Outcome of lamivudine resistant hepatitis B virus mutant post-liver transplantation on lamivudine monoprophylaxis.
BACKGROUND
We aimed to investigate the clinical outcome of patients who develop lamivudine resistant hepatitis B virus mutants (YMDD mutants) after liver transplantation.


METHODS
Patients who received liver transplantation for hepatitis B-related liver diseases from 1999 to 2002 were studied. All patients received lamivudine monotherapy before and after liver transplantation. HBsAg and HBV DNA were regularly monitored, and YMDD mutation was detected by direct sequencing.


RESULTS
Twenty patients were followed up for median 94 wk (range: 15-177 wk) post-liver transplantation. Six patients developed YMDD mutants, and the cumulative probability of developing YMDD mutations post-liver transplantation was 21% in 1 yr and 34% in 2 yr. One patient developed YMDD mutants before liver transplantation and died of hepatitis reactivation and liver failure 15 wk post-transplantation. The other five patients developed YMDD mutants 32-72 wk after liver transplantation. Two of them developed severe hepatitis which responded promptly to adefovir dipivoxil. The remaining three patients with YMDD mutants had minimal to mild hepatitis. The cumulative survival for patients with YMDD mutants was 83% and 28% at 1 and 2 yr, respectively. Only one patient who did not develop YMDD mutants died at week 119 due to chronic rejection. The post-transplant survival for patients with YMDD mutants was significantly poorer than those without YMDD mutants (log rank test p = 0.083).


CONCLUSIONS
The emergence of YMDD mutants after liver transplantation on lamivudine monoprophylaxis had wide range of clinical presentations and was associated with increased mortality.
Chan
Henry Lik-Yuen
HL
Department of Medicine & Therapeutics, Chinese University of Hong Kong, Hong Kong SAR, China. hlchan@cuhk.edu.hk
Chui
Albert Ka-Keung
AK
Lau
Wan-Yee
WY
Chan
Francis Ka-Leung
FK
Hui
Alex Yui
AY
Rao
Araga Ramesha Nitin
AR
Wong
John
J
Lai
Eric Chun-Hung
EC
Sung
Joseph Jao-Yiu
JJ
D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018890:Chemoprevention / Q000379:methods; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery* / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D016896:Treatment Outcome
D000998:Antiviral Agents; D019259:Lamivudine