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Successful treatment of an entecavir‐resistant hepatitis B virus variant
Author(s) -
Yatsuji Hiromi,
Hiraga Nobuhiko,
Mori Nami,
Hatakeyama Tsuyoshi,
Tsuge Masataka,
Imamura Michio,
Takahashi Shoichi,
Fujimoto Yoshifumi,
Ochi Hidenori,
Abe Hiromi,
Maekawa Toshiro,
Suzuki Fumitaka,
Kumada Hiromitsu,
Chayama Kazuaki
Publication year - 2007
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.20981
Subject(s) - entecavir , adefovir , virology , lamivudine , hepatitis b virus , mutant , reverse transcriptase , orthohepadnavirus , virus , biology , hepadnaviridae , rna , biochemistry , gene
Emergence of a lamivudine (LAM)‐resistant hepatitis B virus (HBV) with amino acid substitutions in the YMDD motif is a well‐documented problem during long‐term LAM therapy. Entecavir (ETV) is a new drug approved for treatment of HBV infection with or without LAM‐resistant mutants. This report describes an ETV‐resistant strain of HBV, which emerged after prolonged ETV therapy in a patient who did not respond to LAM therapy. Direct sequence analysis of the ETV‐resistant strain showed appearance of amino acid substitution rtS202G in the reverse transcriptase (RT) domain, together with rtL180M + M204V substitution that had developed at the emergence of LAM‐resistant mutant. In vitro analysis demonstrated that the rtL180M + M204V + S202G mutant strain displayed a 200‐fold and a 5‐fold reduction in susceptibility to ETV compared with the wild‐ type and the rtL180M + M204V mutant strain, respectively. Adefovir was effective against the ETV‐resistant strain both in vitro and during the clinical course. In conclusion, this study showed that virological and biochemical breakthrough due to ETV could occur in patients infected with LAM‐resistant HBV and confirmed that the addition of rtS202G substitution to the rtL180M + M204V mutant strain is responsible for ETV resistance and we could treat the resistant mutant successfully. J. Med. Virol. 79:1811–1817, 2007. © 2007 Wiley‐Liss, Inc.