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Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotype 1b and high viral load

Authors
  • Kim, Soo Ryang1
  • El-Shamy, Ahmed2, 3
  • Imoto, Susumu1
  • Kim, Ke Ih1
  • Ide, Yoshi-hiro2
  • Deng, Lin2
  • Shoji, Ikuo2
  • Tanaka, Yasuhito4
  • Hasegawa, Yutaka5
  • Ota, Mitsuhiro6
  • Hotta, Hak2
  • 1 Kobe Asahi Hospital, Department of Gastroenterology, 3-5-25 Bououji-cho, Nagata-ku, Kobe, 653-0801, Japan , Kobe (Japan)
  • 2 Kobe University Graduate School of Medicine, Division of Microbiology, Center for Infectious Diseases, Kobe, Japan , Kobe (Japan)
  • 3 Suez Canal University, Department of Virology, Faculty of Veterinary Medicine, Ismailia, Egypt , Ismailia (Egypt)
  • 4 Nagoya City University Graduate School of Medical Sciences, Department of Virology and Liver Unit, Nagoya, Japan , Nagoya (Japan)
  • 5 Kobe Pharmaceutical University, Educational Center for Clinical Pharmacy, Kobe, Japan , Kobe (Japan)
  • 6 Kobe Pharmaceutical University, Medical Biochemistry, Kobe, Japan , Kobe (Japan)
Type
Published Article
Journal
Journal of Gastroenterology
Publisher
Springer Japan
Publication Date
Mar 24, 2012
Volume
47
Issue
10
Pages
1143–1151
Identifiers
DOI: 10.1007/s00535-012-0578-z
Source
Springer Nature
Keywords
License
Yellow

Abstract

BackgroundThis study explores pretreatment predictive factors for ultimate virological responses to pegylated interferon-α (1.5 μg/kg/week) and ribavirin (600–1000 mg/day) (PEG-IFN/RBV) combination therapy for patients infected with hepatitis C virus (HCV)-1b and a high viral load.MethodsA total of 75 patients underwent PEG-IFN/RBV combination therapy for 48 weeks. HCV amino acid (aa) substitutions in non-structural protein 5a, including those in the IFN/RBV resistance-determining region (IRRDR) and the IFN sensitivity-determining region and the core regions, as well as the genetic variation (rs8099917) near the interleukin 28B (IL28B) gene (genotype TT) were analyzed.ResultsOf the 75 patients, 49 % (37/75) achieved a sustained virological response (SVR), 27 % (20/75) showed relapse, and 24 % (18/75) showed null virological response (NVR). Multivariate logistic regression analysis identified IRRDR with 6 or more mutations (IRRDR ≥6) [odds ratio (OR) 11.906, p < 0.0001] and age <60 years (OR 0.228, p = 0.015) as significant determiners of SVR and IL28B minor (OR 14.618, p = 0.0019) and platelets <15 × 104/mm3 (OR 0.113, p = 0.0096) as significant determiners of NVR. A combination of IRRDR ≥6 and age <60 years improved SVR predictability (93.3 %), and that of IRRDR ≤5 and age ≥60 years improved non-SVR predictability (84.0 %). Similarly, a combination of IL28B minor and platelets <15 × 104/mm3 improved NVR predictability (85.7 %), and that of IL28B major and platelets ≥15 × 104/mm3 improved non-NVR (response) (97.1 %) predictability.ConclusionIRRDR ≥6 and age <60 years were significantly associated with SVR. IL28B minor and platelets <15 × 104/mm3 were significantly associated with NVR. Certain combinations of these factors improved SVR and NVR predictability and could, therefore, be used to design therapeutic strategies.

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