Adefovir dipivoxil as the rescue therapy for lamivudine-resistant hepatitis B post liver transplant.
BACKGROUND
Complications of hepatitis B virus (HBV) infection are among the most common indications for liver transplant in many parts of Asia. However, none of the current posttransplant hepatitis B prophylaxis strategies, namely, lamivudine, hepatitis B immunoglobulin monotherapy, or combination therapy, is ideal. Our aim was to evaluate the use of adefovir dipivoxil (ADV) as a rescue therapy for posttransplant HBV patients who developed lamivudine resistance.


METHODS
Twenty-two consecutive patients with HBV-related liver disease, who underwent first liver transplants from 1995 to 2002, received HBV prophylaxis with indefinite lamivudine with substitution of ADV for patients who developed drug resistance and clinical deterioration, defined as persistent elevation of transaminases or histologic deterioration.


RESULTS
Sixteen patients (73%) were alive at their last follow-up and six (38%) had developed hepatitis B recurrence at a median of 46 (range 9 to 74) months posttransplant. Two with persistently normal transaminases and normal liver histology at 3 and 42 months postrecurrence have been continued on lamivudine. Four showed clinical deterioration and received ADV for a median of 24 months; all displayed normalization of transaminases and a 2 to 5 log drop in HBV DNA titers. Three had paired biopsies before and after substitution of ADV with two showing improvement and one stable appearance. The median serum creatinine value increased slightly from 126 to 138 micromol/L (P = 0.72).


CONCLUSIONS
ADV is an effective rescue therapy for patients with lamivudine-resistant hepatitis B post-liver transplant. Further studies are needed to ascertain the optimal posttransplant hepatitis B prophylaxis.
Wai
C-T
CT
Singapore Liver Transplant Program, National University Hospital, Singapore. waict@nuh.com.sg
Prabhakaran
K
K
Wee
A
A
Lee
Y-M
YM
Dan
Y-Y
YY
Sutedja
D S
DS
Mak
K
K
Isaac
J
J
Lee
K-H
KH
Lee
H-L
HL
Da Costa
M
M
Lim
S-G
SG
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D004351:Drug Resistance; D005500:Follow-Up Studies; D006509:Hepatitis B / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects*; D016031:Liver Transplantation / Q000009:adverse effects; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000821:virology; D012008:Recurrence; D012189:Retrospective Studies
D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; D000225:Adenine; C106812:adefovir dipivoxil