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Hepatology International

, Volume 6, Issue 2, pp 482–490 | Cite as

Characterization of naturally occurring protease inhibitor-resistance mutations in genotype 1b hepatitis C virus patients

  • Hiroko Shindo
  • Shinya MaekawaEmail author
  • Kazuki Komase
  • Ryota Sueki
  • Mika Miura
  • Makoto Kadokura
  • Kuniaki Shindo
  • Fumitake Amemiya
  • Takatoshi Kitamura
  • Yasuhiro Nakayama
  • Taisuke Inoue
  • Minoru Sakamoto
  • Shun-ichi Okada
  • Yasuhiro Asahina
  • Namiki Izumi
  • Masao Honda
  • Shuichi Kaneko
  • Nobuyuki Enomoto
Original Article

Abstract

Background and aims

Protease inhibitor (PI)-resistant hepatitis C virus (HCV) variants may be present in substantial numbers in PI-untreated patients according to recent reports. However, influence of these viruses in the clinical course of chronic hepatitis C has not been well characterized.

Methods

The dominant HCV nonstructural 3 (NS3) amino acid sequences were determined in 261 HCV genotype 1b-infected Japanese patients before pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy, and investigated the patients’ clinical characteristics as well as treatment responses including sustained virological response (SVR) rate. HCV-NS3 sequences were also determined in 39 non-SVR patients after completion of the therapy.

Results

Four single mutations (T54S, Q80K, I153V, and D168E) known to confer PI resistance were found in 35 of 261 patients (13.4%), and double mutations (I153V plus T54S/D168E) were found in 6 patients (2.3%). Responses to PEG-IFN/RBV therapy did not differ between patients with and without PI-resistance mutations (mutation group, SVR 48%; wild-type group, SVR 40%; P = 0.38). On the other hand, two mutations appeared in two non-SVR patients after PEG-IFN/RBV therapy (I153V and E168D, 5.1%).

Conclusions

PI-resistance-associated NS3 mutations exist in a substantial proportion of untreated HCV-1b-infected patients. The impact of these mutations in the treatment of PIs is unclear, but clinicians should pay attention to avoid further development of PI resistance.

Keywords

HCV Protease inhibitor Naturally occurring viral resistance mutations 

Notes

Acknowledgements

This work was supported in part by a grant-in-aid scientific research fund from the Ministry of Education, Science, Sports, and Culture [grant number 20390206] and in part by a grant-in-aid from the Ministry of Health, Labor, and Welfare of Japan [grant number H19-kanen-002].

Supplementary material

12072_2011_9306_MOESM1_ESM.doc (34 kb)
Supplementary material 1 (DOC 34 kb)

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Copyright information

© Asian Pacific Association for the Study of the Liver 2011

Authors and Affiliations

  • Hiroko Shindo
    • 1
  • Shinya Maekawa
    • 1
    Email author
  • Kazuki Komase
    • 1
  • Ryota Sueki
    • 1
  • Mika Miura
    • 1
  • Makoto Kadokura
    • 1
  • Kuniaki Shindo
    • 1
  • Fumitake Amemiya
    • 1
  • Takatoshi Kitamura
    • 1
  • Yasuhiro Nakayama
    • 1
  • Taisuke Inoue
    • 1
  • Minoru Sakamoto
    • 1
  • Shun-ichi Okada
    • 1
  • Yasuhiro Asahina
    • 2
  • Namiki Izumi
    • 2
  • Masao Honda
    • 3
  • Shuichi Kaneko
    • 3
  • Nobuyuki Enomoto
    • 1
  1. 1.First Department of Internal MedicineUniversity of YamanashiChuoJapan
  2. 2.Division of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
  3. 3.Department of GastroenterologyKanazawa University Graduate School of MedicineKanazawaJapan

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