressive therapy are of no benefit. Interferon therapy may be useful, but has not been adequately assessed.     

IgA nephropathy in Japanese children and adults: a comparative study of clinico-pathological features

A comparative clinico-pathological study was performed on 61 children and 51 adults with IgA nephropathy. Hematuria and/or proteinuria found by chance was the most common initial clinical sign, being observed in 82.0% of the children and 52.9% of the adults (p less than 0.001). At renal biopsy, hypertension and severe proteinuria were found in 9.8% and 33.3% of the adults and 0 and 14.8% of the children (p less than 0.05, p less than 0.05). Elevations of blood urea nitrogen and serum creatinine were found at the time of biopsy in 21.6% and 9.8% of the adults but in none of the children (p less than 0.001, p less than 0.05). On histological studies, proliferative changes of the glomerulus were similar in the two groups, and diffuse mesangial proliferation was found in 62.3% of the children and 51.0% of the adults (although the difference was not significant). Focal glomerulosclerosis and tubular atrophy were found in 52.9% of the adults and 32.8% of the children (p less than 0.05). These results suggest that focal glomerulosclerosis with tubular atrophy is correlated with deterioration of renal function, hypertension and age at renal biopsy, and has an important influence on the prognosis of patients with IgA nephropathy.     

乙型肝炎病毒X基因诱导卵圆细胞恶性转化的研究

目的 研究乙型肝炎病毒X(HBx)基因对卵圆细胞转化和分化的影响.方法 用稳定表达HBx的转基因即圆细胞株pEGFP-HBx卵圆细胞作为实验组,pEGFP卵圆细胞及LE/6卵圆细胞作为对照组,运用倒置相差显微镜和透射电镜、流式细胞术、糖原染色、软琼脂生长、实时定量PCR、细胞免疫化学技术观察和检测pEGFP-HBx卵圆细胞在细胞形态、细胞周期、分化标志物、癌基因c-myc及TGF-α的变化.结果 (1)与对照组相比,pEGFP-HBx卵圆细胞体积增大,核具有明显异型性;(2)流式细胞仪检测显示,与对照组相比,pEGFP-HBx卵圆细胞G0/G1期细胞百分比下降,S期和G2/M期细胞百分比明显升高,而且非整倍体细胞明显增多;(3)糖原染色显示,pEGFP-HBx卵圆细胞胞质内可见大量糖原颗粒;(4)软琼脂中可见pEGFP-HBx卵圆细胞克隆形成;(5)癌基因c-myc及TGF-α表达量明显增高,卵圆细胞分化指标HNF-4α、AFP表达上升,CK-7、CK-19表达下降,未见有cps1 mRNA表达.结论 HBx基因可以引起卵圆细胞异常分化,并直接诱导卵圆细胞发生恶性转化.     

The extrahepatic manifestations of hepatitis B virus

Hepatitis B Virus (HBV) leads to a number of hepatic complications, from acute to chronic hepatitis, cirrhosis and hepatocellular carcinoma, is a well-established fact. Upcoming clinical research, over the years, associates numerous extrahepatic manifestations during the acute and chronic episodes of hepatitis B with significant morbidity and mortality. A causal relationship between HBV and serious autoimmune disorders has also been observed among certain susceptible vaccine recipients in a defined temporal period following immunization. The cause of these extrahepatic manifestations is generally believed to be immune mediated. The most commonly described include skin rash, arthritis, arthralgia, glomerulonephritis, polyarteritis nodosa, and papular acrodermatitis etc. The serum-sickness like "arthritis-dermatitis" prodrome has also been observed in approximately one-third of patients acquiring HBV infections. Skin manifestations of HBV infection typically present as palpable purpura reported to be caused by chronic HBV, although this association remains controversial. To consider the relationship between HBV and other clinically significant disorders as well as serious autoimmune disorders among certain vaccine recipients is the topic of this review. Variable factors that influence extrahepatic manifestation are discussed, including possible synergy between hepatitis B virus and the immune system.     

Biochemical and serological characteristics of children with membranous nephropathy due to hepatitis B virus infection: correlation with hepatitis B e antigen, hepatitis B DNA and hepatitis D

Fourteen children with biopsy-proven membranous nephropathy associated with hepatitis B virus (HBV-MN) were evaluated biochemically and serologically and compared to 45 children with idiopathic nephrotic syndrome (INS). The mean ages of the two groups were similar (4.9 +/- 1.6 vs. 4.6 +/- 2.6 years). Serum albumin levels were similar in both groups, but serum cholesterol was significantly reduced in children with HBV-MN compared to INS. Serum C3 was also significantly depressed in children with HBV-MN compared to INS, but no differences in C4 levels were noted. Serum alanine transaminase as well as aspartate transaminase concentrations were significantly elevated in children with HBV-MN compared to those with INS, suggesting the presence of chronic hepatitis in children with HBV-MN. Hepatitis B surface and e antigens were present in serum of all children with HBV-MN, but only 54% had circulating HBV-DNA particles demonstrable in their serum. Serum C3 levels were higher in children with HBV-MN and circulating HBV-DNA, compared to those without circulating HBV-DNA. No other serological or biochemical differences occurred between these two groups. Glomerular deposition of IgG and C3 occurred in 91% of children with HBV-MN; but IgM deposition appeared to occur more frequently and with greater intensity in those children positive for circulating HBV-DNA. Antibody to delta antigen was negative in all children with HBV-MN. We conclude that biochemical and serological differences can be identified between HBV-MN and INS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of hepatitis B virus-associated nephropathy in black children

The efficacy of interferon (IFN) in the treatment of hepatitis B virus (HBV)-associated nephropathy in black children has not been established. Twenty-four black children with biopsy-proven HBV-associated nephropathy were recruited into the study during the period April 1997 to June 1999. Five defaulted treatment and were excluded from the primary analysis. IFNalpha 2b was administered for 16 weeks. Response to treatment was defined as loss of HBeAg, decrease in proteinuria, and prevention of deterioration in renal and liver function. A control group of 20 patients was followed up for the same period. Ten (52.6%) of the treated children responded with clearance of HBeAg by 40 weeks. None cleared HBsAg. All responders showed remission of proteinuria, 90% maintained normal renal function and 1 (10%) showed improvement of renal function. HBV DNA levels decreased in this group. Nine patients did not clear HBeAg; none showed remission of proteinuria, and two showed deterioration of renal function. Liver enzymes rose during treatment but subsequently declined irrespective of response to therapy. No serious side effects were encountered. Only 5% of controls showed spontaneous clearance of HBeAg, and none had remission of proteinuria. Black children with HBV-associated nephropathy show accelerated clearance of HBeAg with remission of proteinuria following treatment with IFNalpha 2b. IFNalpha 2b was well tolerated.     

Membranous nephropathy following perinatal transmission of hepatitis B virus infection—a long-term follow-up study

In children with hepatitis B-associated membranous glomerulonephritis, the time of onset of the infection and the duration of the carrier state before diagnosis of the renal disease are always unknown. Moreover, followup is usually short. We report the unique observation of a French girl who was infected with hepatitis B virus by her mother who had acute hepatitis during the immediate postpartum period; the girl developed proteinuria at 6 years of age. The onset of the infection in the perinatal period, the mild liver abnormalities, and the absence of nephrotic syndrome did not justify any treatment. Spontaneous seroconversion to anti-HBe antibody positive occurred at 12 years of age. Proteinuria gradually diminished and was absent at 18 years. However, HBs antigenemia persits.     

The therapeutic dilemma of the usage of corticosteroid in patients with membranous nephropathy and persistent hepatitis B virus surface antigenaemia

The therapeutic benefits and risks of short-term corticosteroid were investigated in 8 patients with membranous nephropathy and hepatitis B surface antigenaemia. Seven patients presented with nephrotic syndrome, and the remaining patient had significant proteinuria. Their liver function tests were normal on repeated examination. Their sera demonstrated the persistent presence of hepatitis B virus surface antigen and high titres of antibody to hepatitis B virus core antigen. Hepatitis B virus e antigens were present in the sera of 4 patients at initial presentation. Their clinical responses were compared with 7 similar patients previously treated with diuretic therapy alone and acting as historic controls. Short-term corticosteroid (6 months) with stepwise reduction resulted in an early regression of the nephrotic syndrome in 3 patients. Five patients had persistent but reduced proteinuria. Transient liver impairment was observed in 3 patients. Corticosteroid therapy induced transient viral replication with increased serum concentration of hepatitis B virus e antigen and hepatitis B virus DNA. Two of the 7 patients receiving diuretics developed spontaneous remission though apparently later than those receiving corticosteroid. Yet complications such as liver dysfunction and hypertension were not observed in the patients treated with diuretics. Our findings suggest that corticosteroid therapy could be harmful in membranous nephropathy related to hepatitis B surface antigenaemia, as activation of viral replication could occur with corticosteroid therapy.     

Membranous nephropathy associated with hepatitis B in Spanish children

AIM: To examine retrospectively long-term evolution and treatment of pediatric membranous nephropathy (MN) cases associated with hepatitis B (HB) in the hospital "La Paz". MATERIAL AND METHODS: The clinical records of 12 children diagnosed with HB-associated MN in our hospital between 1970 and 1996. RESULTS: All patients were positive for hepatitis B surface antigen (HBsAg); 6 were tested for hepatitis Be antigen (HBeAg) and were also positive. At onset, all of them had proteinuria (8 in nephrotic range), 6 had microscopic hematuria and 4 macroscopic hematuria. Seven of 8 children who started with a nephrotic syndrome received steroids and all of them were steroid-resistant. After 9.95 +/- 5.88 years of follow-up, renal function remained normal and proteinuria and hematuria have disappeared in all of them. A family study for hepatitis B was carried out in 8 cases and 7 of them were positive. Only in one case vertical transmission was demonstrated; this patient remained HBeAg positive. In 7 patients, hepatic biopsy was performed: 3 had a chronic active hepatitis, 3 a persistent chronic hepatitis and one a residual acute hepatitis. CONCLUSIONS: Membranous nephropathy is a rare pediatric disease in our area and most of the cases are related to hepatitis B (HB). The outcome was excellent with and without treatment but all of them remained HBsAg positive.     

Effect of interferon therapy on hepatitis B virus related membranous nephropathy associated with focal segmental glomerulosclerosis

We experienced a 24-year-old Japanese man, who was a hepatitis B virus carrier with nephrotic syndrome. Liver biopsy showed that he was suffering from chronic hepatitis (activity 2, fibrosis 2). Renal biopsy revealed membranous nephropathy(MN) with focal segmental glomerulosclerosis(FGS). Immunofluorescentic findings revealed the presence of HBe antigen along the glomerular capillaries as well as HBe antigenemia in circulation. Therefore, we diagnosed this case as HB virus-related membranous nephropathy associated with FGS lesions. He was treated with interferon(IFN) alpha-2b for over a month and angiotensin converting enzyme inhibitor. These therapies reduced urinary protein excretion from 4-6 g/day to 1-2 g/day, in accordance with a decrease in the titer of HBV DNA polymerase. The second renal biopsy revealed that the histological change from MN to membranoproliferative glomerulonephritis Type III after IFN therapy. These results suggest that IFN therapy might be effective for HB virus-related MN associated with FGS.     

慢性乙型肝炎患者病毒准种的研究进展

由于乙型肝炎病毒（HBV）的逆转录酶缺乏校正活性,在病毒复制过程中产生大量核苷酸错配,故HBV在宿主体内表现为大量在遗传学上高度相关而又有差别的病毒群体,这一群体称为准种,宿主体内的病毒准种在宿主免疫压力和药物的选择压力下不断发生动态变化,因此HBV准种变化在慢性乙型肝炎的抗病毒治疗、耐药检测以及预后等方面均有重要作用。本文对HBV准种变化与慢性乙型肝炎进展的关系作一综述。