title: Adefovir dipivoxil therapy for lamivudine-resistant hepatitis B in pre- and post-liver transplantation patients.
abstract: Three-hundred and twenty-four patients were enrolled in an open-label, multicenter, international study in which pre- and post-liver transplantation (LT) patients with recurrent chronic hepatitis B (CHB) and evidence of lamivudine-resistant HBV were treated with adefovir dipivoxil 10 mg once daily. In the pre- and post-LT cohorts, 128 and 196 patients were treated for a median duration of 18.7 and 56.1 weeks, respectively. In patients who received 48 weeks of treatment, 81% of the pre-LT and 34% of the post-LT cohort achieved undetectable serum hepatitis B virus (HBV) DNA (Roche Amplicor Monitor polymerase chain reaction [PCR] assay lower limit of quantification [LLQ] < 400 copies/mL) with a median change in serum HBV DNA from baseline of -4.1 log(10) and -4.3 log(10) copies/mL, respectively. Serum alanine aminotransferase (ALT), albumin, bilirubin, and prothrombin time normalized in 76%, 81%, 50%, and 83% of pre-LT patients and 49%, 76%, 75%, and 20% of post-LT patients. The Child-Pugh-Turcotte (CPT) score improved in over 90% of patients in both cohorts. Genotypic analysis of 122 HBV baseline samples revealed that 98% of these patients had lamivudine-resistant mutant HBV. No adefovir resistance mutations were identified in patients after 48 weeks of therapy. One-year survival was 84% for pre-LT and 93% for post-LT patients (Kaplan-Meier analysis). Treatment-related adverse effects associated with adefovir dipivoxil in this setting were primarily mild to moderate in severity. In conclusion, 48 weeks of adefovir dipivoxil resulted in significant improvements in virologic, biochemical, and clinical parameters in CHB patients pre- and post-LT with lamivudine-resistant HBV.
authors.affiliation: Center for Liver Diseases, University of Miami, Miami, FL 33136, USA. Eschiff@med.miami.edu
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Schiff
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Lai
authors.forename: Stefanos
authors.initials: S
authors.lastname: Hadziyannis
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
authors.forename: Norah
authors.initials: N
authors.lastname: Terrault
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
authors.forename: Hans L
authors.initials: HL
authors.lastname: Tillmann
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Leslie
authors.initials: L
authors.lastname: Lilly
authors.forename: Maria
authors.initials: M
authors.lastname: Rendina
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Villeneuve
authors.forename: Nicole
authors.initials: N
authors.lastname: Lama
authors.forename: Craig
authors.initials: C
authors.lastname: James
authors.forename: Michael S
authors.initials: MS
authors.lastname: Wulfsohn
authors.forename: Hamid
authors.initials: H
authors.lastname: Namini
authors.forename: Christopher
authors.initials: C
authors.lastname: Westland
authors.forename: Shelly
authors.initials: S
authors.lastname: Xiong
authors.forename: Gavin S
authors.initials: GS
authors.lastname: Choy
authors.forename: Sally
authors.initials: S
authors.lastname: Van Doren
authors.forename: John
authors.initials: J
authors.lastname: Fry
authors.forename: Carol L
authors.initials: CL
authors.lastname: Brosgart
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007668:Kidney / Q000187:drug effects; D019259:Lamivudine / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; D000225:Adenine; C106812:adefovir dipivoxil