A randomized study of adefovir dipivoxil in place of HBIG... : Hepatology (original) (raw)
Viral Hepatitis
A randomized study of adefovir dipivoxil in place of HBIG in combination with lamivudine as post–liver transplantation hepatitis B prophylaxis
Angus, Peter W.1*; Patterson, Scott J.1; Strasser, Simone I.2; McCaughan, Geoffrey W.3; Gane, Edward4
1_Victorian Liver Transplant Unit, Austin Health, Victoria, Australia_
2_AW Morrow Gastroenterology and Liver Center, Royal Prince Alfred Hospital, New South Wales, Australia_
3_AW Morrow Gastroenterology and Liver Center, Centenary Research Institute, Australian Liver Transplant Unit, Royal Prince Alfred Hospital, University of Sydney, New South Wales, Australia_
4_New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand_
* Address reprint requests to: Liver Transplant Unit, Austin Health, Studley Road, Heidelberg, VIC 3084, Australia
Email:[email protected]
Received 22 April 2008; Accepted 6 July 2008
Published online in Wiley InterScience (www.interscience.wiley.com).
Supported by Gilead Sciences donated drug and provided unrestricted research support for this study.
Potential conflict of interest: Dr. Angus advises and received grants from Gilead. Dr. Strasser advises and is on the speakers' bureau of Gilead. Dr. McCaughan advises Gilead.
Peter Angus, Geoffrey McCaughan, and Simone Strasser received minor honoraria from Gilead Sciences for participation in Advisory Boards or Speakers' Bureau.
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Abstract
Prior to effective prophylaxis, liver transplantation for hepatitis B virus (HBV)-related disease was frequently complicated by recurrence, which could be severe and rapidly progressive. Combination hepatitis B immunoglobulin (HBIG) and lamivudine prophylaxis reduces this rate of recurrence to <5% at 5 years; however, HBIG administration is costly and inconvenient. We conducted a multicenter randomized study of adefovir dipivoxil substitution for low-dose intramuscular (IM) HBIG in patients without HBV recurrence at least 12 months posttransplantation for HBV-related disease. Thirty-four patients were randomized, 16 to adefovir (1 patient withdrew consent at 3 months and is not considered in the results) and 18 to continue HBIG. All continued lamivudine. Groups were well matched by age, sex, and time since transplantation (median, 4.5 years), and background virological risk for HBV recurrence (30% of patients in the adefovir group, 24% in the HBIG group having detectable HBV DNA at transplantation). All patients were alive at study completion without recurrence. One patient in the adefovir group became hepatitis B surface antigen–positive at 5 months but was persistently HBV DNA undetectable via polymerase chain reaction (sensitivity 14 IU/mL) over the following 20 months. Median creatinine was not significantly changed over the course of the study in either group. One patient in the adefovir group with a background of diabetic and hypertensive nephropathy (baseline creatinine 150 μmol/L) developed increased creatinine leading to dose reduction and ultimately cessation of adefovir at 15 months. Yearly cost of combination adefovir/lamivudine prophylaxis was 8,290versus8,290 versus 8,290versus13,718 IM HBIG/lamivudine. Conclusion: Compared with combination HBIG plus lamivudine prophylaxis, combination adefovir plus lamivudine provides equivalent protection against recurrent HBV infection but with better tolerability and less cost. (Hepatology 2008.)
Abbreviations: ADV/LAM, adefovir dipivoxil and lamivudine; HBIG, hepatitis B immunoglobulin; HBIG/LAM, HBIG and lamivudine; HBsAb, hepatitis B surface antibody; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; IM, intramuscular; IV, intravenous; PCR, polymerase chain reaction.
Copyright © 2008 American Association for the Study of Liver Diseases.