Meta-Analysis
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2019; 25(23): 2961-2972
Published online Jun 21, 2019. doi: 10.3748/wjg.v25.i23.2961
Comparison of renal safety of tenofovir and entecavir in patients with chronic hepatitis B: Systematic review with meta-analysis
Hyo-Young Lee, Hyunwoo Oh, Chan-Hyuk Park, Yee-Hui Yeo, Mindie H Nguyen, Dae-Won Jun
Hyo-Young Lee, Hyunwoo Oh, Dae-Won Jun, Department of Internal Medicine, Hanyang University College of Medicine, Seoul 04763, South Korea
Chan-Hyuk Park, Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri 11923, South Korea
Yee-Hui Yeo, Mindie H Nguyen, Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford University, Stanford 94305, CA, United States
Author contributions: Lee HY contributed to study concept, data search, data extraction and analysis, and drafting of the manuscript; Oh H contributed to study concept, data search, data extraction and analysis, and drafting of the manuscript; Park CH contributed to critical revision of the manuscript; Yeo YH contributed to critical revision of the manuscript; Nguyen MH contributed to supervision, revision of the manuscript; Jun DW contributed to study concept, supervision, revision of the manuscript, guarantor of the article.
Conflict-of-interest statement: The authors deny any conflict of interest.
PRISMA 2009 Checklist statement: The manuscript has been checked according to PRISMA 2009 Checklist.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Dae-Won Jun, MD, PhD, Professor, Department of Internal Medicine, Hanyang University College of Medicine, 17 Haengdang-dong Sungdong-gu, Seoul 04763, South Korea. noshin@hanyang.ac.kr
Telephone: +82-2-22908338 Fax: +82-2-9720068
Received: March 22, 2019
Peer-review started: March 22, 2019
First decision: April 4, 2019
Revised: April 27, 2019
Accepted: May 8, 2019
Article in press: May 8, 2019
Published online: June 21, 2019
Processing time: 91 Days and 8.1 Hours
Abstract
BACKGROUND

Recently, the American Association for the Study of Liver Disease suggested no preference between tenofovir (TDF) and entecavir (ETV) regarding potential long-term risks of renal complications. Over the years, renal safety has become a critical concern in nucleos(t)ide analog-treated patients due to the long-term use of these drugs. However, existing studies do not show significant differences in renal dysfunction between these two drugs. Further, there is a paucity of studies comparing the long-term renal effects of TDF and ETV.

AIM

To investigate the effects of TDF and ETV on renal function, we performed systematic review and meta-analysis.

METHODS

Two investigators independently searched the Cochrane Library, MEDLINE, and Embase databases for randomized controlled trials and nonrandomized studies (NRSs) using the keywords “CHB”, “Tenofovir”, and “Entecavir”, and additional references were obtained from the bibliographies of relevant articles published through December 2017. The quality of each study was assessed using the Newcastle-Ottawa scale and the Grading of Recommendations Assessment, Development and Evaluation criteria. The primary outcome was the change in serum creatinine level in the TDF and ETV groups at baseline, 6 mo, 12 mo and 24 mo.

RESULTS

Nine NRSs comprising 2263 participants met the inclusion criteria. Changes in creatinine levels were higher in the TDF group than in the ETV group at 6 mo [mean difference (MD) = 0.03 mg/dL; 95%CI: 0.02-0.04; I2 = 0%], 12 mo (MD = 0.05 mg/dL; 95%CI: 0.02-0.08; I2 = 78%), and 24 mo (MD = 0.07 mg/dL; 95%CI: 0.01-0.13; I2 = 93%). The change in estimated glomerular filtration rate (eGFR) was significantly higher in the TDF group than in the ETV group at 6 mo [standardized mean difference (SMD), -0.22; 95%Cl: -0.36--0.08; I2 = 0%], 12 mo (SMD = -0.24; 95%Cl: -0.43--0.05; I2 = 50%), and 24 mo (-0.35; 95%Cl: -0.61- -0.09; I2 = 67%).

CONCLUSION

TDF statistically significantly increased serum creatinine levels and decreased the eGFR in 6-24 mo compared to ETV, with moderate to low quality of evidence. However, the differences are negligible.

Keywords: Hepatitis B; Chronic; Tenofovir; Entecavir; Safety; Review; Systematic; Meta-analysis

Core tip: Recently, the American Association for the Study of Liver Disease suggested no preference between tenofovir (TDF) and entecavir (ETV) regarding potential long-term risks of renal complications. Over the years, renal safety has become a critical concern in nucleos(t)ide analog-treated patients due to the long-term use of these drugs. However, the existing studies do not show significant differences between the two drugs in renal dysfunction. We believe that our study could resolve the existing debate. This is the first meta-analysis comparing the influence of the two drugs on renal function using continuous variables. TDF statistically significantly decreases renal function compared to ETV, but the difference is inappreciable.