Elsevier

Transplantation Proceedings

Volume 36, Issue 8, October 2004, Pages 2313-2314
Transplantation Proceedings

Adefovir dipivoxil as the rescue therapy for lamivudine-resistant hepatitis B post liver transplant

https://doi.org/10.1016/j.transproceed.2004.06.047Get rights and content

Abstract

Introduction

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 μmol/L (P = 0.72).

Conclusion

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.

Section snippets

Patients and methods

Between 1990 to 2002, 22 adult patients underwent 23 liver transplants for HBV-related liver disease. Sixteen (73%) were still alive at their last follow-up. None of the 6 who died posttransplant died of HBV-related complications. All patients with HBV-related liver disease who are on the waiting list were given oral lamivudine (100 to 300 mg per day) for at least 4 weeks prior to and indefinitely after liver transplant. HBV DNA was measured every 3 months pretransplant and posttransplant using

Results

Sixteen adult patients transplanted for HBV-related complications were alive at the last follow-up (median 46 [range 9 to 74] months posttransplant). Median (range) recipient age was 49 years (40 to 60). All were men. Indications for transplantation were decompensated cirrhosis in nine, hepatocellular carcinoma in six, and severe acute exacerbation in one. All but one patient had undetectable HBV DNA at the time of transplant. That patient had been on lamivudine (100 mg) for 8 months prior to

Discussion

This study showed that emergence of lamivudine-resistant HBV was common among the recipients on lamivudine monotherapy. However, clinical deterioration only occurred in four of the six patients with HBV recurrence, suggesting that lamivudine-resistant HBV may not be universally aggressive. In fact, one patient with HBV recurrence had persistently undetectable HBV DNA by Digene, with normal transaminase values and liver biopsy at 46 months after HBV recurrence.

Our study also showed that

Acknowledgement

The authors express sincere appreciation to Ms Jasminder Kaur for her clerical assistance.

References (4)

  • C.T. Wai et al.

    Outcome of lamivudine resistant hepatitis B virus infection in liver transplant recipients in Singapore

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    (2000)
  • D. Multimer et al.

    Outcome of lamivudine resistant hepatitis B virus infection in the liver transplant recipient

    Gut

    (2000)
There are more references available in the full text version of this article.

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