Promising Results in Phase II Study of Treatment with Pegasys in HBEAG Positiv

liver411

Adefovir Effective in Post-Transplant Patients Failing Lamivudine



By Brian Boyle, MD



Resistance is a significant problem with prolonged Epivir-HBV (lamivudine) treatment for chronic hepatitis B virus (HBV) infection. Adefovir dipivoxil (ADV) has been shown to have potent activity against wild-type and Epivir-HBV resistant HBV.



In a study presented at the 52nd AASLD Meeting the safety and efficacy of adding ADV 10 mg once daily to existing HBV therapy (Epivir-HBV, HBIG, famciclovir, or ganciclovir) was evaluated in an open-label study of 127 post-liver transplant patients with clinical evidence of Epivir-HBV failure. All patients were HBsAg and HBV DNA positive at baseline.



After 48 weeks of ADV therapy, the median changes in the study patients were an HBV DNA reduction of 4.2 log10 copies/mL, an ALT reduction of 58.7 U/L, an albumin increase of 0.6 g/dL, and a bilirubin reduction of 1.5 mg/dl. Prothrombin time was not changed.



ADV appeared to be well tolerated in the majority of these patients. The most common adverse events reported were asthenia (20%), headache (12%), pharyngitis (11%) and abdominal pain (10%). Eighteen patients experienced an increase in serum creatinine of ³ 0.5 mg/dL from baseline. Five patients had resolution of these elevations without sequelae, while 13 (12 of whom were also being treated concurrently with cyclosporine and/or tacrolimus) had pre-existing renal insufficiency at baseline and experienced further increases in serum creatinine. There were 10 deaths in the study, but 9 of these deaths were prior to the patient commencing ADV and 1 patient died from underlying HBV disease after 13 months on study. Finally, 4 patients permanently discontinued study drug, 2 of which were due to an adverse event.



The authors conclude, "ADV 10 mg, when added to LAM in post-liver transplant patients who have failed LAM therapy, results in significant antiviral efficacy [and] is not associated with treatment limiting toxicity in the majority of patients."



11/13/01