Kataoka Hiroshi, Mochizuki Toshio, Akihisa Taro, Kawasoe Kentaro, Kawachi Keiko, Makabe Shiho, Sawada Anri, Manabe Shun, Sato Masayo, Amemiya Nobuyuki, Mitobe Michihiro, Akanuma Takafumi, Ito Yasuko, Inoue Takahiro, Suzuki Tomo, Matsui Katsuomi, Moriyama Takahito, Horita Shigeru, Ohara Mamiko, Honda Kazuho, Nitta Kosaku
Department of Medicine Kidney Center.
Clinical Research Division for Polycystic Kidney Disease, Department of Medicine, Kidney Center.
Medicine (Baltimore). 2019 Jan;98(2):e14014. doi: 10.1097/MD.0000000000014014.
Adult-onset hepatitis B virus-associated membranoproliferative glomerulonephritis (HBV-MPGN) is generally refractory, and an effective treatment for this condition has not been established. The indications for steroids in HBV-MPGN are an important clinical concern.
A 28-year-old woman with a chronic hepatitis B virus infection developed nephrotic syndrome in her second month of pregnancy, with urinary protein levels of 3 to 10 g/d that continued into her postpartum period. She was a carrier of HBV with HBeAg seroconversion. As her renal impairment could have been a result of pregnancy, we observed her for 10 months postpartum without any intervention. However, spontaneous remission after childbirth was not achieved and urine protein levels were sustained at 1 to 3 g/d. About 10 months after delivery, elevated serum liver enzyme levels were observed.
Biopsies showed MPGN, with deposition of hepatitis B antigen in the glomeruli, and chronic B-type hepatitis with a severity grade of A1F0. She was diagnosed with HBV-MPGN.
The patient was started on entecavir 0.5 mg/d in March 2008. Within 1 month, serum HBV DNA became undetectable; within 3 months, her alanine aminotransferase levels normalized. However, urinary protein excretion did not decrease to <2 g/d. On a second renal biopsy, performed 7 months after entecavir treatment, proliferative lesions of the glomeruli were observed; therefore, prednisolone was started at an initial dose of 30 mg/d.
Her proteinuria improved immediately and prednisolone was tapered over 10 months. A third renal biopsy showed a remarkable resolution of HBV-MPGN, with a significant decrease in mesangial proliferation and immune complex deposition. HBV reactivation was not observed during the prednisolone treatment.
Additional prednisolone therapy in combination with antiviral therapy should be considered for refractory HBV-MPGN, with sufficient care taken regarding HBV reactivation.
成人起病的乙型肝炎病毒相关性膜增生性肾小球肾炎（HBV-MPGN）通常难以治疗，尚未确立针对该病症的有效治疗方法。HBV-MPGN中使用类固醇的指征是一个重要的临床关注点。
一名28岁慢性乙型肝炎病毒感染女性在妊娠第二个月出现肾病综合征，尿蛋白水平为3至10克/天，持续至产后。她是HBV携带者，HBeAg血清学转换。由于其肾功能损害可能是妊娠所致，我们在产后观察了她10个月，未进行任何干预。然而，产后未实现自发缓解，尿蛋白水平维持在1至3克/天。分娩后约10个月，观察到血清肝酶水平升高。
活检显示为膜增生性肾小球肾炎，肾小球中有乙型肝炎抗原沉积，以及严重程度为A1F0的慢性B型肝炎。她被诊断为HBV-MPGN。
患者于2008年3月开始服用恩替卡韦0.5毫克/天。1个月内，血清HBV DNA检测不到；3个月内，她的丙氨酸转氨酶水平恢复正常。然而，尿蛋白排泄未降至<2克/天。在恩替卡韦治疗7个月后进行的第二次肾活检中，观察到肾小球的增殖性病变；因此，开始使用泼尼松龙，初始剂量为30毫克/天。
她的蛋白尿立即改善，泼尼松龙在10个月内逐渐减量。第三次肾活检显示HBV-MPGN明显缓解，系膜增生和免疫复合物沉积显著减少。在泼尼松龙治疗期间未观察到HBV再激活。
对于难治性HBV-MPGN，应考虑联合抗病毒治疗加用泼尼松龙治疗，并充分注意HBV再激活。
