Long-term therapy with lamivudine in renal transplant recipients with chronic hepatitis B.
BACKGROUND
Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication. As other available HBV therapies, its efficacy is hampered by relapse after discontinuation and by the risk of viral breakthrough. A recent study suggests that pre-emptive lamivudine therapy improves survival in HBV renal transplants, but few data are available regarding its long-term use in this population. The clinical features, course and viral mutations associated with the emergence of viral resistance in this population have not been well studied.


METHODS
We followed 14 consecutive renal transplant patients treated with lamivudine for chronic hepatitis B. Breakthrough was defined as the reappearance of HBV DNA by hybridization. In patients with breakthrough, lamivudine was always continued and patients were followed up monthly. Mutations associated with viral resistance were determined by sequencing the polymerase encoding gene at the beginning of treatment and at the time of breakthrough.


RESULTS
The median duration of treatment was 64.5 months. Resistance to lamivudine appeared in eight patients (57%) after a median duration of treatment of 15 (9-24) months. During a 51 month follow-up after breakthrough, only three of eight patients had a flare-up with alanine aminotransferase levels more than 5 ULN, and no hepatic decompensation was observed. Analysis of HBV sequencing after breakthrough revealed specific resistance mutations in both the B and C domains of the polymerase (rtL180M/M204V, n = 5; rtM204I, n = 2).


CONCLUSIONS
Lamivudine is a safe and effective treatment of active hepatitis B in renal transplant patients. Resistance to treatment is frequent but seems to have little clinical impact over the considered period. In our experience, the YMDD mutation accounts for most cases of virological escape in patients with good compliance.
Thabut
Dominique
D
Hepato-gastroenterology Unit, Hôpital Pitié-Salpêtrière, Paris, France. dthabut@libertysurf.fr
Thibault
Vincent
V
Bernard-Chabert
Brigitte
B
Mouquet
Catherine
C
Di Martino
Vincent
V
Le Calvez
Sophie
S
Opolon
Pierre
P
Benhamou
Yves
Y
Bitker
Marc Olivier
MO
Poynard
Thierry
T
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000595:Amino Acid Sequence; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D005260:Female; D005814:Genes, Viral / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D016030:Kidney Transplantation; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008134:Long-Term Care / Q000379:methods; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*
D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000410:Alanine Transaminase