儿童血清学阴性乙型肝炎病毒相关性肾炎13例临床与病理分析

目的 回顾性分析儿童血清学阴性乙型肝炎病毒相关性肾炎（sn HBV-GN）的临床及病理学特征，并初步探讨免疫抑制剂治疗的安全性和有效性。方法 收集 2006 年 1 月至 2011年12月经首都医科大学附属北京儿童医院肾活检诊断为HBV-GN病例，根据血清学结果筛选出HBsAg和HBV-DNA阴性患儿，分析其临床、病理资料和治疗情况。结果 13例sn HBV-GN患儿进入分析，男8例，女5例，平均年龄11.8岁。临床表现以肾病综合征为主（11例），9例伴有血尿；2例表现为肾炎综合征。①11例以不典型膜性肾病为主要病理表现，免疫荧光以IgG、C3沉积为主， 亦可见IgA、IgM、C1q沉积。②肾组织HBsAg与HBcAg阳性率分别为100%（13/13）和76.9%（10/13），强阳性率分别为23.1%（3/13）和15.4%（2/13）。③2例肾炎综合征患儿经抗凝和卡托普利治疗完全缓解；11例肾病综合征患儿，单纯抗病毒治疗2例均未缓解；单纯糖皮质激素治疗2/3例部分缓解，糖皮质激素加环孢素治疗2/3例部分缓解，糖皮质激素加用麦考酚酸酯治疗3例均完全缓解。加用免疫抑制剂患儿均未发现肝功能异常及HBV-DNA活动表现。结论儿童sn HBV-GN的病理以不典型膜性肾病为主要表现；免疫荧光显示免疫复合物的种类少，沉积强度低；麦考酚酸酯联合激素治疗较单用激素或激素联合环孢素治疗可能有效，单纯抗病毒治疗可能无效。

The study of clinical and pathological features of seronegative hepatitis B virus-associated glomerulonephritis in 13 children

Objective This study performed a retrospective analysis of clinical and pathological features of seronegative hepatitis B virus-associated glomerulonephritis (sn HBV-GN) to explore the safety and efficacy of immunosuppressant treatment. Methods The patients who had been diagnosed with HBV-GN and serum markers was negative (HBsAg and HBV-DNA) in Beijing Children's Hospital from January 2006 to December 2011 were recruited out. Then the clinical and pathological features were analyzed and followed-up. Results Among 13 patients diagnosed as sn HBV-GN, the ratio of male to female was 1.6∶1, with a mean age at onset of 11.8 years. Nephrotic syndrome was the most common clinical manifestation (11/13), the other two patients (2/13) were with nephritis syndrome. The pathological feature of most patients had atypical membranous nephropathy (11/13, 84.6%) as shown by light microscopy. Immunofluorescence staining most commonly showed IgG and C3, IgA, IgM and C1q deposition was also seen. The HBsAg and HBcAg positive rates were 100% and 76.9%, respectively. The strong positive rate was 23.1% and 15.4%, respectively. Two patients with nephritis syndrome were complete remission. Among the 11 patients with nephritic syndrome, 2 patients treated with antivirus were non-remission; 2 of 3 patients with predinsone were partial remission; 2 of 3 patients with prednisone combined with CsA were partial remission; 3 patients were complete remission, whose therapeutic schedule was prednisone combined mycophenolate mofetil. None of the patients with immunosuppressive agents showed evidence of HBV activity. Conclusion Atypical membranous nephropathy was the most common pathological feature in children with sn HBV-GN. The intensity and type of deposition in immunofluorescence of sn HBV-GN were low. Prednisone combined mycophenolate mofetil was more effective than single prednisone and prednisone combined Cyclosporine A, single antiviral treatment may be ineffective. Results: (1). Among the 13 patients, male:female=1.6:1, with a mean age at onset of 11.85 years, during Adolescence. (2).Clinical feature: Nephrotic syndrome was the most common clinical manifestation (11/13), the other two patients (2/13) was nephritis syndrome. (3). Pathological feature: Most patients had atypical membranous nephropathy (11/13, 84.6%) as shown by light microscopy. Immunofluorescence staining most commonly showed with IgG and C3, IgA、IgM and C1q deposition were also seen. Only IgG existed strong positive deposition. The HBsAg and HBcAg positive rate were 100% and 76.9%, respectively. And the strong positive rate were 21.7% and 13.6% , respectively. (4).Two patients (2/2) with nephritis syndrome were complete remission. Three patient (3/11) in nephritic syndrome were complete remission, whose therapeutic schedule was prednisone combined mycophenolate mofetil. (5) None of the patients with immunosuppressive agents showed evidence of HBV activity. Conclusions: (1) In children, atypical membranous nephropathy was the most common pathological feature in children with sn HBV-GN, which was hard to distinguish from idiopathic membranous nephropathy. So we suggested to perform HBV antigen test in renal to avoid missed diagnosis. (2) The intensity and type of deposition in immunofluorescence of sn HBV-GN were different from seropositive HBV-GN whose deposition was “all bright”. (3) Immunosuppressive agents were safe to use in sn HBV-GN patients. Patients with normal liver function and no evidence of HBV activity do not require antiviral treatment, but liver function and HBV serum markers should be regularly examined. (4) Prednisone combined mycophenolate mofetil was more effective than single prednisone and prednisone combined Cyclosporine A, single antiviral treatment was ineffective.