Retrospective Cohort Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2018; 24(8): 917-928
Published online Feb 28, 2018. doi: 10.3748/wjg.v24.i8.917
Nationwide cohort study suggests that nucleos(t)ide analogue therapy decreases dialysis risk in Taiwanese chronic kidney disease patients acquiring hepatitis B virus infection
Yi-Chun Chen, Chung-Yi Li, Shiang-Jiun Tsai, Yen-Chun Chen
Yi-Chun Chen, Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi County 622, Taiwan
Yi-Chun Chen, School of Medicine, Tzu Chi University, Hualien 970, Taiwan
Chung-Yi Li, Department and Graduate Institute of Public Health, College of Medicine, National Cheng Hung University, Tainan 701, Taiwan
Chung-Yi Li, Department of Public Health, College of Public Health, China Medical University, Taichung 404, Taiwan
Shiang-Jiun Tsai, Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi County 622, Taiwan
Yen-Chun Chen, Division of Hepato-Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi County 622, Taiwan
Author contributions: Chen YC designed the research; Chen YC, Li CY and Tsai SJ performed the research; Chen YC, Li CY, Tsai SJ and Chen YC analyzed the data; Chen YC wrote the paper; Li CY, Tsai SJ, Chen YC critically revised the manuscript for important intellectual content.
Supported by Dalin Tzu Chi Hospital, No. DTCRD 104-I-16.
Institutional review board statement: This study was approved by the institutional review board of the Dalin Tzu Chi Hospital (B10302011).
Informed consent statement: All patients’ information was de-identified in the database (LHID2005) and no informed consent was required. This study was exempt from a full ethical review by the institutional review board of the Dalin Tzu Chi Hospital (B10302011).
Conflict-of-interest statement: All authors have no conflict of interests.
Data sharing statement: No additional data are available.
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/
Correspondence to: Yi-Chun Chen, MD, Assistant Professor, Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Road, Dalin Township, Chiayi County 622, Taiwan. chenyichun0320@yahoo.com.tw
Telephone: +886-5-2648000-5665 Fax: +886-5-2648128
Received: November 4, 2017
Peer-review started: November 4, 2017
First decision: November 22, 2017
Revised: December 10, 2017
Accepted: December 20, 2017
Article in press: December 20, 2017
Published online: February 28, 2018
Processing time: 114 Days and 21 Hours
ARTICLE HIGHLIGHTS
Research background

The evidence on whether HBV infection affects renal outcome in patients with chronic kidney disease (CKD) is limited. Here we retrospectively explored the association between HBV infection with and without nucleos(t)ide analogue use and the risk of end-stage renal disease (ESRD) in patients with CKD.

Research motivation

There is a significant and increasing burden of CKD, ESRD, and HBV infection in Taiwan and worldwide. CKD patients have an increased risk of acquiring chronic HBV infection. However, the effect of HBV infection and nucleos(t)ide analogue use on the risk of ESRD in CKD patients remains unclear. Taiwan provides an ideal setting for studying this relationship because it has a high prevalence of these three conditions.

Research objectives

To investigate the effect of HBV infection with and without nucleos(t)ide analogue use on the ESRD risk in Taiwanese CKD patients.

Research methods

By analyzing the Taiwan Longitudinal Health Insurance Database 2005, the authors used propensity score-matched and competing risk analyses to evaluate the effect of HBV infection with and without nucleos(t)ide analogue therapy on the development of ESRD in CKD patients. The authors used a modified Kaplan-Meier method and Gray’s method to calculate and compare the cumulative incidence of ESRD, and a modified Cox proportional hazard model in the presence of competing risk and stratified analyses to determine the ESRD risk between propensity-matched untreated HBV-infected and HBV-uninfected CKD patients as well as propensity-matched untreated and treated HBV-infected CKD patients. The authors also calculated the number of patients needed to be treated to yield one fewer ESRD.

Research results

In the propensity-matched untreated HBV-infected and HBV-uninfected CKD patients, the risk of ESRD was significantly higher in the untreated cohort (16-year cumulative incidence, 10.1%) than in the uninfected cohort (16-year cumulative incidence, 6.6%) with a significant adjusted hazard ratio of 1.67. In the propensity-matched HBV-treated and HBV-untreated CKD patients, the treated cohort (16-year cumulative incidence, 2.2%) had a significantly 87% reduced ESRD risk compared with the untreated cohort (16-year cumulative incidence, 11.9%). The number needed to treat for one fewer ESRD after NA use at 12 years was 12. Multivariable stratified analyses verified these associations in all subgroups. However, the cumulative ESRD incidence of the propensity-matched three cohorts warrants further prospective research because the propensity score matching cannot fit well in all treated, untreated, and uninfected CKD patients.

Research conclusions

To the best of our knowledge, this is the first study to investigate the incidence and renal outcome in CKD patients acquiring chronic HBV infection and to evaluate the renal effect of nucleos(t)ide analogue therapy and the number needed to treat for one fewer ESRD in HBV-infected CKD patients. This has long been a neglected issue because there is no recommendation in the K/DOQI guidelines on whether HBV serological evaluation should be carried out in CKD patients. This large retrospective cohort study suggests that the incidence of CKD patients acquiring HBV infection is 3.2% and that untreated HBV infection and nucleos(t)ide analogue therapy are associated with increased and decreased risk of ESRD, respectively, in CKD patients. These findings imply that HBV infection may have a role in the pathogenesis of renal injury, and that HBV suppression may improve renal outcome among CKD patients. Our findings will be helpful in the future CKD prevention care program that assesses HBV status in CKD patients.

Research perspectives

Future prospective study is warranted to confirm our findings and better understand the pathological mechanism underlying this association.