title: Factors associated with viral breakthrough in lamivudine monoprophylaxis of hepatitis B virus recurrence after 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.
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong. hlychan@hotmail.com
authors.forename: Henry Lik-Yuen
authors.initials: HL
authors.lastname: Chan
authors.forename: Albert Ka-Keung
authors.initials: AK
authors.lastname: Chui
authors.forename: Wan-Yee
authors.initials: WY
authors.lastname: Lau
authors.forename: Francis Ka-Leung
authors.initials: FK
authors.lastname: Chan
authors.forename: May-Ling
authors.initials: ML
authors.lastname: Wong
authors.forename: Chi-Hang
authors.initials: CH
authors.lastname: Tse
authors.forename: Araga Ramesha Nitin
authors.initials: AR
authors.lastname: Rao
authors.forename: John
authors.initials: J
authors.lastname: Wong
authors.forename: Joseph Jao-Yiu
authors.initials: JJ
authors.lastname: Sung
mesh_terms: D000328:Adult; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use*; D001483:Base Sequence; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005814:Genes, Viral; D006509:Hepatitis B / Q000150:complications / Q000188:drug therapy* / Q000601:surgery* / Q000821:virology; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000209:etiology / Q000601:surgery / Q000821:virology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012008:Recurrence
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D019259:Lamivudine