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 preliver 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.
Peters
M G
MG
University of California at San Francisco, 94143, USA. mpeters@itsa.ucsf.edu
Singer
G
G
Howard
T
T
Jacobsmeyer
S
S
Xiong
X
X
Gibbs
C S
CS
Lamy
P
P
Murray
A
A
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D002353:Carrier State; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D006515:Hepatitis B virus / Q000201:enzymology; D006801:Humans; D007116:Immunization, Passive; D016030:Kidney Transplantation; D019259:Lamivudine / Q000627:therapeutic use*; D017093:Liver Failure / Q000601:surgery / Q000821:virology*; D016031:Liver Transplantation; D009154:Mutation / Q000235:genetics; D063065:Organophosphonates
D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; D004259:DNA-Directed DNA Polymerase; D000225:Adenine; C106812:adefovir dipivoxil