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Keywords:

  • polymerase chain reaction;
  • YMDD mutant;
  • liver transplantation

Abstract

This study aimed to investigate the factors associated with viral breakthrough among liver transplant recipients who receive lamivudine monoprophylaxis. Consecutive patients receiving liver transplantation for HBV-related liver disease from June 1999 to October 2000 were studied. All patients received lamivudine 100 mg daily pre- and post-transplant. Serum samples were collected before lamivudine treatment, before liver transplantation, and then every 3–6 months after liver transplantation. Lamivudine-resistant mutations at the YMDD motif of HBV P gene were detected by direct sequencing and HBV DNA was quantified by real-time polymerase chain reaction (PCR). Ten patients, 7 males and 3 females, aged 50.5 ± 7.9 years, were studied. Three patients had fulminant hepatitis and 7 patients had end-stage cirrhosis before liver transplantation. Lamivudine was started at 4.5 (range 0–40) weeks before liver transplantation. The median post-transplant follow-up was 16 (range 12–23) months. Four patients developed YMDD mutations 10.5 (0–16) months after transplantation with relapse of viraemia (median 1,294, range 51–3,135 MEq/ml). All patients who developed YMDD mutants had end-stage liver cirrhosis, and HBV DNA were detectable on the day of liver transplantation (median 0.62, range 0.086–1.63 MEq/ml). On the contrary, all 3 patients transplanted for fulminant hepatitis did not have YMDD mutation. Among the 3 end-stage cirrhotic patients who had negative HBV DNA before liver transplantation, none developed YMDD mutation. In conclusion, patients transplanted for fulminant hepatitis B and cirrhotic patients in whom HBV DNA could be rendered PCR negative before liver transplantation are unlikely to develop YMDD mutation on lamivudine monoprophylaxis. J. Med. Virol. 68:182–187, 2002. © 2002 Wiley-Liss, Inc.