Prospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 27, 2020; 12(12): 1326-1340
Published online Dec 27, 2020. doi: 10.4254/wjh.v12.i12.1326
Subclinical proximal tubulopathy in hepatitis B: The roles of nucleot(s)ide analogue treatment and the hepatitis B virus
Anaïs Brayette, Marie Essig, Paul Carrier, Marilyne Debette-Gratien, Anaïs Labrunie, Sophie Alain, Marianne Maynard, Nathalie Ganne-Carrié, Eric Nguyen-Khac, Pauline Pinet, Victor De Ledinghen, Christophe Renou, Philippe Mathurin, Claire Vanlemmens, Vincent Di Martino, Anne Gervais, Juliette Foucher, Fouchard-Hubert Isabelle, Julien Vergniol, Isabelle Hourmand-Ollivier, Daniel Cohen, Xavier Duval, Thierry Poynard, Marc Bardou, Armand Abergel, Manh-Thong Dao, Thierry Thévenot, Jean-Baptiste Hiriart, Valérie Canva, Guillaume Lassailly, Christine Aurières, Nathalie Boyer, Dominique Thabut, Pierre-Henri Bernard, Matthieu Schnee, Dominique Larrey, Bertrand Hanslik, Séverine Hommel, Jérémie Jacques, Véronique Loustaud-Ratti
Anaïs Brayette, Paul Carrier, Marilyne Debette-Gratien, Jérémie Jacques, Véronique Loustaud-Ratti, U1248 INSERM, Department of Hepatology and Gastroenterology, Univ. Limoges, CHU Limoges, Limoges F-87000, France
Marie Essig, U1248 INSERM, Department of Nephrology and Transplantation, CHU Limoges, Limoges F-87000, France
Anaïs Labrunie, Department of Center of Epidemiology, Biostatistics and Research Methodology, CHU Limoges, Limoges F-87000, France
Sophie Alain, U1092 INSERM, Department of Virology, CHU Limoges, Limoges F-87000, France
Marianne Maynard, Department of Hepatology, Croix-Rousse University Hospital of Lyon, Lyon 69004, France
Nathalie Ganne-Carrié, Department of Hepatology, Jean Verdier University Hospital of Bondy, Bondy 93140, France
Eric Nguyen-Khac, Department of Hepato-Gastroenterology, Amiens University Hospital, Amiens 80054, France
Pauline Pinet, Department of Infectious Diseases, CHU Limoges, Limoges F-87000, France
Victor De Ledinghen, Juliette Foucher, Julien Vergniol, Jean-Baptiste Hiriart, Department of Hepatology, Haut Leveque Hospital, Bordeaux University Hospital, Pessac 33604, France
Christophe Renou, Department of Gastroenterology, Hyeres Hospital, Hyeres 83407, France
Philippe Mathurin, Valérie Canva, Guillaume Lassailly, Department of Hepato-Gastroenterology, Claude Huriez University Hospital, Lille 59037, France
Claire Vanlemmens, Vincent Di Martino, Thierry Thévenot, Department of Hepatology, Jean Minjoz University Hospital, Besançon 25030, France
Anne Gervais, Xavier Duval, Department of Infectious Diseases, Bichat University Hospital, Paris 75018, France
Fouchard-Hubert Isabelle, Department of Hepatology, University Hospital of Angers, Angers 49933, France
Isabelle Hourmand-Ollivier, Manh-Thong Dao, Department of Hepato-Gastroenterology and Nutrition, University Hospital of Caen, Caen 14033, France
Daniel Cohen, Department of General Medecine, University Hospital of Caen, Caen 14000, France
Thierry Poynard, Dominique Thabut, Department of Hepatology, La Pitié-Salpêtrière University Hospital, Paris 75651, France
Marc Bardou, Department of Hepatology and Gastroenterology, Dijon University Hospital, Dijon 21079, France
Armand Abergel, Department of Hepatology and Gastroenterology, Estaing University Hospital, Clermont Ferrand 63003, France
Christine Aurières, Nathalie Boyer, Department of Hepatology, Beaujon University Hospital, Clichy 92110, France
Pierre-Henri Bernard, Department of Hepatology, Saint-André University Hospital, Bordeaux 33000, France
Matthieu Schnee, Department of Hepatology and Gastroenterology, La Roche-Sur-Yon Hospital Center, La Roche-Sur-Yon 85000, France
Dominique Larrey, Department of Hepatology and Gastroenterology, University Hospital of Montpellier, Montpellier 34295, France
Bertrand Hanslik, Department of Addictology, Hospital of Montpellier, Montpellier 34295, France
Séverine Hommel, Department of Hepatology and Gastroenterology, Hospital Center of Aix en Provence, Aix-en-Provence 13100, France
Author contributions: Brayette A, Essig M, Carrier P, Labrunie A, and Loustaud-Ratti V analyzed and interpreted the data; Brayette A, Carrier P and Loustaud-Ratti V drafted the manuscript; Loustaud-Ratti V and Essig M carried out study concept and design; Carrier P, Debette-Gratien M, Alain S, Maynard M, Ganne-Carrié N, Khac EN, Pinet P, De Ledinghen V, Renou C, Mathurin P, Vanlemmens C, Di Martino V, Gervais A, Foucher J, Isabelle FH, Vergniol J, Hourmand-Ollivier I, Cohen D, Duval X, Poynard T, Bardou M, Abergel A, Dao MT, Thevenot T, Hiriart JB, Canva V, Lassailly G, Aurières C, Boyer N, Thabut D, Bernard PH, Schnee M, Larrey D, Hanslik B, Hommel S, Jacques J, and Loustaud-Ratti V collected the data; Labrunie A performed statistical analysis; Loustaud-Ratti V obtained funding; All authors critically revised the manuscript.
Supported by Bristol Myers Squibb, France.
Institutional review board statement: The study was reviewed and approved by the French Institutional Review Board AFSSAPS, No. A111378-30.
Conflict-of-interest statement: Pr. Loustaud-Ratti reports grants from Bristol Myers Squibb, France, during the conduct of the study; personal fees from GILEAD, personal fees from ABBVIE, personal fees from MSD, grants from BMS, outside the submitted work. Dr. Carrier reports non-financial support from GILEAD, non-financial support from ABBVIE, non-financial support from MSD, non-financial support from BMS, outside the submitted work. Other authors declare no conflict of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at veronique.loustaud-ratti@unilim.fr. Participants gave informed consent for data sharing.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: Véronique Loustaud-Ratti, MD, PhD, Professor, U1248 INSERM, Department of Hepatology and Gastroenterology, Univ. Limoges, CHU Limoges, 2, Avenue Martin Luther King, Limoges F-87000, France. veronique.loustaud-ratti@unilim.fr
Received: June 11, 2020
Peer-review started: June 11, 2020
First decision: September 18, 2020
Revised: October 7, 2020
Accepted: October 28, 2020
Article in press: October 28, 2020
Published online: December 27, 2020
Processing time: 189 Days and 14.9 Hours
Core Tip

Core Tip: The objective of this prospective, multicenter study was to determine the 24 mo prevalence and incidence of subclinical proximal tubulopathy (SPT) in hepatitis B virus (HBV)-monoinfected patients that were either treatment-naïve or treated with nucleot(s)ide analogues. Data on early SPT markers, the estimated glomerular filtration rate and phosphatemia, were collected quarterly from 196 patients. The prevalence and incidence of SPT was higher in tenofovir disoproxil-treated patients compared to naïve patients. The median survival time without SPT (time during which more than 50% of the patients remained SPT-free), evaluated only in the tenofovir disoproxil-treated group, was 5.9 mo. SPT was detected in the naïve population, indicating possible HBV-induced toxicity in renal tubules.