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Hepatology International
Published in: Hepatology International 1/2010

01-03-2010 | Original Article

Efficacy and resistance of entecavir following 3 years of treatment of Japanese patients with lamivudine-refractory chronic hepatitis B

Authors: Yoshiyasu Karino, Joji Toyota, Hiromitsu Kumada, Yoshiaki Katano, Namiki Izumi, Haruhiko Kobashi, Michio Sata, Mitsuhiko Moriyama, Fumio Imazeki, Masayoshi Kage, Hiroki Ishikawa, Nobuyuki Masaki, Taku Seriu, Masao Omata

Published in: Hepatology International | Issue 1/2010

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Abstract

Purpose

Lamivudine treatment of chronic hepatitis B (CHB) is associated with frequent resistance and loss of clinical benefit. We present outcomes of lamivudine-refractory Japanese patients treated with entecavir for 3 years.

Methods

Eighty-two patients refractory to lamivudine therapy received entecavir 0.5 or 1 mg daily for 52 weeks in phase II study ETV-052, directly entered rollover study ETV-060, and received entecavir 1 mg daily. Responses were evaluated among patients with available samples.

Results

After 96 weeks in ETV-060 (148 weeks total entecavir treatment time), 55% (36/65) of patients had hepatitis B virus (HBV) DNA of >400 copies/mL, 85% (52/61) had alanine aminotransferase (ALT) of ≥1 × upper limit of normal (ULN), and 14.6% (7/48) achieved HBe seroconversion. A subset of 42 patients received entecavir 1 mg from phase II baseline through 148 weeks: 54% (19/35) had HBV DNA of >400 copies/mL, 84% (27/32) had ALT of ≥1 × ULN, and 15% (4/27) achieved HBe seroconversion. Sixteen patients in the 1-mg subset had baseline and week 148 evaluable biopsy pairs: 81% (13/16) showed histologic improvement and 38% (6/16) showed improvement in fibrosis. Genotypic resistance to entecavir emerged in 31 patients for a 3-year cumulative resistance probability of 35.9%. Entecavir was generally well tolerated during ETV-060, with no on-treatment ALT flares.

Conclusions

Long-term entecavir treatment of lamivudine-refractory CHB resulted in virologic suppression, ALT normalization, and improvements in liver histology. Resistance was consistent with that observed in worldwide studies.
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Metadata
Title
Efficacy and resistance of entecavir following 3 years of treatment of Japanese patients with lamivudine-refractory chronic hepatitis B
Authors
Yoshiyasu Karino
Joji Toyota
Hiromitsu Kumada
Yoshiaki Katano
Namiki Izumi
Haruhiko Kobashi
Michio Sata
Mitsuhiko Moriyama
Fumio Imazeki
Masayoshi Kage
Hiroki Ishikawa
Nobuyuki Masaki
Taku Seriu
Masao Omata
Publication date
01-03-2010
Publisher
Springer-Verlag
Published in
Hepatology International / Issue 1/2010
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-009-9162-x

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