Adefovir Dipivoxil有助肝脏移植病患避免再度感染B肝

Adefovir Dipivoxil May Block Hepatitis B Reinfection in Liver Transplant Patients
By
Medscape Medical News
May 10, 2006 (Vienna) — Early results suggest that adefovir dipivoxil may help block reinfection with the hepatitis B virus (HBV) among infected patients who are resistant to lamivudine and undergo liver transplantation. While these findings are encouraging, an expert warns that long-term follow-up is required to confirm the drug's benefits.

According to Jean-Michel Pawlotsky, MD, PhD, "The principal danger of liver transplantation for HBV infection is HBV recurrence, which may be particularly severe in this context. It is well prevented by the use of hepatitis B immunoglobulins (HBIg), and even [more so] when HBIg are used in combination with specific antivirals such as lamivudine. However, [lamivudine therapy is not helpful] if the patients are already lamivudine resistant."

This new study demonstrates that "using lamivudine plus adefovir in combination in lamivudine-resistant patients prior to and after transplantation prevented HBV infection recurrence in the vast majority of patients, with or without HBIg (ie, it protected the liver graft against HBV)," Dr. Pawlotsky told Medscape via email. He was not involved in the research but was a moderator at the session where it was presented here by Eugene Schiff, MD, from the University of Miami, Florida, at the 41st annual meeting of the European Association for the Study of the Liver (EASL). Dr. Pawlotsky is director of the French National Reference Center for Viral Hepatitis B, C, and delta, Department of Virology and of the INSERM Research Unit U635 at Henri Mondor Hospital, University of Paris 12, in Creteil, France. He is also an advisor for Gilead, the manufacturer of adefovir.

Dr. Schiff and colleagues gave adefovir to 57 patients who had lamivudine-resistant chronic HBV infection and required liver transplantation. Patients received the agent for a median of 15 weeks prior to transplantation and a median of 36 weeks after transplantation. Those initially receiving lamivudine remained on the drug. In addition, 60% of patients received HBIg.

At baseline, all patients were hepatitis B surface antigen (HBsAg)–positive, and 42% were hepatitis B e antigen (HbeAg)–positive. Patients' median serum HBV DNA was 4.6 log10 copies/mL, and their median alanine transaminase (ALT) level was 1.0 X ULN.

After transplantation, none of the patients were both HBsAg-positive and HBV DNA positive. Four patients, 2 of whom received HBIg, had HBsAg detected in their first posttransplantation test. Of these, 2 eventually became HBsAg-negative with subsequent testing, and 2 patients had no additional HBsAg follow-up.

Of the patients who received HBIg, 13% had a single HBV DNA measurement greater than the lower limit of quantification (LLQ). Similarly, among those who did not receive HBIg, 12% had a single HBV DNA measurement over LLQ.

None of the patients developed resistance to adefovir during a mean of 67 weeks on the study drug. Cumulative probabilities of the development of resistance were 2% at weeks 96 and 144.

In general, adefovir was well tolerated. Four patients (7%) discontinued the agent due to adverse events. Of the patients also receiving nephrotoxic immunosuppressant drugs, 84% had normal serum creatinine levels or only grade 1 elevations.

"Adefovir dipivoxil appears to be effective prophylaxis for HBV graft reinfection with or without HBIg," the authors conclude in their abstract. They also reported that the drug is "safe and generally well-tolerated in liver transplantation patients."

Dr. Pawlotsky told Medscape that the study does demonstrate a benefit for using adefovir among lamivudine-resistant patients in this clinical context. The trial, however, is limited by its small sample size, even though a sample of 57 is relatively large for a transplantation study.

In addition, Dr. Pawlotsky said, follow-up of several years is required to truly determine if HBV infection has actually been prevented, whether some patients will experience reinfections, and whether these reinfections are related to resistance, poor adherence, or other causes. He believes that future research should concentrate on use of potent antiviral drugs with good resistance profiles.

EASL 2006: Abstract 2. Presented April 27, 2006.