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Introduction
A standart therapy for HBV reinfection of the liver allograft does not exist. We evaluated the efficacy and clinical utility of post transplant antiviral combination therapy with lamivudine and ganciclovir in HBV reinfection.
Materials and Methods
Eleven patients (pts) transplanted for HBV cirrhosis, mean age 47±11 years, were included in the study. Immunosuppression was based on cyclosporin, prednisolon and azathioprin. Nine pts had HBV-DNA, HbeAg and HbsAg positive cirrhosis. Five of these 9 pts were treated with famciclovir prior to transplantation. Two pts were HBV-DNA and HbeAg negative, had developed anti-Hbe, but were still HbsAg positive. These pts had no antiviral treatment before OLT. For prevention of HBVgraft reinfection all pts received 10000 IU anti-Hbs immunglobuline (anti-Hbs Ig) during the anhepatic phase, 1000 IU anti-Hbs/day for the first 10 postoperative days and passive immunoprophylaxis for 2 years. Seven pts received addionally 3x 500 mg famciclovir/day to prevent reinfection.
Reinfection, assessed by detection of HBV-DNA level in serum, occured at a mean of 15 months (ranges 2,5-48 months) and was severe (HBV-DNA level > 10000 pg/ml) in 5 pts, moderate (HBV-DNA level 1000-10000 pg/ml) in 3 pts and mild (HBV-DNA level < 1000 pg/ml) in 3 pts. Reinfection was associated with dysfunction and elevated liver biochemistries.
Results
Five pts with severe reinfection received ganciclovir i.v. (10 mg/kg/day), 6 pts received ganciclovir p.o.(3x750 mg /day/for pts < 75 kg ; 3x1g/day/for pts > 75 kg body weight). All pts received lamivudine p.o. (150 mg/twice a day). After 150 days of treatment all pts had a complete loss of HBV-DNA from serum, became HbsAg and HbeAg negative, had developed anti-Hbe and had a normalization of the liver biochemistry. The therapy was at least continued for 8 months, was well tolerated by all pts and no serious side effects occured. At a median follow up of 17 months all pts remained HBV-DNA negative. Resistant strains of HBV against the therapeutic regime did not develop. All pts were continued on oral ganciclovir after elimination of HBV-DNA. The antiviral therapy was stopped in 5 pts, who had developed an anti-Hbs titer > 1000 U/l after readministration of anti-Hbs Ig.
Conclusion
The combination of lamivudine and ganciclovir is an effective treatment of recurrent HBV infection after OLT. The combination of two antiviral drugs decreases the development of resistant HBV strains. A complete eradication of HBV is unlikely but til now under anti-Hbs administration there was no relaps of viral infection even after treatment was stopped.