Adefovir dipivoxil therapy for lamivudine-resistant hepatitis B in pre- and post-liver transplantation patients.
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.
Schiff
Eugene R
ER
Center for Liver Diseases, University of Miami, Miami, FL 33136, USA. Eschiff@med.miami.edu
Lai
Ching-Lung
CL
Hadziyannis
Stefanos
S
Neuhaus
Peter
P
Terrault
Norah
N
Colombo
Massimo
M
Tillmann
Hans L
HL
Samuel
Didier
D
Zeuzem
Stefan
S
Lilly
Leslie
L
Rendina
Maria
M
Villeneuve
Jean-Pierre
JP
Lama
Nicole
N
James
Craig
C
Wulfsohn
Michael S
MS
Namini
Hamid
H
Westland
Christopher
C
Xiong
Shelly
S
Choy
Gavin S
GS
Van Doren
Sally
S
Fry
John
J
Brosgart
Carol L
CL
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
D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; D000225:Adenine; C106812:adefovir dipivoxil