Adefovir Dipivoxil for Wait-Listed and Post–Liver... : Liver Transplantation (original) (raw)

Original Articles: Adefovir for Lamivudine-Resistant CHB

Adefovir Dipivoxil for Wait-Listed and Post–Liver Transplantation Patients with Lamivudine-Resistant Hepatitis B

Final Long-Term Results

Schiff, Eugene1,*,†; Lai, Ching-Lung2; Hadziyannis, Stephanos3; Neuhaus, Peter4; Terrault, Norah5; Colombo, Massimo6; Tillmann, Hans7,‡; Samuel, Didier8; Zeuzem, Stefan9; Villeneuve, Jean-Pierre10; Arterburn, Sarah11; Borroto-Esoda, Katyna11; Brosgart, Carol11; Chuck, Steven11

1_Center for Liver Diseases, University of Miami, Miami, FL_

2_Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong_

3_Department of Medicine and Hepatology, Henry Dunant Hospital, Athens, Greece_

4_Department of Surgery, Charite Campus Virchow, Berlin, Germany_

5_University of California San Francisco, San Francisco, CA_

6_Universita Studi Milano e IRCCS, Ospedale Maggiore, Milano, Italy_

7_Department of Gastroenterology and Hepatology, Medizinische Hochschule Hannover, Hannover, Germany_

8_Centre Hepatobiliaire, Hopital Paul Brousse, Cedex, France_

9_Klinikum der Johann Wolfgang, Goethe Universitaet, Medizinische Klinik II, Frankfurt, Germany_

10_Centre Hospitalier Universitaire de Montreal—Hopital Saint-Luc, Montreal, QC, Canada_

11_Gilead Sciences, Inc., Foster City, CA_

‡Medical Clinic II, University of Leipzig, Leipzig, Germany

*Address reprint requests to University of Miami, Center for Liver Diseases, 1500 NW 12 Ave., Suite 101, Miami, FL 33136

Email: [email protected]

Received 24 May 2006; accepted 11 August 2006

Published online in Wiley InterScience (www.interscience.wiley.com).

†Telephone: 305-243-4615; FAX: 303-243-3877

Abstract

Wait-listed (n = 226) or post–liver transplantation (n = 241) chronic hepatitis B (CHB) patients with lamivudine-resistant hepatitis B virus (HBV) were treated with adefovir dipivoxil for a median of 39 and 99 weeks, respectively. Among wait-listed patients, serum HBV DNA levels became undetectable (<1,000 copies/mL) in 59% and 65% at weeks 48 and 96, respectively. After 48 weeks, alanine aminotransferase (ALT), albumin, bilirubin, and prothrombin time normalized in 77%, 76%, 60%, and 84% of wait-listed patients, respectively. Among posttransplantation patients, serum HBV DNA levels became undetectable in 40% and 65% at weeks 48 and 96, respectively. After 48 weeks, ALT, albumin, bilirubin, and prothrombin time normalized in 51%, 81%, 76%, and 56% of posttransplantation patients, respectively. Among wait-listed patients who underwent on-study liver transplantation, protection from graft reinfection over a median of 35 weeks was similar among patients who did (n = 34) or did not (n = 23) receive hepatitis B immunoglobulin (HBIg). Hepatitis B surface antigen was detected on the first measurement only in 6% and 9% of patients who did or did not receive HBIg, respectively. Serum HBV DNA was detected on consecutive visits in 6% and 0% of patients who did or did not receive HBIg, respectively. Treatment-related adverse events led to discontinuation of adefovir dipivoxil in 4% of patients. Cumulative probabilities of resistance were 0%, 2%, and 2% at weeks 48, 96, and 144, respectively. In conclusion, adefovir dipivoxil is effective and safe in wait-listed or posttransplantation CHB patients with lamivudine-resistant HBV and prevents graft reinfection with or without HBIg. Liver Transpl 13:349-360, 2007. © 2007 AASLD.