title: Adefovir dipivoxil added to ongoing lamivudine in chronic hepatitis B with YMDD mutant hepatitis B virus.
abstract: OBJECTIVE
  Prolonged lamivudine therapy is associated with treatment-resistant YMDD mutant hepatitis B virus (HBV). We evaluated the efficacy and safety of adding adefovir dipivoxil to lamivudine in 135 patients with chronic hepatitis B (CHB) and YMDD mutant HBV.
  
  
  METHODS
  Ninety-five patients with compensated CHB (group A) were randomized to adefovir 10 mg daily (n = 46) or placebo (n = 49) for 52 weeks while continuing treatment with lamivudine. Forty patients with decompensated hepatitis B or post-liver transplantation (group B) received adefovir and lamivudine. The primary end point was a decline in serum HBV DNA level to 10(5) copies/mL or a >2 log(10) reduction from baseline at weeks 48 and 52.
  
  
  RESULTS
  HBV DNA response occurred in 85% of patients (39 of 46) in group A given combined therapy versus 11% (5 of 46) receiving lamivudine alone (P < 0.001), with a significant change in HBV DNA level from baseline (P < 0.001) between treatment groups (median, -4.6 vs. +0.3 log(10) copies/mL, respectively). Normalization of alanine aminotransferase levels occurred in 31% of patients (14 of 45) receiving combined therapy versus 6% (3 of 48) receiving lamivudine alone (P = 0.002). Ninety-two percent of patients (36 of 39) in group B had an HBV DNA response (median change of -4.6 log(10) copies/mL) and improved liver chemistries (P < or = 0.001). Both treatment regimens were well tolerated, and renal function abnormalities were not observed in either group.
  
  
  CONCLUSIONS
  The addition of adefovir dipivoxil to lamivudine in patients with CHB with compensated or decompensated liver disease due to YMDD mutant HBV is associated with virologic and biochemical improvement during 52 weeks of treatment and is well tolerated.
authors.affiliation: Ochsner Clinic Foundation, New Orleans, LA 70121, USA. rperrillo@ochsner.org
authors.forename: Robert
authors.initials: R
authors.lastname: Perrillo
authors.forename: Hie-Won
authors.initials: HW
authors.lastname: Hann
authors.forename: David
authors.initials: D
authors.lastname: Mutimer
authors.forename: Bernard
authors.initials: B
authors.lastname: Willems
authors.forename: Nancy
authors.initials: N
authors.lastname: Leung
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.forename: Alison
authors.initials: A
authors.lastname: Moorat
authors.forename: Stephen
authors.initials: S
authors.lastname: Gardner
authors.forename: Mary
authors.initials: M
authors.lastname: Woessner
authors.forename: Eric
authors.initials: E
authors.lastname: Bourne
authors.forename: Carol L
authors.initials: CL
authors.lastname: Brosgart
authors.forename: Eugene
authors.initials: E
authors.lastname: Schiff
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D020816:Amino Acid Motifs / Q000235:genetics; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004279:DNA, Viral / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000503:physiopathology / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D014764:Viral Proteins / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D014764:Viral Proteins; D019259:Lamivudine; D000410:Alanine Transaminase; D000225:Adenine; C106812:adefovir dipivoxil