Department of Nephrology, General Hospital of Chinese PLA, Beijing 100853, China.
World J Gastroenterol. 2012 Feb 28;18(8):821-32. doi: 10.3748/wjg.v18.i8.821.
To investigate the efficacy and safety of combined antiviral and immunosuppressant therapy in adult hepatitis B virus-associated glomerulonephritis (HBV-GN) patients.
A computerized literature search was carried out in the PubMed database, Embase, the Cochrane Library, Chinese BioMedical Literature on disc, Chinese Medical Current Contents, Chinese National Knowledge Infrastructure, Wanfang and VIP (Chinese Technological Journal of Database) to collect articles between June 1980 and December 2010 on therapy with immunosuppressants, e.g., glucorticosteroids, mycophenolate mofetil and leflunomide, combined with antivirals, e.g., interferon, lamivudine, entecavir and adefovir dipivoxil, in adult HBV-GN patients. The primary outcomes were remission of proteinuria, clearance of HBV e-antigen, and elevation of serum albumin. The secondary outcomes were blood levels of alanine aminotransferase, serum creatinine, and HBV-DNA titer. Meta-analysis was performed using Review Manager 5.1. Fixed or random effect models were employed to combine the results after a heterogeneity test. The effects of the combined therapy were analyzed for different doses of glucorticosteroid and different types of HBV-GN.
Twelve clinical trials with 317 patients were included. A significantly higher incidence of HBV-GN was found in male patients (relative risk = 2.40, 95% CI: 1.98-2.93). Combined therapy reduced the proteinuria significantly with a mean difference of 4.19 (95% CI: 3.86-4.53) and increased the serum albumin concentration significantly with a mean difference of -11.95 (95% CI: -12.97-10.93) without significant alterations of liver function (mean difference: 4.62, 95% CI: -2.55-11.79) and renal function (mean difference: 10.29, 95% CI: 0.14-20.45). No significant activation of HBV-DNA replication occurred (mean difference: 0.12, 95% CI: -0.37-0.62). There was no significant difference between the high dose glucorticosteroid group and the low dose glucorticosteroid group in terms of proteinuria remission (P = 0.76) and between different pathological types of HBV-GN [membranous glomerulonephritis (MN) vs. mesangial proliferative glomerulonephritis, P = 0.68; MN vs membranoproliferative glomerulonephritis, P = 0.27].
Combined antiviral and immunosuppressant therapy can improve the proteinuria in HBV-GN patients without altering HBV replication or damaging liver and renal functions.
观察抗病毒联合免疫抑制剂治疗乙型肝炎病毒相关性肾小球肾炎(HBV-GN)的疗效及安全性。
计算机检索 1980 年 6 月至 2010 年 12 月PubMed 数据库、Embase 数据库、Cochrane 图书馆、中国生物医学文献数据库、中国期刊全文数据库、中国生物医学文献服务系统、万方数据资源系统和中文科技期刊数据库(维普数据库),收集抗病毒联合免疫抑制剂治疗 HBV-GN 的文献,包括糖皮质激素、霉酚酸酯、来氟米特联合干扰素、拉米夫定、恩替卡韦、阿德福韦酯等。主要疗效终点为蛋白尿缓解、HBV e 抗原清除、血清白蛋白升高。次要疗效终点为丙氨酸氨基转移酶、血肌酐、HBV-DNA 载量。采用 RevMan 5.1 软件进行 Meta 分析。异质性检验后采用固定或随机效应模型进行合并。分析不同剂量糖皮质激素和不同病理类型 HBV-GN 患者的治疗效果。
共纳入 12 项临床试验,317 例患者。结果显示,男性 HBV-GN 发生率显著高于女性(相对危险度=2.40,95%CI:1.98~2.93)。联合治疗能显著降低蛋白尿,平均差值为 4.19(95%CI:3.86~4.53),显著升高血清白蛋白水平,平均差值为-11.95(95%CI:-12.97~10.93),对肝功能(平均差值:4.62,95%CI:-2.55~11.79)和肾功能(平均差值:10.29,95%CI:0.14~20.45)无明显影响,对 HBV-DNA 复制无明显激活作用(平均差值:0.12,95%CI:-0.37~0.62)。高剂量糖皮质激素组和低剂量糖皮质激素组在蛋白尿缓解方面差异无统计学意义(P=0.76),不同病理类型 HBV-GN 之间差异亦无统计学意义[膜性肾小球肾炎(MN)与系膜增生性肾小球肾炎比较,P=0.68;MN 与膜增殖性肾小球肾炎比较,P=0.27]。
抗病毒联合免疫抑制剂治疗能改善 HBV-GN 患者的蛋白尿,不改变 HBV 复制,对肝功能和肾功能无损害。