{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T12:37:20Z","timestamp":1784291840039,"version":"3.55.0"},"reference-count":41,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"name":"Shenzhen Third People\u2019s Hospital Research Fund","award":["24250G1006"],"award-info":[{"award-number":["24250G1006"]}]},{"name":"Shenzhen Third People\u2019s Hospital Research Fund","award":["G2022110"],"award-info":[{"award-number":["G2022110"]}]},{"name":"Shenzhen Third People\u2019s Hospital Research Fund","award":["22244G4001"],"award-info":[{"award-number":["22244G4001"]}]},{"name":"Shenzhen Science and Technology Research and Development Fund","award":["JCYJ20190809143609762"],"award-info":[{"award-number":["JCYJ20190809143609762"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n               <jats:title>Background<\/jats:title>\n               <jats:p>For individuals with chronic hepatitis B (CHB) at higher risk of nephrotoxicity, entecavir (ETV) and tenofovir alafenamide (TAF) are recommended antiviral options. This study aimed to investigate kidney safety among treatment-na\u00efve individuals with CHB receiving TAF versus ETV.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Method<\/jats:title>\n               <jats:p>Treatment-na\u00efve individuals with CHB receiving either TAF or ETV from July 2019 to December 2020 were included. Follow-up data on estimated glomerular filtration rates (eGFR) were collected. Factors related to chronic kidney disease (CKD) development were analyzed by Cox regression analysis. Generalized additive mixed model (GAMM) was employed to investigate temporal eGFR changes and the association between the extent of follow-up eGFR change and antiviral agents.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Results<\/jats:title>\n               <jats:p>466 treatment-na\u00efve individuals with CHB were included, with 296 in the ETV group and 170 in the TAF group. In the subgroup of individuals with a baseline eGFR higher than 90 mL\/min\/1.73 m<jats:sup>2<\/jats:sup>, 13.9% in the ETV group developed CKD, compared to 9.8% in the TAF group (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.304). Multivariable Cox analysis demonstrated that male (hazard ratio (HR) 2.72; 95% confidence interval (CI) [1.02\u20137.25]; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.045) and baseline eGFR (HR 0.86; 95% CI [0.82\u20130.90]; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001) were significantly associate with the CKD development. GAMM revealed that eGFR initially decreased and then stabilized around week 40. Every 12 weeks, the TAF group exhibited an overall lower rate of eGFR decline compared to the ETV group, with an adjusted difference of 0.38\u00a0mL\/min\/1.73 m<jats:sup>2<\/jats:sup> (95% CI [0.11\u20130.65], <jats:italic>p<\/jats:italic>\u00a0=\u00a00.006). The difference remained significant in males and patients over 35 years old.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Conclusion<\/jats:title>\n               <jats:p>The kidney safety profile of TAF among treatment-na\u00efve individuals with CHB was comparable to that of ETV, without significant difference in developing CKD. Stratified analyses further revealed that TAF demonstrated superior kidney benefits compared to ETV specifically in males or patients aged over 35 years.<\/jats:p>\n            <\/jats:sec>","DOI":"10.7717\/peerj.19901","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T08:40:24Z","timestamp":1756197624000},"page":"e19901","source":"Crossref","is-referenced-by-count":3,"title":["Longitudinal changes in estimated glomerular filtration rates in chronic hepatitis B patients treated with Tenofovir Alafenamide <i>vs<\/i> Entecavir"],"prefix":"10.7717","volume":"13","author":[{"given":"Xuan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Liver Diseases, Shenzhen Third People\u2019s Hospital, Shenzhen, Guangdong, China"},{"name":"Phase I Clinical Trial Centre, Shenzhen Third People\u2019s Hospital, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Shenzhen Third People\u2019s Hospital, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Huang","sequence":"additional","affiliation":[{"name":"Medical Affairs Department, Shenzhen Third People\u2019s Hospital, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changxiang","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Liver Diseases, Shenzhen Third People\u2019s Hospital, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Shenzhen Third People\u2019s Hospital, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Shenzhen Third People\u2019s Hospital, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Liver Diseases, Shenzhen Third People\u2019s Hospital, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zeng","sequence":"additional","affiliation":[{"name":"Medical Affairs Department, Shenzhen Third People\u2019s Hospital, Shenzhen, Guangdong, China"},{"name":"Health Management Department, Shenzhen Third People\u2019s Hospital, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Liver Diseases, Shenzhen Third People\u2019s Hospital, Shenzhen, Guangdong, China"},{"name":"Medical Affairs Department, Shenzhen Third People\u2019s Hospital, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"10.7717\/peerj.19901\/ref-1","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.4254\/wjh.v12.i12.1326","article-title":"Subclinical proximal tubulopathy in hepatitis B: the roles of nucleot(s)ide analogue treatment and the hepatitis B virus","volume":"12","author":"Brayette","year":"2020","journal-title":"World Journal of Hepatology"},{"key":"10.7717\/peerj.19901\/ref-2","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/nrneph.2017.181","article-title":"Sex and gender disparities in the epidemiology and outcomes of chronic kidney disease","volume":"14","author":"Carrero","year":"2018","journal-title":"Nature Reviews. Nephrology"},{"key":"10.7717\/peerj.19901\/ref-3","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1111\/hepr.13504","article-title":"Japan society of hepatology guidelines for the management of hepatitis B virus infection: 2019 update","volume":"50","author":"Drafting Committee for Hepatitis Management Guidelines, the Japan Society of Hepatology","year":"2020","journal-title":"Hepatology Research"},{"key":"10.7717\/peerj.19901\/ref-4","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1053\/j.gastro.2011.12.061","article-title":"Epidemiology of viral hepatitis and hepatocellular carcinoma","volume":"142","author":"El-Serag\u00a0Hashem","year":"2012","journal-title":"Gastroenterology"},{"key":"10.7717\/peerj.19901\/ref-5","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.jhep.2017.03.021","article-title":"EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection","volume":"67","author":"European Association for the Study of\u00a0the Liver","year":"2017","journal-title":"Journal of Hepatology"},{"key":"10.7717\/peerj.19901\/ref-6","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1007\/s13730-019-00404-5","article-title":"A case of entecavir-induced Fanconi syndrome","volume":"8","author":"Fujii","year":"2019","journal-title":"CEN Case Reports"},{"key":"10.7717\/peerj.19901\/ref-7","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.intimp.2016.11.022","article-title":"The efficacy and safety comparison between tenofovir and entecavir in treatment of chronic hepatitis B and HBV related cirrhosis: a systematic review and meta-analysis","volume":"42","author":"Han","year":"2017","journal-title":"International Immunopharmacology"},{"key":"10.7717\/peerj.19901\/ref-8","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1159\/000519440","article-title":"Real-world single-center comparison of the safety and efficacy of entecavir, Tenofovir disoproxil fumarate, and Tenofovir alafenamide in patients with chronic hepatitis B","volume":"65","author":"Jeong","year":"2021","journal-title":"Intervirology"},{"key":"10.7717\/peerj.19901\/ref-9","first-page":"1","article-title":"2016 Chinese guidelines for the management of dyslipidemia in adults","volume":"15","author":"Joint committee issued Chinese guideline for the management of dyslipidemia in adults","year":"2018","journal-title":"Journal of Geriatric Cardiology"},{"issue":"5","key":"10.7717\/peerj.19901\/ref-10","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1111\/liv.15208","article-title":"Higher risk of kidney function decline with entecavir than tenofovir alafenamide in patients with chronic hepatitis B","volume":"42","author":"Jung","year":"2022","journal-title":"Liver International"},{"issue":"4","key":"10.7717\/peerj.19901\/ref-11","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1016\/j.cgh.2021.05.032","article-title":"Tenofovir is associated with higher risk of kidney function decline than Entecavir in patients with chronic hepatitis B","volume":"20","author":"Jung","year":"2022","journal-title":"Clinical Gastroenterology and Hepatology"},{"key":"10.7717\/peerj.19901\/ref-12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/kisup.2012.73","article-title":"KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"3","author":"Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work\u00a0Group","year":"2013","journal-title":"Kidney International Supplements"},{"key":"10.7717\/peerj.19901\/ref-13","doi-asserted-by":"publisher","first-page":"276","DOI":"10.3350\/cmh.2022.0084","article-title":"KASL clinical practice guidelines for management of chronic hepatitis B","volume":"28","author":"Korean Association for the Study of\u00a0the Liver\u00a0(KASL)","year":"2022","journal-title":"Clinical and Molecular Hepatology"},{"key":"10.7717\/peerj.19901\/ref-14","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1111\/apt.15901","article-title":"Treatment with tenofovir disoproxil fumarate or entecavir in chronic hepatitis B virus\u2014infected patients with renal impairment: results from a 7\u2014year, multicentre retrospective cohort study","volume":"52","author":"Lampertico","year":"2020","journal-title":"Alimentary Pharmacology & Therapeutics"},{"key":"10.7717\/peerj.19901\/ref-15","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1002\/jgh3.12481","article-title":"Bone and renal safety profile at 72 weeks after switching to tenofovir alafenamide in chronic hepatitis B patients","volume":"5","author":"Lee","year":"2020","journal-title":"JGH Open"},{"key":"10.7717\/peerj.19901\/ref-16","doi-asserted-by":"publisher","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Annals of Internal Medicine"},{"key":"10.7717\/peerj.19901\/ref-17","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1186\/s12879-021-06237-x","article-title":"Short-term and long-term safety and efficacy of tenofovir alafenamide, tenofovir disoproxil fumarate and entecavir treatment of acute-on-chronic liver failure associated with hepatitis B","volume":"21","author":"Li","year":"2021","journal-title":"BMC Infectious Diseases"},{"key":"10.7717\/peerj.19901\/ref-18","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s12876-017-0582-0","article-title":"Comparison of telbivudine and entecavir on the change of off- treatment eGFR after 3 years of treatment in non-cirrhotic chronic hepatitis B patients","volume":"17","author":"Lin","year":"2017","journal-title":"BMC Gastroenterology"},{"key":"10.7717\/peerj.19901\/ref-19","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1111\/1467-9868.00183","article-title":"Inference in generalized additive mixed models by using smoothing splines","volume":"61","author":"Lin","year":"1999","journal-title":"Journal of the Royal Statistical Society Series B: Statistical Methodology"},{"key":"10.7717\/peerj.19901\/ref-20","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1186\/s12876-023-03027-4","article-title":"Renal and bone side effects of long-term use of entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide fumarate in patients with Hepatitis B: a network meta-analysis","volume":"23","author":"Liu","year":"2023","journal-title":"BMC Gastroenterology"},{"key":"10.7717\/peerj.19901\/ref-21","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1007\/s12072-021-10271-x","article-title":"Longitudinal renal changes in chronic hepatitis B patients treated with entecavir versus TDF: a REAL-B study","volume":"16","author":"Mak","year":"2022","journal-title":"Hepatology International"},{"key":"10.7717\/peerj.19901\/ref-22","doi-asserted-by":"publisher","first-page":"1185492","DOI":"10.3389\/fmicb.2023.1185492","article-title":"Tenofovir alafenamide versus entecavir for treating hepatitis B virus-related acute-on-chronic liver failure: real-world study","volume":"14","author":"Peng","year":"2023","journal-title":"Frontiers in Microbiology"},{"key":"10.7717\/peerj.19901\/ref-23","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.jhep.2006.05.013","article-title":"The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide","volume":"45","author":"Perz\u00a0Joseph","year":"2006","journal-title":"Journal of Hepatology"},{"key":"10.7717\/peerj.19901\/ref-24","doi-asserted-by":"publisher","first-page":"2259","DOI":"10.1097\/QAD.0000000000002699","article-title":"Tenofovir alafenamide vs. tenofovir disoproxil fumarate: an updated meta-analysis of 14 894 patients across 14 trials","volume":"34","author":"Pilkington","year":"2020","journal-title":"AIDS"},{"key":"10.7717\/peerj.19901\/ref-25","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1093\/ckj\/sfx026","article-title":"Age-dependent reference intervals for estimated and measured glomerular filtration rate","volume":"10","author":"Pottel","year":"2017","journal-title":"Clinical Kidney Journal"},{"key":"10.7717\/peerj.19901\/ref-26","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1093\/ndt\/gfv454","article-title":"An estimated glomerular filtration rate equation for the full age spectrum","volume":"31","author":"Pottel","year":"2016","journal-title":"Nephrology Dialysis Transplantation"},{"key":"10.7717\/peerj.19901\/ref-27","doi-asserted-by":"publisher","first-page":"e646","DOI":"10.1097\/MD.0000000000000646","article-title":"Impact of Nucleos(t)ide analogue combination therapy on the estimated glomerular filtration rate in patients with chronic hepatitis B","volume":"94","author":"Qi","year":"2015","journal-title":"Medicine"},{"key":"10.7717\/peerj.19901\/ref-28","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.antiviral.2015.11.009","article-title":"Tenofovir alafenamide: a novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus","volume":"125","author":"Ray","year":"2016","journal-title":"Antiviral Research"},{"key":"10.7717\/peerj.19901\/ref-29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12072-015-9675-4","article-title":"Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update","volume":"10","author":"Sarin","year":"2016","journal-title":"Hepatology International"},{"key":"10.7717\/peerj.19901\/ref-30","doi-asserted-by":"publisher","first-page":"e2400","DOI":"10.1097\/MD.0000000000002400","article-title":"Risk factors for renal functional decline in chronic hepatitis B patients receiving oral antiviral agents","volume":"95","author":"Shin","year":"2016","journal-title":"Medicine"},{"key":"10.7717\/peerj.19901\/ref-31","doi-asserted-by":"publisher","first-page":"315","DOI":"10.3760\/cma.j.cn115791-20210221-00095","article-title":"Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition)","volume":"13","author":"Society Chinese\u00a0Diabetes","year":"2021","journal-title":"Chinese Journal of Diabetes Mellitus"},{"key":"10.7717\/peerj.19901\/ref-32","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1002\/hep.29800","article-title":"Update on prevention, diagnosis, and treatment and of chronic hepatitis B: AASLD 2018 hepatitis B guidance","volume":"67","author":"Terrault","year":"2018","journal-title":"Hepatology"},{"key":"10.7717\/peerj.19901\/ref-33","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1016\/j.cgh.2018.08.037","article-title":"Changes in renal function in patients with chronic HBV infection treated with tenofovir disoproxil fumarate vs entecavir","volume":"17","author":"Trinh","year":"2019","journal-title":"Clinical Gastroenterology and Hepatology"},{"key":"10.7717\/peerj.19901\/ref-34","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1111\/apt.14682","article-title":"Using the chronic kidney disease guidelines to evaluate the renal safety of tenofovir disoproxil fumarate in hepatitis B patients","volume":"47","author":"Tsai","year":"2018","journal-title":"Alimentary Pharmacology & Therapeutics"},{"key":"10.7717\/peerj.19901\/ref-35","doi-asserted-by":"publisher","first-page":"95.e1","DOI":"10.1016\/j.cmi.2015.05.035","article-title":"Comparison of renal safety and efficacy of telbivudine, entecavir and tenofovir treatment in chronic hepatitis B patients: real world experience","volume":"22","author":"Tsai","year":"2016","journal-title":"Clinical Microbiology and Infection"},{"issue":"1","key":"10.7717\/peerj.19901\/ref-36","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s12981-021-00380-w","article-title":"Tenofovir alafenamide nephrotoxicity: a case report and literature review","volume":"18","author":"Ueaphongsukkit","year":"2021","journal-title":"AIDS Research and Therapy"},{"key":"10.7717\/peerj.19901\/ref-37","first-page":"283","article-title":"Alcohol misuse and kidney injury: epidemiological evidence and potential mechanisms","volume":"38","author":"Varga","year":"2017","journal-title":"Alcohol Research: Current Reviews"},{"key":"10.7717\/peerj.19901\/ref-38","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1053\/j.ackd.2010.05.002","article-title":"The aging kidney: physiological changes","volume":"17","author":"Weinstein","year":"2010","journal-title":"Advances in Chronic Kidney Disease"},{"key":"10.7717\/peerj.19901\/ref-39","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1111\/apt.14945","article-title":"Chronic kidney disease progression in patients with chronic hepatitis B on tenofovir, entecavir, or no treatment","volume":"48","author":"Wong","year":"2018","journal-title":"Alimentary Pharmacology & Therapeutics"},{"key":"10.7717\/peerj.19901\/ref-40","article-title":"Hepatitis B","author":"World Health\u00a0Organization","year":"2023"},{"issue":"6","key":"10.7717\/peerj.19901\/ref-41","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.14218\/JCTH.2023.00320","article-title":"Guidelines for the prevention and treatment of chronic hepatitis B (version 2022)","volume":"11","author":"You","year":"2023","journal-title":"Journal of Clinical and Translational Hepatology"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/19901.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/19901.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/19901.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/19901.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T08:40:29Z","timestamp":1756197629000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/19901"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,26]]},"references-count":41,"alternative-id":["10.7717\/peerj.19901"],"URL":"https:\/\/doi.org\/10.7717\/peerj.19901","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,26]]},"article-number":"e19901"}}