title: Long-term adefovir plus lamivudine therapy does not decrease creatinine clearance in HBeAg-negative chronic hepatitis B patients.
abstract: OBJECTIVE
  As there are concerns about potential nephrotoxicity of nucleotide analogues, we evaluated renal function parameters during long-term adefovir and lamivudine combination therapy.
  
  
  METHODS
  Forty-six HBeAg-negative patients with lamivudine-resistance treated with adefovir and lamivudine for up to 90 months were included. Renal function was assessed by estimated creatinine clearance (eC(CR) ) and compared with a matched control group of untreated inactive hepatitis B virus carriers.
  
  
  RESULTS
  Serum HBV DNA became undetectable in 39 (85%) patients after a mean of 37 ± 21 months. Three (6.5%) patients developed virological breakthrough. Adefovir resistance was detected in two patients. At the end of follow up, there was a significant decrease in mean eC(CR) (95 ± 31-83 ± 30 ml/min, P = 0.003) in the treated patients with 16% presenting aeC(CR) decrease >30%. Similar changes in eC(CR) were observed in the control group (108 ± 28-96 ± 26 ml/min, P = 0.003). In multiple regression analysis, age and baseline eC(CR) were independent predictors of eC(CR) reduction.
  
  
  CONCLUSIONS
  Adefovir and lamivudine combination therapy is not an independent factor for significant renal dysfunction in HBeAg-negative patients with lamivudine-resistance. Baseline age and creatinine clearance are the only independent predictors of worsening renal function.
authors.affiliation: 2nd Academic Department of Internal Medicine, Hippokration Hospital of Athens, Athens, Greece. smanolak@med.uoa.gr
authors.forename: Spilios
authors.initials: S
authors.lastname: Manolakopoulos
authors.forename: Athanasia
authors.initials: A
authors.lastname: Striki
authors.forename: Melanie
authors.initials: M
authors.lastname: Deutsch
authors.forename: Maria
authors.initials: M
authors.lastname: Mela
authors.forename: Ioannis
authors.initials: I
authors.lastname: Ketikoglou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tzourmakliotis
authors.forename: Emanuel K
authors.initials: EK
authors.lastname: Manesis
authors.forename: George V
authors.initials: GV
authors.lastname: Papatheodoridis
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000367:Age Factors; D000368:Aged; D003401:Creatine / Q000378:metabolism*; D024882:Drug Resistance, Viral / Q000502:physiology; D004359:Drug Therapy, Combination; D005260:Female; D006115:Greece; D006509:Hepatitis B / Q000188:drug therapy*; D006513:Hepatitis B e Antigens / Q000097:blood; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D019259:Lamivudine / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*
chemical_list: D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000225:Adenine; D003401:Creatine