Meta-analysis of combined therapy for adult hepatitis B virus-associated glomerulonephritis

Abstract

Aim: To investigate the efficacy and safety of combined antiviral and immunosuppressant therapy in adult hepatitis B virus-associated glomerulonephritis (HBV-GN) patients.

Methods: 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.

Results: 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].

Conclusion: Combined antiviral and immunosuppressant therapy can improve the proteinuria in HBV-GN patients without altering HBV replication or damaging liver and renal functions.

Keywords: Antiviral drug; Glucocorticoids; Hepatitis B virus-associated glomerulonephritis; Immunosuppressant; Meta-analysis.

Figures

Figure 1

Flowchart showing the abstract screening and study selection process. CBM: Chinese BioMedical Literature on disc; CMCC: Chinese Medical Current Contents; CNKI: Chinese National Knowledge Infrastructure.

Figure 2

Gender difference in trials. M-H: Mantel-Haenszel.

Figure 3

Proteinuria change in steroid combination therapy. IV: Inverse variance.

Figure 4

Serum albumin change in combination therapy group. IV: Inverse variance.

Figure 5

Alanine aminotransferase change in combination therapy group. IV: Inverse variance.

Figure 6

Scr change in combination therapy group. IV: Inverse variance.

Figure 7

Hepatitis B virus-DNA titer change in combination therapy group. IV: Inverse variance.

Figure 8

Proteinuria remission rate in different dose glucorticosteroids subgroups. IV: Inverse variance.

Figure 9

Proteinuria remission rate in membranous glomerulonephritis and mesangial proliferative glomerulonephritis subgroups. M-H: Mantel-Haenszel; MN: Membranous glomerulonephritis; MsPGN: Mesangial proliferative glomemlonephrits; CR: Complete remission; R: Remission.

Figure 10

Proteinuria remission rate in membranous glomerulonephritis and membranoproliferative glomerulonephritis subgroups. M-H: Mantel-Haenszel; MN: Membranous glomerulonephritis; MPGN: Membranoproliferative glomerulonephritis; CR: Complete remission; R: Remission.

Figure 11

Risk of bias graph: Review authors' judgments about each risk of bias item presented as percentages across all included studies.

Figure 12

Risk of bias graph: Review authors' judgments about each risk of bias item for each included study.

Figure 13

Publication bias analysis. A: Funnel plots of proteinuria treatment with steroid combination therapy; B: Funnel plots of serum albumin change with steroid combination therapy; C: Funnel plots of proteinuria change under different combined glucorticosteroids drugs; D: Funnel plots of remission rate vs complete remission rate of MN and MsPGN groups; E: Funnel plots of remission rate vs complete remission rate of MN and MsPGN groups. MN: Membranous glomerulonephritis; MsPGN: Mesangial proliferative glomemlonephrits; R: Remission; CR: Complete remission; RR: Relative risk; MD: Mean difference.