Journal
HEPATOLOGY INTERNATIONAL
Volume 6, Issue 2, Pages 482-490Publisher
SPRINGER
DOI: 10.1007/s12072-011-9306-7
Keywords
HCV; Protease inhibitor; Naturally occurring viral resistance mutations
Categories
Funding
- Ministry of Education, Science, Sports, and Culture [20390206]
- Ministry of Health, Labor, and Welfare of Japan [H19-kanen-002]
- Grants-in-Aid for Scientific Research [21590837, 23390195, 21390227, 20390206, 21659186, 24590964] Funding Source: KAKEN
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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.
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