Subclinical proximal tubulopathy in hepatitis B:The roles of nucleot(s)ide analogue treatment and the hepatitis B virus  

作　　者：Anais Brayette Marie Essig Paul Carrier Marilyne Debette-Gratien Anais Labrunie Sophie Alain Marianne Maynard Nathalie Ganne-Carrie 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 Thevenot Jean-Baptiste Hiriart Valerie Canva Guillaume Lassailly Christine Aurières Nathalie Boyer Dominique Thabut Pierre-Henri Bernard Matthieu Schnee Dominique Larrey Bertrand Hanslik Severine Hommel Jeremie Jacques Veronique Loustaud-Ratti 

机构地区：[1]U1248 INSERM,Department of Hepatology and Gastroenterology,Univ.Limoges,CHU Limoges,Limoges F-87000,France [2]U1248 INSERM,Department of Nephrology and Transplantation,CHU Limoges,Limoges F-87000,France [3]Department of Center of Epidemiology,Biostatistics and Research Methodology,CHU Limoges,Limoges F-87000,France [4]U1092 INSERM,Department of Virology,CHU Limoges,Limoges F-87000,France [5]Department of Hepatology,Croix-Rousse University Hospital of Lyon,Lyon 69004,France [6]Department of Hepatology,Jean Verdier University Hospital of Bondy,Bondy 93140,France [7]Department of Hepato-Gastroenterology,Amiens University Hospital,Amiens 80054,France [8]Department of Infectious Diseases,CHU Limoges,Limoges F-87000,France [9]Department of Hepatology,Haut Leveque Hospital,Bordeaux University Hospital,Pessac 33604,France [10]Department of Gastroenterology,Hyeres Hospital,Hyeres 83407,France [11]Department of Hepato-Gastroenterology,Claude Huriez University Hospital,Lille 59037,France [12]Department of Hepatology,Jean Minjoz University Hospital,Besançon 25030,France [13]Department of Infectious Diseases,Bichat University Hospital,Paris 75018,France [14]Department of Hepatology,University Hospital of Angers,Angers 49933,France [15]Department of Hepato-Gastroenterology and Nutrition,University Hospital of Caen,Caen 14033,France [16]Department of General Medecine,University Hospital of Caen,Caen 14000,France [17]Department of Hepatology,La Pitié-Salpêtrière University Hospital,Paris 75651,France [18]Department of Hepatology and Gastroenterology,Dijon University Hospital,Dijon 21079,France [19]Department of Hepatology and Gastroenterology,Estaing University Hospital,Clermont Ferrand 63003,France [20]Department of Hepatology,Beaujon University Hospital,Clichy 92110,France [21]Department of Hepatology,Saint-AndréUniversity Hospital,Bordeaux 33000,France [22]Department of Hepatology and Gastroenterology,La Roche-Sur-Yon Hospital Center,La Roche-Sur-Yon 85000,France [23]Department of Hepatology and Gastroenterology,Unive

出　　处：《World Journal of Hepatology》2020年第12期1326-1340,共15页世界肝病学杂志（英文版）（电子版）

摘　　要：BACKGROUND The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity,such as estimated glomerular filtration rate(eGFR)and phosphatemia,are late markers of proximal tubulopathy.Multiple early markers are available,but no consensus exists on their use.AIM To determine the 24 mo prevalence of subclinical proximal tubulopathy(SPT),as defined with early biomarkers,in treated vs untreated hepatitis B virus(HBV)-monoinfected patients.METHODS A prospective,non-randomized,multicenter study of HBV-monoinfected patients with a low number of renal comorbidities was conducted.The patients were separated into three groups:Naïve,starting entecavir(ETV)treatment,or starting tenofovir disoproxil(TDF)treatment.Data on the early markers of SPT,the eGFR and phosphatemia,were collected quarterly.SPT was defined as a maximal tubular reabsorption of phosphate/eGFR below 0.8 mmoL/L and/or uric acid fractional excretion above 10%.The prevalence and cumulative incidence of SPT at month 24(M24)were calculated.Quantitative data were analyzed using analyses of variance or Kruskal-Wallis tests,whereas chi-squared or Fisher’s exact tests were used to analyze qualitative data.Multivariate analyses were used to adjust for any potential confounding factors.RESULTS Of the 196 patients analyzed,138(84 naïve,28 starting ETV,and 26 starting TDF)had no SPT at inclusion.At M24,the prevalence of SPT was not statistically different between naïve and either treated group(21.1%vs 30.7%,P<0.42 and 50.0%vs 30.7%,P=0.32 for ETV and TDF,respectively);no patient had an eGFR lower than 50 mL/min/1.73 m²or phosphatemia less than 0.48 mmoL/L.In the multivariate analysis,no explanatory variables were identified after adjustment.The cumulative incidence of SPT over 24 mo(25.5%,13.3%,and 52.9%in the naïve,ETV,and TDF groups,respectively)tended to be higher in the TDF group vs the naïve group(hazard ratio:2.283,P=0.05).SPT-free survival at M24 was 57.6%,68.8%,and 23.5%for the naïve,ETV,and TDF groups,respectively.The median surviv

关 键 词：Hepatitis B virus Proximal tubulopathy Biomarkers Renal insufficiency Nucleoside analogues 

分 类 号：R51[医药卫生—内科学]