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Method to detect substitutions in the interferon‐sensitivity—Determining region of hepatitis C virus 1b for prediction of response to interferon therapy
Author(s) -
Nishiguchi Shuhei,
Ueda Tadashi,
Itoh Teiji,
Enomoto Masaru,
Tanaka Motoharu,
Tatsumi Nobuyuki,
Fukuda Katsuhiko,
Tamori Akihiro,
Habu Daiki,
Takeda Tadashi,
Otani Shuzo,
Shiomi Susumu
Publication year - 2001
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.2001.20795
Subject(s) - interferon , virology , hepatitis c virus , medicine , sensitivity (control systems) , hepatitis c , virus , immunology , electronic engineering , engineering
Abstract Substitutions deduced by direct sequencing in the interferon‐sensitivity—determining region (ISDR) of hepatitis C virus (HCV) are related to patients' responses to interferon (IFN), but sequencing is time consuming and results are only for the dominant virus. We developed a rapid method to detect such changes. With serum from 50 patients with chronic hepatitis C (genotype 1b) given IFN‐α, a way to detect changes in ISDR by hybridization with oligonucleotide probes that had a prototype nucleotide sequence of HCV‐J was established. Hybridization intensity was expressed as optical density (OD NS5A ). The method was checked with serum from 100 more patients. In the study of 50 patients, all 21 with the prototype sequences had a high OD NS5A (≥0.4), and all 8 patients with a mutant‐type sequence had low values (≤0.2). Twelve (95% confidence interval, 36‐81%) of 20 patients with OD NS5A of <0.4 and 2 (1%‐22%) of 30 patients with OD NS5A ≥0.4 had complete responses (CR). All nine (66%‐100%) patients with OD NS5A <0.4 and little HCV RNA (<100 kIU/mL) had CR, but none (0%‐14%) of the 24 patients with high values from both predictors had CR. In the study of 100 patients, OD NS5A and the HCV RNA level were independent predictors of the effects of IFN. By multivariate analysis, the odds ratio for a CR in patients with OD NS5A of ≥0.4 was 0.015 (0.001‐0.190) compared with the other patients ( P = .001). In conclusion, our method should be useful in identification of prototype strains, which generally resist IFN therapy.