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

Paul Carrier 1, 2 Marilyne Debette-Gratien 1, 2 Anais Labrunie 3, 4 Sophie Alain 5 Marianne Maynard 6 Nathalie Ganne-Carrie 7 Eric Nguyen-Khac 8 Pauline Pinet 9 Victor de Ledinghen 10 Christophe Renou 11 Philippe Mathurin 12 Claire Vanlemmens 13 Vincent Di Martino 13 Anne Gervais 14 Juliette Foucher 15 Fouchard-Hubert Isabelle 10 Julien Vergniol 16 Isabelle Hourmand-Ollivier 17 Daniel Cohen 18, 19 Xavier Duval 20, 21 Thierry Poynard 22 Marc Bardou 23 Armand Abergel 24 Manh-Thong Dao 25 Thierry Thevenot 26 Jean-Baptiste Hiriart 27 Valerie Canva 28 Guillaume Lassailly 29 Christine Aurieres 30 Nathalie Boyer 31, 32, 33 Dominique Thabut 34 Pierre-Henri Bernard 35 Matthieu Schnee 36 Dominique Larrey 37, 38 Bertrand Hanslik 39 Severine Hommel 40 Jeremie Jacques 1 Veronique Loustaud-Ratti 41 Anais Brayette 1 Marie Essig 42, 43
Abstract : 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: Naive, 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 naive, 28 starting ETV, and 26 starting TDF) had no SPT at inclusion. At M24, the prevalence of SPT was not statistically different between naive 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 m(2) or 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 naive, ETV, and TDF groups, respectively) tended to be higher in the TDF group vs the naive group (hazard ratio: 2.283, P = 0.05). SPT-free survival at M24 was 57.6%, 68.8%, and 23.5% for the naive, ETV, and TDF groups, respectively. The median survival time without SPT, evaluated only in the TDF group, was 5.9 mo. CONCLUSION The prevalence and incidence of SPT was higher in TDF-treated patients compared to naive patients. SPT in the naive population suggests that HBV can induce renal tubular toxicity.
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Soumis le : lundi 28 février 2022 - 11:11:02
Dernière modification le : jeudi 12 mai 2022 - 08:04:03

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Paul Carrier, Marilyne Debette-Gratien, Anais Labrunie, Sophie Alain, Marianne Maynard, et al.. Subclinical proximal tubulopathy in hepatitis B: The roles of nucleot(s)ide analogue treatment and the hepatitis B virus. WORLD JOURNAL OF HEPATOLOGY, 2020, 12 (12), pp.1326-1340. ⟨10.4254/wjh.v12.i12.1326⟩. ⟨hal-03590856⟩

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