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
ARTICLE HIGHLIGHTS
Research background

Tenofovir (TDF) and entecavir (ETV) are preferred first-line treatments for chronic hepatitis B (CHB). The long-term safety issue of nucleos(t)ide analog is very important because CHB patients should take it indefinitely. In addition, a number of researchers have recently reported many CHB patients suffer from CKD through large-scale studies.

Research motivation

Over the years, several studies have been conducted to compare renal safety of the two drugs, but the results varied and sometimes conflicted with each other. Confusedly, the recom-mendations of the recent two guidelines are contradictory.

Research objectives

We aimed to conduct a systematic review and meta-analysis to assess renal safety of TDF and ETV in patients with CHB using continuous variables.

Research methods

Calculating the change of creatinine and estimated glomerular filtration rate (eGFR), we secured the distinction from the prior meta-analysis that using dichotomous data. To enhance the clinical importance, we performed sensitivity analysis with meta-regression.

Research results

With nine NRSs, we conducted meta-analysis. 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 to 0.08; I2 = 78%), and 24 mo (MD = 0.07 mg/dL; 95%CI: 0.01-0.13; I2 = 93%). The change in 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 to -0.05; I2 = 50%), and 24 mo (-0.35; 95%Cl: -0.61--0.09; I2 = 67%).

Research conclusions

Until now, in studies comparing the effect on renal function between the two drugs, the di-fferences varied greatly. However, our study found that the difference was negligible.

Research perspectives

The value of creatinine and eGFR in our meta-analysis was a secondary outcome in most of the included studies. And most of the studies used various eGFR formula and different AKI definitions. We need further research comparing renal function as a primary outcome and using universal definition of AKI, if possible, through large-scale RCT.