Efficacy of lamivudine re-treatment in a patient with hepatitis B virus (HBV) recurrence after liver transplantation and HBV-DNA breakthrough during the first treatment.
BACKGROUND
Transplantation for terminal hepatitis B virus (HBV) disease is aggravated by a high rate of reinfection and disease recurrence. Lamivudine, a new nucleoside analog, is a potent inhibitor of HBV synthesis, but its use may lead to the emergence of HBV-DNA polymerase mutants resistant to the drug.


RESULTS
We describe the case of a patient who developed an HBV recurrence after liver transplantation and was treated with lamivudine. An HBV-DNA breakthrough occurred 7 months after the start of therapy, and the drug was stopped after 9 months. The molecular state of HBV-DNA was analyzed, and a mutation in the YMDD (tyrosine, methionine, aspartate, aspartate) locus of HBV-DNA polymerase was identified. Nine months after the suspension of lamivudine the patient experienced a new hepatic attack accompanied by high HBV-DNA levels. Lamivudine was given again. Serum HBV-DNA levels normalized after 45 days of re-treatment, but lamivudine-resistant mutants were again the prevalent viral population after 3 months.


CONCLUSIONS
The case described suggests that retherapy with lamivudine after a first emergence of YMDD mutants is temporarily effective in recontrolling HBV synthesis but ultimately induces the accelerated reemergence of a prevalently mutant population of HBV. This emphasizes the need for combined antiviral therapy.
Marzano
A
A
Department of Gastroenterology, Molinette Hospital, Torino, Italy.
Debernardi-Venon
W
W
Condreay
L
L
Rizzetto
M
M
D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000378:metabolism*; D006509:Hepatitis B / Q000188:drug therapy* / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy*; D012008:Recurrence; D019233:Retreatment
D000998:Antiviral Agents; D004279:DNA, Viral; D019259:Lamivudine