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

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

This 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.

Methods

A 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.

Results

Of 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.

Conclusion

IRRDR ≥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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Acknowledgments

This work was supported in part by Grants-in-Aid for Research on Hepatitis from the Ministry of Health, Labor and Welfare, Japan, and a SATREPS Grant from JST and JICA. The study was also carried out as part of the J-GRID Program, Ministry of Education, Culture, Sports, Science and Technology, Japan, and the G-COE Program at Kobe University Graduate School of Medicine. We are indebted to Ms. Yoshiko Kawamura of Kobe Asahi Hospital for assistance in the preparation of the manuscript.

Conflict of interest

None of the authors has any conflict of interest.

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Authors and Affiliations

  1. Department of Gastroenterology, Kobe Asahi Hospital, 3-5-25 Bououji-cho, Nagata-ku, Kobe, 653-0801, Japan

    Soo Ryang Kim, Susumu Imoto & Ke Ih Kim

  2. Division of Microbiology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan

    Ahmed El-Shamy, Yoshi-hiro Ide, Lin Deng, Ikuo Shoji & Hak Hotta

  3. Department of Virology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt

    Ahmed El-Shamy

  4. Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Yasuhito Tanaka

  5. Educational Center for Clinical Pharmacy, Kobe Pharmaceutical University, Kobe, Japan

    Yutaka Hasegawa

  6. Medical Biochemistry, Kobe Pharmaceutical University, Kobe, Japan

    Mitsuhiro Ota

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  1. Soo Ryang Kim
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  2. Ahmed El-Shamy
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Correspondence to Soo Ryang Kim.

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Kim, S.R., El-Shamy, A., Imoto, S. et al. Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotype 1b and high viral load. J Gastroenterol 47, 1143–1151 (2012). https://doi.org/10.1007/s00535-012-0578-z

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  • DOI: https://doi.org/10.1007/s00535-012-0578-z

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