Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants

Robert Perrillo, Eugene R Schiff, Eric Yoshida, Ann Statler, Kenneth Hirsch, Teresa Wright, Klaus Gutfreund, Patrick Lamy, Alison Murray

Research output: Contribution to journalArticle

452 Citations (Scopus)

Abstract

Lamivudine has been shown to be an effective therapy for chronic hepatitis B, but resistance to this nucleoside agent is common after prolonged use. Five patients with chronic hepatitis B virus (HBV) infection developed resistance to lamivudine after 9 to 19 months of treatment. In 4 patients this occurred after liver transplantation and the remaining individual had stable cirrhosis. In each case, resistance was confirmed to be caused by one or more mutations in the HBV-DNA polymerase gene and was associated with active underlying liver disease. The patients were treated with adefovir dipivoxil in a dose of 5 to 30 mg daily. Two to 4 log10 reductions in HBV-DNA levels were observed in 4 cases, and the fifth patient became negative by quantitative polymerase chain reaction (PCR) after retransplantation in conjunction with hepatitis B immunoglobulin (HBIg). Virologic improvement was associated with stable or declining serum alanine transaminase levels in 4 patients. HBV-DNA suppression has been sustained during a mean treatment period of 13 months (range 11 to 15 months), including 1 patient in whom lamivudine has been discontinued. Mild changes in renal function were observed during treatment in most cases but did not require early discontinuation of the drug. This study provides evidence that adefovir dipivoxil can be an effective treatment for lamivudine-resistant HBV mutants as well as wild-type HBV.

Original languageEnglish
Pages (from-to)129-134
Number of pages6
JournalHepatology
Volume32
Issue number1
StatePublished - Jul 1 2000

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Lamivudine
Hepatitis B
Hepatitis B virus
Chronic Hepatitis B
Therapeutics
DNA
Virus Diseases
DNA-Directed DNA Polymerase
Alanine Transaminase
Nucleosides
Liver Transplantation
adefovir dipivoxil
Immunoglobulins
Liver Diseases
Fibrosis
Kidney
Polymerase Chain Reaction
Mutation
Serum
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Hepatology

Cite this

Perrillo, R., Schiff, E. R., Yoshida, E., Statler, A., Hirsch, K., Wright, T., ... Murray, A. (2000). Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants. Hepatology, 32(1), 129-134.

Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants. / Perrillo, Robert; Schiff, Eugene R; Yoshida, Eric; Statler, Ann; Hirsch, Kenneth; Wright, Teresa; Gutfreund, Klaus; Lamy, Patrick; Murray, Alison.

In: Hepatology, Vol. 32, No. 1, 01.07.2000, p. 129-134.

Research output: Contribution to journalArticle

Perrillo, R, Schiff, ER, Yoshida, E, Statler, A, Hirsch, K, Wright, T, Gutfreund, K, Lamy, P & Murray, A 2000, 'Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants', Hepatology, vol. 32, no. 1, pp. 129-134.
Perrillo R, Schiff ER, Yoshida E, Statler A, Hirsch K, Wright T et al. Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants. Hepatology. 2000 Jul 1;32(1):129-134.
Perrillo, Robert ; Schiff, Eugene R ; Yoshida, Eric ; Statler, Ann ; Hirsch, Kenneth ; Wright, Teresa ; Gutfreund, Klaus ; Lamy, Patrick ; Murray, Alison. / Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants. In: Hepatology. 2000 ; Vol. 32, No. 1. pp. 129-134.
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