Efficacy and safety of anti-viral therapy for Hepatitis B virus-associated glomerulonephritis: A meta-analysis

Autoři: Baohui Fu aff001;  Yue Ji aff001;  Shouci Hu aff002;  Tong Ren aff001;  Maheshkumar Satishkumar Bhuva aff003;  Ge Li aff004;  Hongtao Yang aff001
Působiště autorů: Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China aff001;  The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Zhejiang, China aff002;  International Department, Tongji University School of Medicine Affiliated Shanghai Pulmonary Hospital, Shanghai, China aff003;  Public Health Science and Engineering College, Tianjin University of Traditional Chinese Medicine, Tianjin, China aff004
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227532



To assess the potency of anti-viral treatment for hepatitis B virus-associated glomerulonephritis (HBV-GN). Method: We searched for controlled clinical trials on anti-viral therapy for HBV-GN in MEDLINE, Embase, the Cochrane Library, and PubMed from inception to March 11th 2019. Seven trials, including 182 patients met the criteria for evaluating. The primary outcome measures were proteinuria and changes in the estimated glomerular filtration rate, and the secondary outcome measure was hepatitis B e-antigen clearance. A fixed or random effect model was established to analyze the data. Subgroup analyses were performed to explore the effects of clinical trial type, anti-viral drug type, age, and follow-up duration.


The total remission rate of proteinuria (OR = 10.48, 95% CI: 4.60−23.89, I2 = 0%), complete remission rate of proteinuria (OR = 11.64, 95% CI: 5.17−26.21, I2 = 23%) and clearance rate of Hepatitis Be Antigen (HBeAg) were significantly higher in the anti-viral treatment group than in the control group (OR = 27.08, 95% CI: 3.71−197.88, I2 = 63%). However, antiviral therapy was not as effective regarding the eGFR (MD = 5.74, 95% CI: -4.24−15.73). In the subgroup analysis, age and drug type had significant impacts on proteinuria remission, and study type and follow-up duration only slightly affected the heterogeneity.


Antiviral therapy induced remission of proteinuria and increased HBeAg clearance but failed to improve the eGFR. Pediatric patients were more sensitive to antiviral therapy than adults. IFNs seem more effective but are accompanied by more adverse reactions than NAs.

Klíčová slova:

Adverse reactions – Antiviral therapy – Antivirals – Glomerulonephritis – Hepatitis B virus – Pediatrics – Proteinuria – Randomized controlled trials


1. Collaborators TPO. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018;3(6):383–403. doi: 10.1016/S2468-1253(18)30056-6 29599078

2. Zhang X, Liu S, Tang L, Wu J, Chen P, Yin Z, et al. Analysis of pathological data of renal biopsy at one single center in China from 1987 to 2012. Chin Med J (Engl.). 2014;127(9):1715–1720.

3. Andrassy KM. Comments on'KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease'.Kidney international. 2013;84(3):622–3.

4. Fabrizi F, Dixit V, Martin P. Meta-analysis: anti-viral therapy of hepatitis B virus-associated glomerulonephritis. Alimentary pharmacology & therapeutics. 2006; 24(5):781–788.

5. Khedmat H, Taheri S. Hepatitis B virus-associated nephropathy: an International Data Analysis. Iranian Journal of Kidney Diseases. 2010; 4(2):101. 20404417

6. Zhang Y, Zhou JH, Yin XL, Wang FY. Treatment of hepatitis B virus-associated glomerulonephritis: a meta-analysis. World Journal of Gastroenterology. 2010; 16(6):770–777. doi: 10.3748/wjg.v16.i6.770 20135728

7. Yi Z, Jie YW, Nan Z. The efficacy of anti-viral therapy on hepatitis b virus-associated glomerulonephritis: a systematic review and meta-analysis. Annals of Hepatology. 2011; 10(2):165. 21502678

8. Zheng X Y, Wei R B, Tang L, Li P, Zheng X D. Meta-analysis of combined therapy for adult hepatitis B virus-associated glomerulonephritis. World Journal of Gastroenterology Wjg. 2012; 18(8):821. doi: 10.3748/wjg.v18.i8.821 22371643

9. Wang WN, Wu MY, Ma FZ, Sun T, Xu ZG. Meta-analysis of the efficacy and safety of nucleotide/nucleoside analog monotherapy for hepatitis B virus-associated glomerulonephritis. Clinical Nephrology. 2016; 85(1):21–29. doi: 10.5414/CN108648 26636326

10. Yang Y, Ma Y, Chen DP, Zhuo L, Li WG. A Meta-Analysis of Antiviral Therapy for Hepatitis B Virus-Associated Membranous Nephropathy. Plos One. 2016; 11(9):e0160437. doi: 10.1371/journal.pone.0160437 27598699

11. Higgins J,Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0[updated March 2011].Available:www.cochrane-handbook.org.2011.

12. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions:explanation and elaboration. Bmj. 2009; 339:b2700. doi: 10.1136/bmj.b2700 19622552

13. Editorial board of Chinese Journal of Internal Medicine.Summary of symposium on hepatitis b virus-associated glomerulonephritis. Chin J Intern Med. 1990; 29:518–521.

14. Well G, Shea B, O'Connell D, Peterson J, Welch V, Losos M, et al.The Newcastle-Ottawa Scale(NOS)for assessing the quality of nonrandomised studies in meta-analyses.Available:www.ohri.ca/programs/clinical_epidemiology/oxford.asp. 2014.

15. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ.2003; 327(7414):557–60. doi: 10.1136/bmj.327.7414.557 12958120

16. Dersimonian R, Laird N. Meta-Analysis in Clinical Trials. Controlled Clinical Trials, 1986; 7(3):177–188. doi: 10.1016/0197-2456(86)90046-2 3802833

17. Sun LJ, Shan JP, Cui RL, Yuan WJ, Jiang GR. Combination therapy with lamivudine and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker for hepatitis B virus-associated glomerulonephritis with mild to moderate proteinuria:a clinical review of 38 cases. International Urology and Nephrology. 2017; 49(6):1049–1056. doi: 10.1007/s11255-017-1563-5 28283858

18. Bhimma R, Coovadia HM, Kramvis A, Adhikari M, Kew MC. Treatment of hepatitis B virus-associated nephropathy in black children. Pediatric nephrology. 2002; 17(6):3.

19. Tang S, Lai MM, Lui YH, Tang COS, Kung NNS, Ho YW, et al. Lamivudine in hepatitis B–associated membranous nephropathy. Kidney International. 2005; 68(4):1750–1758. doi: 10.1111/j.1523-1755.2005.00591.x 16164651

20. Panomsak S, Lewsuwan S, Eiamong S, Kanjanabuch T. Hepatitis-B virus-associated nephropathies in adults:a clinical study in Thailand. J Med Assoc Thai. 2006; 89 Suppl 2:S151.

21. Sun IO, Hong YA, Park HS, Choi SR, Choi BS. Experience of Anti-Viral Therapy in Hepatitis B-Associated Membranous Nephropathy, Including Lamivudine-Resistant Strains. Korean Journal of Internal Medicine. 2012; 27(4):411–416. doi: 10.3904/kjim.2012.27.4.411 23269882

22. Au JTC, Lai MD, Lui F, Au TC, Tam JS, Tong KL, et al. Membranous nephropathy related to hepatitis B virus in adults. N Engl J Med. 1991; 324(21):1457. doi: 10.1056/NEJM199105233242103 2023605

23. Lin CY. Treatment of hepatitis B virus-associated membranous nephropathy with recombinant alpha-interferon.Kidney International. 1995; 47(1):225–230. doi: 10.1038/ki.1995.27 7731150

24. Izzedine H, Launay-Vacher V, Deray G. Antiviral Drug-Induced Nephrotoxicity. American Journal of Kidney Diseases. 2005; 45(5):804–817. doi: 10.1053/j.ajkd.2005.02.010 15861345

25. Kara AV, Yıldırım Y, Ozcicek F, Aldemir MN, Arslan Y, Bayan K, et al. Effects of entecavir, tenofovir and telbivudine treatment on renal functions in chronic hepatitis B patients. Acta Gastroenterol Belg. 2019; 82(2):273–277. 31314188

26. Liaw YF. HBeAg seroconversion as an important end point in the treatment of chronic hepatitis B. Hepatol Int. 2009; 3(3):425–33. doi: 10.1007/s12072-009-9140-3 19669245

27. Lok AS, Heathcote EJ, Hoofnagle JH. Management of Hepatitis B 2000, Summary ofa Workshop. Gastroenterology. 2001; 120:1828–1853. doi: 10.1053/gast.2001.24839 11375963

28. Chu CJ, Hussain M, Lok ASF. Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection. Hepatology. 2002; 36(6):1408–1415. doi: 10.1053/jhep.2002.36949 12447866

29. Lai AS, Lai KN. Viral nephropathy. Nature Clinical Practice Nephrology. 2006; 2(5):254–262. doi: 10.1038/ncpneph0166 16932438

30. Lin CY. Hepatitis B Virus-Associated Membraneous Nephropathy: Clinical Features, Immunological Profiles and Outcome. Nephron. 1990; 55(1):37–44. doi: 10.1159/000185916 2191232

31. Ito H, Hattori S, Matsuda I, Amamiya S, Hajikano H, Yoshizawa H, et al. Deposition of hepatitis B e antigen in membranous glomerulonephritis: Identification by F(ab))fragments of monoclonal antibody.Kidney Int. 1984; 26:338–341. doi: 10.1038/ki.1984.178 6513277

32. Takekoshi Y, Tochimaru H, Nagata Y, Itami N. Immunopathogenetic mechanisms of hepatitis B virus-related glomerulopathy.Kidney International Supplement. 1991; 35(35):S34.

33. Bhimma R, Coovadia HM. Hepatitis B Virus-Associated Nephropathy. American Journal of Nephrology. 2004; 24(2):198–211. doi: 10.1159/000077065 14988643

34. Segerer S, Nelson PJ, Ndorff D. Chemokines, chemokine receptors, and renal disease: from basic science to pathophysiologic and therapeutic studies. Journal of the American Society of Nephrology Jasn. 2000; 11(1):152. 10616852

35. Seeger C, Mason WS. Hepatitis B virus biology.Microbiology&Molecular Biology Reviews. 2000; 64(1):51.

36. Ghany M, Liang TJ. Drug Targets and Molecular Mechanisms of Drug Resistance in Chronic Hepatitis B. Gastroenterology. 2007; 132(4):1574–1585. doi: 10.1053/j.gastro.2007.02.039 17408658

37. Pei RJ, Chen XW, Lu M. Control of hepatitis B virus replication by interferons and toll-like receptor signaling pathways. World Journal of Gastroenterology. 2014; 20(33):11618–11629. doi: 10.3748/wjg.v20.i33.11618 25206268

Článek vyšel v časopise


2020 Číslo 1