POSTLIVER TRANSPLANT ALLOGRAFT REINFECTION WITH A LAMIVUDINE-RESISTANT STRAIN OF HEPATITIS-B VIRUS - LONG-TERM FOLLOW-UP

Lamivudine is a nucleoside analogue with efficacy in the suppression o f hepatitis B viral (HBV) replication. In a previously reported study, lamivudine was administered to patients with chronic, actively replic ating HBV infection who subsequently underwent liver transplantation. Patients became serum HBV DNA-negative in response to lamivudine befor e transplantation, which was continued in the post-transplant period. Two of four patients surviving the immediate postoperative period deve loped allograft reinfection 240 and 409 days post-transplant. The stra in of the reinfecting virus was analyzed, and a mutation in the YMDD r egion of the viral polymerase conferring resistance to Iamivudine was discovered. The long term follow-up of these two patients is reported. The first patient developed ascites 16.5 months after allograft reinf ection. A transjugular liver biopsy performed 18 months after the emer gence of the lamivudine-resistant strain revealed cirrhosis and lobula r hepatitis without rejection. The gradient between hepatic vein wedge d and free pressures was 13 mmHg, consistent with portal hypertension. The second patient, 16 months after allograft reinfection with the la mivudine-resistant strain, is without clinical evidence of portal hype rtension, although liver enzymes remain elevated. Both patients were g iven a trial of famciclovir, which did not significantly suppress HBV viremia. In conclusion, lamivudine-resistant HBV strains with the YMDD mutation may have an aggressive clinical course with rapid progressio n to cirrhosis. Famciclovir did not appear to be an effective rescue a gent in these two patients.