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Published in: Advances in Therapy 5/2016

Open Access 01-05-2016 | Original Research

Renal Function in Nucleos(t)ide Analog-Treated Patients With Chronic Hepatitis B: A Systematic Literature Review and Network Meta-Analysis

Authors: Henry L. Y. Chan, Javed Shaikh, Subhajit Gupta, Kamal Hamed

Published in: Advances in Therapy | Issue 5/2016

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Abstract

Introduction

Renal safety is an important factor in selecting the most appropriate nucleos(t)ide analog (NA) treatment for patients with chronic hepatitis B (CHB). This systematic literature review and network meta-analysis aimed to assess renal function associated with telbivudine treatment compared to other NAs in patients with CHB.

Methods

A systematic literature search via Medline, Medline In-Process, Embase, and the Cochrane library for publications of randomized controlled trials and observational studies was conducted. Network meta-analysis was performed to compare renal function with telbivudine treatment versus other NAs after 1 year of therapy.

Results

Overall, 40 (six randomized controlled and 34 observational) studies were included for review. Telbivudine consistently showed an improvement in renal function as measured by an estimated glomerular filtration rate (eGFR) over various time points regardless of the method of measurement. Changes in eGFR (mL/min) from baseline and corresponding 95% credible intervals with various NAs were as follows: monotherapies (telbivudine: 7.78 [6.91, 8.65], entecavir: −1.07 [−4.80, 2.62], lamivudine: −6.08 [−13.35, 1.15], tenofovir: −9.53 [−14.31, −4.89]) and combination therapies (telbivudine + adefovir: 8.37 [−34.00, 50.34], telbivudine + tenofovir: 8.29 [−0.05, 16.64], entecavir + adefovir: 4.15 [−38.55, 46.37], telbivudine + lamivudine: 0.51 [−11.77, 12.96], and lamivudine + adefovir: −0.39 [−42.48, 41.21]). At 1 year, the change in eGFR from baseline was significantly higher with telbivudine compared to other NAs.

Conclusion

The systematic literature review and network meta-analysis provide evidence that telbivudine is associated with significant improvement in renal function in patients with CHB, either alone or in combination with other NAs.

Funding

Novartis Pharma AG.
Appendix
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Literature
1.
go back to reference European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol. 2012;57:167–85.CrossRef European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol. 2012;57:167–85.CrossRef
3.
go back to reference Combes B, Shorey J, Barrera A, et al. Glomerulonephritis with deposition of Australia antigen-antibody complexes in glomerular basement membrane. Lancet. 1971;2:234–7.CrossRefPubMed Combes B, Shorey J, Barrera A, et al. Glomerulonephritis with deposition of Australia antigen-antibody complexes in glomerular basement membrane. Lancet. 1971;2:234–7.CrossRefPubMed
4.
go back to reference Chacko EC, Surrun SK, Mubarack Sani TP, Pappachan JM. Chronic viral hepatitis and chronic kidney disease. Postgrad Med J. 2010;86:486–92.CrossRefPubMed Chacko EC, Surrun SK, Mubarack Sani TP, Pappachan JM. Chronic viral hepatitis and chronic kidney disease. Postgrad Med J. 2010;86:486–92.CrossRefPubMed
5.
6.
go back to reference Yi Z, Jie YW, Nan Z. The efficacy of anti-viral therapy on hepatitis B virus-associated glomerulonephritis: a systematic review and meta-analysis. Ann Hepatol. 2011;10:165–73.PubMed Yi Z, Jie YW, Nan Z. The efficacy of anti-viral therapy on hepatitis B virus-associated glomerulonephritis: a systematic review and meta-analysis. Ann Hepatol. 2011;10:165–73.PubMed
7.
go back to reference Lai KN, Li PK, Lui SF, et al. Membranous nephropathy related to hepatitis B virus in adults. N Engl J Med. 1991;324:1457–63.CrossRefPubMed Lai KN, Li PK, Lui SF, et al. Membranous nephropathy related to hepatitis B virus in adults. N Engl J Med. 1991;324:1457–63.CrossRefPubMed
8.
go back to reference Appel G. Viral infections and the kidney: HIV, hepatitis B, and hepatitis C. Cleve Clin J Med. 2007;74:353–60.CrossRefPubMed Appel G. Viral infections and the kidney: HIV, hepatitis B, and hepatitis C. Cleve Clin J Med. 2007;74:353–60.CrossRefPubMed
9.
go back to reference Fontana RJ. Side effects of long-term oral antiviral therapy for hepatitis B. Hepatology. 2009;49(Suppl):S185–95.CrossRefPubMed Fontana RJ. Side effects of long-term oral antiviral therapy for hepatitis B. Hepatology. 2009;49(Suppl):S185–95.CrossRefPubMed
10.
go back to reference Deray G, Buti M, Gane E, et al. Hepatitis B virus infection and the kidney: renal abnormalities in HBV patients, antiviral drugs handling, and specific follow-up. Adv Hepatol. 2015;2015:11. doi:10.1155/2015/596829 (article ID 596829).CrossRef Deray G, Buti M, Gane E, et al. Hepatitis B virus infection and the kidney: renal abnormalities in HBV patients, antiviral drugs handling, and specific follow-up. Adv Hepatol. 2015;2015:11. doi:10.​1155/​2015/​596829 (article ID 596829).CrossRef
11.
go back to reference Deterding K, Lampe N, Reijnders J, et al. Prevalence and severity of kidney dysfunction in patients with chronic hepatitis B in Europe: data from the European VIRGIL cohort. In: Abstracts of the 46th Annual Meeting of the European Association for the Study of the Liver. Berlin: European Association for the Study of Liver; 2011. Abstract number 366. Deterding K, Lampe N, Reijnders J, et al. Prevalence and severity of kidney dysfunction in patients with chronic hepatitis B in Europe: data from the European VIRGIL cohort. In: Abstracts of the 46th Annual Meeting of the European Association for the Study of the Liver. Berlin: European Association for the Study of Liver; 2011. Abstract number 366.
12.
go back to reference Mauss S, Berger F, Filmann N, et al. Effect of HBV polymerase inhibitors on renal function in patients with chronic hepatitis B. J Hepatol. 2011;55:1235–40.CrossRefPubMed Mauss S, Berger F, Filmann N, et al. Effect of HBV polymerase inhibitors on renal function in patients with chronic hepatitis B. J Hepatol. 2011;55:1235–40.CrossRefPubMed
13.
go back to reference Kim YJ, Cho HC, Sinn DH, et al. Frequency and risk factors of renal impairment during long-term adefovir dipivoxil treatment in chronic hepatitis B patients. J Gastroenterol Hepatol. 2012;27:306–12.CrossRefPubMed Kim YJ, Cho HC, Sinn DH, et al. Frequency and risk factors of renal impairment during long-term adefovir dipivoxil treatment in chronic hepatitis B patients. J Gastroenterol Hepatol. 2012;27:306–12.CrossRefPubMed
16.
go back to reference Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–9.CrossRefPubMed Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–9.CrossRefPubMed
17.
go back to reference Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health. 1998;52:377–84.CrossRefPubMedPubMedCentral Downs SH, Black N. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. J Epidemiol Community Health. 1998;52:377–84.CrossRefPubMedPubMedCentral
18.
go back to reference Hoaglin DC, Hawkins N, Jansen JP, et al. Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 2. Value Health. 2011;14:429–37.CrossRefPubMed Hoaglin DC, Hawkins N, Jansen JP, et al. Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 2. Value Health. 2011;14:429–37.CrossRefPubMed
19.
go back to reference Dias S, Sutton AJ, Ades AE, Welton NJ. Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta-analysis of randomized controlled trials. Med Decis Mak. 2013;33:607–17.CrossRef Dias S, Sutton AJ, Ades AE, Welton NJ. Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta-analysis of randomized controlled trials. Med Decis Mak. 2013;33:607–17.CrossRef
20.
go back to reference Dias S, Welton NJ, Sutton AJ, Caldwell DM, Lu G, Ades AE. Evidence synthesis for decision making 4: inconsistency in networks of evidence based on randomized controlled trials. Med Decis Mak. 2013;33:641–56.CrossRef Dias S, Welton NJ, Sutton AJ, Caldwell DM, Lu G, Ades AE. Evidence synthesis for decision making 4: inconsistency in networks of evidence based on randomized controlled trials. Med Decis Mak. 2013;33:641–56.CrossRef
21.
go back to reference Rooprai R, Nijhawan S. Comparative evaluation of renal function in patients of chronic hepatitis B treated with nucleos(t)ide analogues. Hepatol Int. 2013;7:S185. Rooprai R, Nijhawan S. Comparative evaluation of renal function in patients of chronic hepatitis B treated with nucleos(t)ide analogues. Hepatol Int. 2013;7:S185.
22.
go back to reference Esaulenko E, Stukov BV, Nikitina OE. Evaluation of patient characteristics and efficacy with entecavir and telbivudine treatment in Russian patients with chronic hepatitis B. Hepatol Int. 2013;7:S191. Esaulenko E, Stukov BV, Nikitina OE. Evaluation of patient characteristics and efficacy with entecavir and telbivudine treatment in Russian patients with chronic hepatitis B. Hepatol Int. 2013;7:S191.
23.
go back to reference Krastev Z, Kotzev IA, Celen MK, McNeeley D, Hamed KA. Efficacy and safety of telbivudine versus tenofovir treatment based on the Roadmap concept: results from a randomized, controlled trial in HBeAg-negative chronic hepatitis B patients. Hepatology. 2014;60:1104A. Krastev Z, Kotzev IA, Celen MK, McNeeley D, Hamed KA. Efficacy and safety of telbivudine versus tenofovir treatment based on the Roadmap concept: results from a randomized, controlled trial in HBeAg-negative chronic hepatitis B patients. Hepatology. 2014;60:1104A.
24.
go back to reference Park H, Park JY, Kim SU, et al. A prospective randomized trial of switching to telbivudine plus adefovir in HBeAg-positive lamivudine-resistant chronic hepatitis B patients who have suboptimal response to lamivudine plus adefovir. Clin Gastroenterol Hepatol. 2014;12:157.CrossRef Park H, Park JY, Kim SU, et al. A prospective randomized trial of switching to telbivudine plus adefovir in HBeAg-positive lamivudine-resistant chronic hepatitis B patients who have suboptimal response to lamivudine plus adefovir. Clin Gastroenterol Hepatol. 2014;12:157.CrossRef
25.
go back to reference Izzedine H, Hulot JS, Launay-Vacher V, et al. Renal safety of adefovir dipivoxil in patients with chronic hepatitis B: two double-blind, randomized, placebo-controlled studies. Kidney Int. 2004;66:1153–8.CrossRefPubMed Izzedine H, Hulot JS, Launay-Vacher V, et al. Renal safety of adefovir dipivoxil in patients with chronic hepatitis B: two double-blind, randomized, placebo-controlled studies. Kidney Int. 2004;66:1153–8.CrossRefPubMed
26.
go back to reference Lee S, Park JY, Song K, et al. Comparison of the effects of telbivudine and entecavir treatment on estimated glomerular filtration rate in patients with chronic hepatitis B. Gut Liver. 2015;9:776–83.CrossRefPubMedPubMedCentral Lee S, Park JY, Song K, et al. Comparison of the effects of telbivudine and entecavir treatment on estimated glomerular filtration rate in patients with chronic hepatitis B. Gut Liver. 2015;9:776–83.CrossRefPubMedPubMedCentral
27.
go back to reference Hung CH, Chen CH, Lu SN, Hu TH, Wang JH, Lee CM. Tenofovir versus entecavir in the treatment of chronic hepatitis B with severe acute exacerbation. Hepatology. 2014;60:1118A.CrossRef Hung CH, Chen CH, Lu SN, Hu TH, Wang JH, Lee CM. Tenofovir versus entecavir in the treatment of chronic hepatitis B with severe acute exacerbation. Hepatology. 2014;60:1118A.CrossRef
28.
go back to reference Ha NB, Ha NB, Garcia RT, et al. Renal dysfunction in chronic hepatitis B patients treated with adefovir dipivoxil. Hepatology. 2009;50:727–34.CrossRefPubMed Ha NB, Ha NB, Garcia RT, et al. Renal dysfunction in chronic hepatitis B patients treated with adefovir dipivoxil. Hepatology. 2009;50:727–34.CrossRefPubMed
29.
go back to reference Su PY, Yen HH, Hsu YC, Wu SS, Su WW, Soon MS. Renal function for chronic hepatitis B patients treated with nucleoside antivirals—a retrospective study in a medical center. Hepatol Int. 2013;7:S222. Su PY, Yen HH, Hsu YC, Wu SS, Su WW, Soon MS. Renal function for chronic hepatitis B patients treated with nucleoside antivirals—a retrospective study in a medical center. Hepatol Int. 2013;7:S222.
30.
go back to reference Chan HLY, Chen YC, Gane EJ, et al. Randomized clinical trial: efficacy and safety of telbivudine and lamivudine in treatment-naive patients with HBV-related decompensated cirrhosis. J Viral Hepat. 2012;19:732–43.CrossRefPubMed Chan HLY, Chen YC, Gane EJ, et al. Randomized clinical trial: efficacy and safety of telbivudine and lamivudine in treatment-naive patients with HBV-related decompensated cirrhosis. J Viral Hepat. 2012;19:732–43.CrossRefPubMed
31.
go back to reference Gane EJ, Deray G, Liaw YF, et al. Telbivudine improves renal function in patients with chronic hepatitis b. Gastroenterology. 2014;146(138–46):e5.PubMed Gane EJ, Deray G, Liaw YF, et al. Telbivudine improves renal function in patients with chronic hepatitis b. Gastroenterology. 2014;146(138–46):e5.PubMed
32.
go back to reference Koklu S, Gulsen MT, Tuna Y, et al. Differences in nephrotoxicity risk and renal effects among anti-viral therapies against hepatitis B. Aliment Pharmacol Ther. 2015;41:310–9.CrossRefPubMed Koklu S, Gulsen MT, Tuna Y, et al. Differences in nephrotoxicity risk and renal effects among anti-viral therapies against hepatitis B. Aliment Pharmacol Ther. 2015;41:310–9.CrossRefPubMed
33.
go back to reference Hu TH, Chang KC, Tseng PL, Lin MT, Hung CH, Yen YH. A comparison of renal safety of telbivudine entecavir and tenofovir treatment in chronic hepatitis B patients: a single center large “real life” cohort study. Hepatol Int. 2015;1:S186. Hu TH, Chang KC, Tseng PL, Lin MT, Hung CH, Yen YH. A comparison of renal safety of telbivudine entecavir and tenofovir treatment in chronic hepatitis B patients: a single center large “real life” cohort study. Hepatol Int. 2015;1:S186.
34.
go back to reference Piratvisuth T, Komolmit P, Tanwandee T, et al. 52-Week efficacy and safety of telbivudine with conditional tenofovir intensification at week 24 in HBeAg-positive chronic hepatitis B. PLoS One. 2013;8:e54279.CrossRefPubMedPubMedCentral Piratvisuth T, Komolmit P, Tanwandee T, et al. 52-Week efficacy and safety of telbivudine with conditional tenofovir intensification at week 24 in HBeAg-positive chronic hepatitis B. PLoS One. 2013;8:e54279.CrossRefPubMedPubMedCentral
35.
go back to reference Sun H, Zhang S, Wang M. Efficacy and safety of three different treatments in 183 patients with hepatitis B cirrhosis. Hepatol Int. 2014;1:S69. Sun H, Zhang S, Wang M. Efficacy and safety of three different treatments in 183 patients with hepatitis B cirrhosis. Hepatol Int. 2014;1:S69.
36.
go back to reference Tsai MC, Chen CH, Hung CH, et al. A comparison of efficacy and safety of 2-year telbivudine and entecavir treatment in patients with chronic hepatitis B: a match-control study. Clin Microbiol Infect. 2014;20:O90–100.CrossRefPubMed Tsai MC, Chen CH, Hung CH, et al. A comparison of efficacy and safety of 2-year telbivudine and entecavir treatment in patients with chronic hepatitis B: a match-control study. Clin Microbiol Infect. 2014;20:O90–100.CrossRefPubMed
37.
go back to reference Tsai MC, Hung CH, Chen CH, et al. Comparing the change of renal function of tenofovir and telbivudine naive chronic hepatitis B patients. Hepatol Int. 2014;1:S154. Tsai MC, Hung CH, Chen CH, et al. Comparing the change of renal function of tenofovir and telbivudine naive chronic hepatitis B patients. Hepatol Int. 2014;1:S154.
38.
go back to reference Tsai MC, Chen CH, Tseng PL, et al. Comparison of renal safety and efficacy of telbivudine, entecavir and tenofovir treatment in chronic hepatitis B patients: real world experience. Clin Microbiol Infect. 2016;22(95):e1–7. Tsai MC, Chen CH, Tseng PL, et al. Comparison of renal safety and efficacy of telbivudine, entecavir and tenofovir treatment in chronic hepatitis B patients: real world experience. Clin Microbiol Infect. 2016;22(95):e1–7.
39.
go back to reference Tien C, Xu JJ, Chan LS, et al. Long-term treatment with tenofovir in Asian-American chronic hepatitis B patients is associated with abnormal renal phosphate handling. Dig Dis Sci. 2015;60:566–72.CrossRefPubMed Tien C, Xu JJ, Chan LS, et al. Long-term treatment with tenofovir in Asian-American chronic hepatitis B patients is associated with abnormal renal phosphate handling. Dig Dis Sci. 2015;60:566–72.CrossRefPubMed
40.
go back to reference Qi X, Wang JY, Mao RC, Zhang JM. Impact of nucleos(t)ide analogues on the estimated glomerular filtration rate in patients with chronic hepatitis B: a prospective cohort study in China. J Viral Hepat. 2015;22:46–54.CrossRefPubMed Qi X, Wang JY, Mao RC, Zhang JM. Impact of nucleos(t)ide analogues on the estimated glomerular filtration rate in patients with chronic hepatitis B: a prospective cohort study in China. J Viral Hepat. 2015;22:46–54.CrossRefPubMed
41.
go back to reference Liang KH, Chen YC, Hsu CW, Chang ML, Yeh CT. Decrease of serum angiotensin converting enzyme levels upon telbivudine treatment for chronic hepatitis B virus infection and negative correlations between the enzyme levels and estimated glomerular filtration rates. Hepat Mon. 2014;14:e15074.CrossRefPubMedPubMedCentral Liang KH, Chen YC, Hsu CW, Chang ML, Yeh CT. Decrease of serum angiotensin converting enzyme levels upon telbivudine treatment for chronic hepatitis B virus infection and negative correlations between the enzyme levels and estimated glomerular filtration rates. Hepat Mon. 2014;14:e15074.CrossRefPubMedPubMedCentral
42.
go back to reference Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B. N Engl J Med. 2003;348:800–7.CrossRefPubMed Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B. N Engl J Med. 2003;348:800–7.CrossRefPubMed
43.
go back to reference Papatheodoridis G, Buti M, Cornberg M, et al. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol. 2012;57:167–85.CrossRef Papatheodoridis G, Buti M, Cornberg M, et al. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol. 2012;57:167–85.CrossRef
44.
go back to reference Wang Y, Thongsawat S, Gane EJ, et al. Efficacy and safety of continuous 4-year telbivudine treatment in patients with chronic hepatitis B. J Viral Hepat. 2013;20:e37–46.CrossRefPubMedPubMedCentral Wang Y, Thongsawat S, Gane EJ, et al. Efficacy and safety of continuous 4-year telbivudine treatment in patients with chronic hepatitis B. J Viral Hepat. 2013;20:e37–46.CrossRefPubMedPubMedCentral
45.
go back to reference Yang Q, Shi YU, Yang Y, Lou G, Lv F. Association between adefovir dipivoxil treatment and the risk of renal insufficiency in patients with chronic hepatitis B: a meta-analysis. Biomed Rep. 2015;3:269–75.PubMedPubMedCentral Yang Q, Shi YU, Yang Y, Lou G, Lv F. Association between adefovir dipivoxil treatment and the risk of renal insufficiency in patients with chronic hepatitis B: a meta-analysis. Biomed Rep. 2015;3:269–75.PubMedPubMedCentral
Metadata
Title
Renal Function in Nucleos(t)ide Analog-Treated Patients With Chronic Hepatitis B: A Systematic Literature Review and Network Meta-Analysis
Authors
Henry L. Y. Chan
Javed Shaikh
Subhajit Gupta
Kamal Hamed
Publication date
01-05-2016
Publisher
Springer Healthcare
Published in
Advances in Therapy / Issue 5/2016
Print ISSN: 0741-238X
Electronic ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-016-0337-2

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