title: Effect of nucleoside and nucleotide analogues on renal function in patients with chronic hepatitis B virus monoinfection.
abstract: OBJECTIVE
  There is controversy regarding whether nucleos(t)ide analogues contribute to renal impairment in patients with chronic hepatitis B virus (HBV) infection. We analyzed changes in renal function in patients with chronic HBV infection and whether these were associated with treatment or comorbidities.
  
  
  METHODS
  We performed a longitudinal observational study to investigate factors associated with renal function in 214 patients (median age, 43 y; 69.2% men) with compensated chronic HBV monoinfection treated with 343 lines of nucleos(t)ide analogues (210 monotherapies, 133 combinations) between 1990 and 2012 (median time, 2.4 y) in France. A linear mixed-effect model was used to model variations of estimated glomerular filtration rate (eGFR, computed with the Chronic Kidney Disease Epidemiology Collaboration formula), adjusting for age, sex, geographic origin, initial liver fibrosis, level of HBV DNA, and an eGFR less than 90 mL/min/1.73 m(2).
  
  
  RESULTS
  The eGFR decreased in patients given adefovir dipivoxil as monotherapy or in a combination (P < .0001 and P < .002, respectively), and remained stable in patients given lamivudine, tenofovir disoproxil fumarate, or entecavir. The eGFR decreased in patients with a baseline eGFR of less than 90 mL/min/1.73 m2, regardless of treatment. The eGFR remained stable or increased, regardless of treatment, in patients with a baseline eGFR of 90 mL/min/1.73 m2 or greater and with an initial HBV DNA level of 100,000 IU/mL or greater. Patients born in areas of high endemicity of HBV were more prone to increases in eGFR with treatment.
  
  
  CONCLUSIONS
  In a real-life study, the eGFR remained stable or increased over time in patients with chronic HBV monoinfection with a baseline eGFR of 90 mL/min/1.73 m2 or higher and treated with tenofovir disoproxil fumarate or entecavir. Patients born in an area of high endemicity of HBV who had initial levels of HBV DNA of 100,000 IU/mL or greater were more likely to have increased eGFR with treatment.
authors.affiliation: Institut Cochin, Université Paris Descartes, Sorbonne Paris Cité, Unité Mixte de Recherche, Paris, France; Centre National de la Recherche Scientifique, Unités Mixtes de Recherche, Paris, France; Institut National de la Santé et de la Recherche Médicale Unité, Paris, France; Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Cochin Saint-Vincent de Paul, Département d'Hépatologie, Paris, France. Electronic address: vincent.mallet@cch.aphp.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Mallet
authors.affiliation: Translational Health Economics Network, Paris, France.
authors.forename: Michaël
authors.initials: M
authors.lastname: Schwarzinger
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Cochin Saint-Vincent de Paul, Département d'Hépatologie, Paris, France.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Vallet-Pichard
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Cochin Saint-Vincent de Paul, Département d'Hépatologie, Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Fontaine
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Cochin Saint-Vincent de Paul, Département d'Hépatologie, Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Corouge
authors.affiliation: Institut Cochin, Université Paris Descartes, Sorbonne Paris Cité, Unité Mixte de Recherche, Paris, France; Centre National de la Recherche Scientifique, Unités Mixtes de Recherche, Paris, France; Institut National de la Santé et de la Recherche Médicale Unité, Paris, France; Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Cochin Saint-Vincent de Paul, Département d'Hépatologie, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Sogni
authors.affiliation: Institut Cochin, Université Paris Descartes, Sorbonne Paris Cité, Unité Mixte de Recherche, Paris, France; Centre National de la Recherche Scientifique, Unités Mixtes de Recherche, Paris, France; Institut National de la Santé et de la Recherche Médicale Unité, Paris, France; Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Cochin Saint-Vincent de Paul, Département d'Hépatologie, Paris, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005602:France; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D000068698:Tenofovir / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; C413685:entecavir; D006147:Guanine; D000068698:Tenofovir
keywords: Antiviral; BeSafe Study; Chronic Kidney Disease; Drug; Mixed Linear Model