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Adefovir dipivoxil for the treatment of lamivudine‐resistant hepatitis B mutants
Author(s) -
Perrillo Robert,
Schiff Eugene,
Yoshida Eric,
Statler Ann,
Hirsch Kenneth,
Wright Teresa,
Gutfreund Klaus,
Lamy Patrick,
Murray Alison
Publication year - 2000
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2000.8626
Subject(s) - adefovir , lamivudine , hepatitis b virus , gastroenterology , medicine , hepatitis b , virology , discontinuation , nucleoside analogue , liver function , cirrhosis , hepatitis b immune globulin , liver transplantation , virus , transplantation , biology , nucleoside , biochemistry
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 log 10 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.