Factors associated with viral breakthrough in lamivudine monoprophylaxis of hepatitis B virus recurrence after liver transplantation

• Published in: Journal of medical virology 2002-10, Vol.68 (2), p.182-187
• Main Authors: Chan, Henry Lik-Yuen, Chui, Albert Ka-Keung, Lau, Wan-Yee, Chan, Francis Ka-Leung, Wong, May-Ling, Tse, Chi-Hang, Rao, Araga Ramesha Nitin, Wong, John, Sung, Joseph Jao-Yiu
• Format: Article
• Language: English
• Subjects: Adult; Amino Acid Motifs; Amino Acid Sequence; Antiviral Agents - therapeutic use; Base Sequence; Biological and medical sciences; DNA, Viral - blood; DNA, Viral - genetics; Drug Resistance, Viral - genetics; Female; Fundamental and applied biological sciences. Psychology; Genes, Viral; Hepatitis B - complications; Hepatitis B - drug therapy; Hepatitis B - surgery; Hepatitis B - virology; Hepatitis B e Antigens - blood; Hepatitis B virus - drug effects; Hepatitis B virus - genetics; Humans; Lamivudine - therapeutic use; Liver Cirrhosis - drug therapy; Liver Cirrhosis - etiology; Liver Cirrhosis - surgery; Liver Cirrhosis - virology; liver transplantation; Liver Transplantation - adverse effects; Male; Microbiology; Middle Aged; Mutation; polymerase chain reaction; Recurrence; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Virology; YMDD mutant
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.10185

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.