Without treatment, the new liver graft typically becomes reinfected with HBV soon after transplantation. Lamivudine plus HBV immune globulin (HBVIG) can prevent reinfection, but HBVIG is expensive and many patients develop resistance to lamivudine.

In Study 435, researchers evaluated a combination of lamivudine plus adefovir in 57 liver transplant patients with lamivudine-resistant HBV. The patients’ median age was 52 years, 88% were male, 77% were Caucasian, and 19% were Asian. All were HBsAg-positive and 42% were HBeAg-positive. Median baseline serum HBV DNA was 4.6 log10 copies/mL and median baseline ALT was 1 x times the upper limit of normal (ULN). Respectively, 43%, 39%, and 18% had Child-Pugh-Turcotte class A, B, and C liver disease.

Before undergoing liver transplants, all patients were taking adefovir with or without lamivudine; adefovir was taken for a median 15 weeks before the transplantation. Over half the patients (n=32; 60%) also received HBVIG.

Results

• After a median 36 weeks post-transplant follow-up, no patient was both HBsAg-positive and had detectable HBV DNA (using a test with a lower limit of 1000 copies/mL).
• Four patients (two receiving and two not receiving HBVIG) had detectable HBsAg at their first post-transplant test; two subsequently had confirmed negative HBsAg and the other two had no additional HBsAg tests.
• Seven patients (four receiving and three not receiving HBVIG) had a single post-transplant HBV DNA measurement greater than 1000 copies/mL; two of the patients receiving HBVIG had subsequent confirmed detectable HBV DNA.
• Four patients (7%) discontinued adefovir due to adverse events; however, only one such event - psychosis - was considered possibly related to adefovir.
• Nine patients (16%) had a maximum post-transplant serum creatinine elevation of grade 2 or higher; this is relevant because adefovir can potentially cause kidney toxicity.
• After a mean 67 weeks of use, no patients developed adefovir resistance.

Conclusion

The researchers concluded that the combination of adefovir plus lamivudine - either with or without HBVIG - started prior to liver transplantation and continued afterward, was “safe and efficacious” in preventing reinfection of the liver graft in patients with lamivudine-resistant HBV. More than 80% of patients never had detectable HBV DNA, and 93% never had detectable HBsAg after transplantation.

View slide presentation http://www.hivandhepatitis.com/2006icr/ddw/pdf/Schiff.pdf

6/2/06

Reference

E. Schiff, C. Lai, P. Neuhaus, and others. Safety and efficacy of adefovir dipivoxil in patients with lamivudine-resistant chronic hepatitis B undergoing liver transplantation. Abstract 480. DDW 2006. May 20-25, 2006. Los Angeles, CA.