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Adefovir Dipivoxil Thwarts Recurrent Hepatitis B Virus Graft Infection With or Without Hepatitis B Immune Globulin Therapy: Presented at EASL

By Jill Stein

VIENNA, AUSTRIA -- April 27, 2006 -- The combination of adefovir dipivoxil (ADV, Hepsera^R) and lamivudine started before liver transplantation and continued afterwards safely prevents graft re-infection in patients with lamivudine-resistant chronic hepatitis B either with or without concurrent hepatitis B immune globulin therapy, researchers reported at the 41^st Annual Meeting of the European Association for the Study of the Liver (EASL).

ADV is the first nucleotide analogue available for the treatment of chronic hepatitis B.

Eugene Schiff, MD, professor of medicine and chief, hepatology division, University of Miami School of Medicine in Miami, Florida, United States, presented the results of a long-term follow-up in 57 patients who were treated with ADV 10 mg/day added to ongoing lamivudine 100 mg/day both before and after liver transplantation.

All subjects were enrolled in Study 435, which tested the safety and efficacy of ADV for the treatment of wait-listed and post-transplantation patients with lamivudine-resistant chronic hepatitis B.

"Our findings are extremely important because re-infection not only reduces graft survival but also accelerates disease progression and has been associated with death in the first 12 months after transplantation," Dr. Schiff said on April 26^th.

Thirty four patients in the present analysis also received hepatitis B immune globulin.

Results show that over 80% of patients never had detectable hepatitis B virus DNA at a mean post-transplantation follow-up of 36 weeks, and 93% never had detectable hepatitis B surface antigen (HBsAg).

ADV treatment was safe and generally well tolerated. Four (7%) patients stopped ADV because of an adverse event, however, none was judged to be due to ADV treatment.

No patient who underwent on-study liver transplantation developed resistance over a mean of 67 weeks of ADV treatment. The cumulative probabilities of resistance were 0% at 48 weeks, 2% at 96 weeks, and 2% at 144 weeks.

"The take-home message is that most patients who received ADV plus lamivudine both before and after liver transplantation showed no evidence of re-infection with the hepatitis B virus, whether or not they were taking concurrent hepatitis B immunoglobulin," Dr. Schiff said.

The pre- and post-transplantation treatment of chronic hepatitis B has been a major clinical challenge, he added. Interferon-based treatments prior to transplantation have been associated with serious adverse effects in patients with decompensated cirrhosis and are contraindicated after transplant because they increase the risk of graft injection.

Hepatitis B immune globulins, which are frequently used with antivirals as prophylaxis against recurrent hepatitis B virus in post-transplant patients, require parenteral administration and are too expensive for widespread use, he explained.

Genotypic hepatitis B virus lamivudine resistance can be found in up to 70% of hepatitis B virus-infected individuals treated with lamivudine for up to 4 years, Dr. Schiff said. These patients can develop a lamivudine-resistant hepatitis B virus strain that is potentially transmissible to hepatitis B virus-vaccinated individuals.

More than 400 million people are chronic hepatitis B carriers worldwide. Approximately 1.25 million people are affected in the U.S.

The study was supported by Gilead Sciences in Foster City, California.


[Presentation title: Safety and Efficacy of Adefovir Dipivoxil in Patients with Lamivudine-Resistant Chronic Hepatitis B Undergoing Liver Transplantation. Abstract 2.]

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