Fulminant hepatic failure resulting from lamivudine-resistant hepatitis B virus in a renal transplant recipient - Durable response after orthotopic liver transplantation on adefovir dipivoxil and hepatitis B immune globulin

Background. Mutations in the hepatitis B virus (HBV) genome may occur during therapy. Methods. We report an asymptomatic HBV carrier who underwent transplantation for end-stage renal disease. She developed an HBV flare 6 months after transplantation and was placed on lamivudine, After initial rapid improvement, she relapsed clinically and virologically. She decompensated with jaundice, peripheral edema, ascites, encephalopathy, coagulopathy, and hepatorenal syndrome. A liver biopsy specimen revealed submassive necrosis. Results, Emergency liver transplantation was performed: lamivudine was discontinued. Hepatitis B immunoglobulin and adefovir dipivoxil were initiated. Sixteen months after orthotopic liver transplantation, she is HBV DNA seronegative with normal liver enzymes. Sequencing of HBV polymerase gene from pre-liver transplantation sera did not detect the usual lamivudine resistance mutations in the YMDD motif but instead two other mutations (F514-->L, L528-->M). Lamivudine resistance was demonstrated in vitro. Conclusions. Asymptomatic HBV carriers may reactivate following renal transplantation after immunosuppression. Resistance to lamivudine may result in severe hepatic damage in immunocompromised patients.