对拉米夫定治疗无应答或变异的乙型肝炎病毒相关性肾炎的治疗

Treatment of HBV associated glomerulonephritis refractory or with variation response to lamivudine

目的探讨对拉米夫定治疗无应答或变异的乙型肝炎病毒相关性肾炎(HBV-GN)的治疗方法。方法 2005年1月至2009年1月南京军区福州总医院诊治的HBV-GN且对拉米夫定治疗无应答或变异的患者共9例。采用恩替卡韦(0.5 mg/d)为主方案治疗9例对拉米夫定治疗无应答或变异的HBV-GN且蛋白尿>1.5 g/d、血HBV-DNA≥1.0×108拷贝/L的患者,观察其疗效及血HBV-DNA的变化。结果 9例患者肾病综合征(NS)7例、蛋白尿伴血尿2例,其中系膜增生性肾炎3例,膜性肾病3例,膜增生性肾炎、IgA肾病及局灶节段系膜增生性肾炎各1例。拉米夫定治疗(14.1±10.3)个月(其中6例联合激素治疗),5例部分缓解(PR)、4例无效(均为NS),改用恩替卡韦治疗后,治疗12个月时7例完全缓解(CR)、1例PR、1例NR,7例检测血清HBV-DNA水平患者中5例降至正常,随访观察了19～27个月,平均(23.7±3.0)个月,至随访结束,完全缓解(CR)7例,NR 2例,均停用激素。未见副反应。结论恩替卡韦为主的治疗对对拉米夫定治疗无应答或变异的HBV-GN是安全有效的,疗程以1年半为宜。

Objective To explore the treatment of HBV associated glomerulonephritis （HBV-GN） refractory or with variation response to lamivudine therapy. Methods Between January 2005 and January 2009,9 cases of HBV-GN refractory or with variation response to lamivudine, were treated in Fuzhou General Hospital of Nanjing Military Region with entecavir （0. 5 mg/d） based therapy. These patients had albuminuria 〉 1.5 g/d and serum HBV-DNA ≥1.0×10^8 copies/mL. The efficacy of entecavir and the change in serum HBV-DNA were then observed. Results Of the 9 cases, nephrotic syndrome （NS） was found in 7 and proteinuria plus microscopic hematuria in 2 cases. Pathologically, these cases included mesangial proliferative GN （n = 3 ）, membranous nephropathy （ n = 3 ）, membranoproliferative nephritis （ n = 1 ）, IgA nephropathy （ n = 1 ） and focal segmental mesangial proliferative nephritis （n = 1 ）. A total of 9 patients were treated with lamivudine for 14. 1 ±10. 3 months. Notably,6 patients were added with corticosteroids. There were 5 cases with partly remission （PR） and 4 cases with no response （all NS）. After treatment with entecavir for 12 months, complete remission were found in 7 cases, PR and NR in 1 case each, respectively. Among 7 patients whose serum HBV-DNA were detected,5 cases had their levels of serum HBV-DNA decreased to normal. After follow-up for 19 to 27 months （mean：23.7 ±3.0 months）, CR was found in 7 cases and NR in 2 cases, all free of steroids. Furthermore, no adverse reaction was found. Conclusion The Entecavir based therapy is safe and effective for treatment of HBV associated glomerulonephritis refractory or with variation response to lamivudine and should be used continuously for one and a half year.