Adefovir Dipivoxil Provides Effective Prophylaxis Against Hepatitis B Virus Graft Re-infection With Or Without Immune Globulin Therapy

Main Category: Liver Disease / Hepatitis
Also Included In: Clinical Trials / Drug Trials
Article Date: 28 Apr 2006 - 0:00 PDT

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New results document the safety and efficacy of the nucleotide analogue adefovir dipivoxil (ADV, HepseraR) for the prevention of graft re-infection in patients with lamivudine-resistant chronic hepatitis B undergoing orthotopic liver transplantation.

The data, presented at the 41st Annual Meeting of the European Association for the Study of the Liver (EASL), show that ADV reduced the rate of re-infection regardless of whether patients were receiving concurrent hepatitis B immune globulin (HBIg) therapy.

"Adefovir satisfies an unmet need of managing lamivudine resistance and thus represents an important treatment for patients before and after transplantation with lamivudine-resistant disease who are at increased risk of morbidity and mortality," said Eugene R. Schiff, MD, professor of medicine and chief of the hepatology division at the University of Miami School of Medicine in Miami, Florida.

Dr. Schiff reported the results of 36 weeks follow-up post-transplantation in 57 patients who were treated with ADV, 10 mg/d, added to ongoing lamivudine, 100 mg/d both before and after their transplant operation.

The analysis is the extension arm of Study 435, which was an international, compassionate use trial of the safety and efficacy of ADV for the treatment of 226 wait-listed and 241 post-transplantation patients with lamivudine-resistant chronic hepatitis B.

"Hepatitis B immune globulin is effective prophylaxis for graft re-infection however it is expensive and requires parenteral administration and escape mutations can arise," Dr. Schiff pointed out.

Lamivudine is effective in lowering viral titers both before and after transplantation and is effective prophylaxis for graft re-infection, however frequent development of resistance is an important limitation.

Interferon alpha is associated with the risk of serious adverse patients in patients with decompensated cirrhosis and with the risk of graft rejection post-transplantation, he added.

Thirty four of the 57 patients in the present analysis also received hepatitis B immune globulin.

Re-infection was defined a priori as confirmed detection of hepatitis B surface antigen (HBsAg) or hepatitis B virus DNA in serum.

Results showed that over 80% of patients never had detectable hepatitis B virus DNA at the time of follow-up, and 93% never had detectable hepatitis B surface antigen (HBsAg).

ADV treatment was safe and generally well tolerated.

No patient who underwent on-study liver transplantation developed resistance over a mean of 67 weeks of ADV treatment.

"The take-home message is that 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 study was supported by Gilead Sciences in Foster City, California.

Jill Stein is a Paris-based freelance medical writer.

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