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Value of interleukin-28B genetic polymorphism on retreatment outcomes of chronic hepatitis C genotype 1 relapsers by peginterferon alfa plus ribavirin

Authors

  • Ming-Yao Chen,

    1. Department of Internal Medicine, Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan
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  • Chen-Hua Liu,

    1. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • Ting-Chih Chen,

    1. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • Tung-Hung Su,

    1. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • Pei-Jer Chen,

    1. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
    2. Department of Internal Medicine, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
    3. Hepatitis Research Center, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
    4. Department of Medical Research, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • Ding-Shinn Chen,

    1. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
    2. Department of Internal Medicine, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
    3. Hepatitis Research Center, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • Jia-Horng Kao,

    Corresponding author
    1. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
    2. Department of Internal Medicine, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
    3. Hepatitis Research Center, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
    4. Department of Medical Research, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
    • Correspondence

      Dr Chun-Jen Liu, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te Street, Taipei 10002, Taiwan. Email: cjliu@ntu.edu.tw

      Or

      Professor Jia-Horng Kao, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te Street, Taipei 10002, Taiwan. Email: kaojh@ntu.edu.tw

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  • Chun-Jen Liu

    Corresponding author
    1. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
    2. Department of Internal Medicine, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
    3. Hepatitis Research Center, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
    • Correspondence

      Dr Chun-Jen Liu, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te Street, Taipei 10002, Taiwan. Email: cjliu@ntu.edu.tw

      Or

      Professor Jia-Horng Kao, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te Street, Taipei 10002, Taiwan. Email: kaojh@ntu.edu.tw

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  • There are no potential conflicts of interest to declare.
  • None of the materials and results has been presented or published previously.
  • No writing assistance was provided.
  • Financial disclosure: The work was supported by grants from the National Taiwan University; the National Science Council and Department of Health, Executive Yuan, Taiwan; and National Taiwan University Hospital, Taiwan.

Abstract

Background and Aim

Chronic hepatitis C (CHC) infection is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Pegylated interferon (PEG-IFN) plus ribavirin (RBV) combination therapy remains the standard of care for CHC genotype 1 in many Asian countries, and single nucleotide polymorphism or genotype of the interleukin-28B (IL28B) gene is associated with the development of sustained virologic response (SVR). The predictive value of IL28B genotype for retreatment outcomes of patients with CHC was only partly clarified and deserves further investigation.

Methods

A total of 75 CHC genotype 1 Taiwanese patients who relapsed after 24-week PEG-IFN/RBV combination therapy and received retreatment with a 48-week PEG-IFN/RBV therapy were consecutively enrolled since November 2009. The associations among IL28B rs8099917 genotype, virologic kinetics, and treatment outcomes were evaluated.

Results

Rapid virologic response (RVR) at week 4, end-of-treatment virologic response (EOT-VR) and SVR was 37%, 73%, and 52%, respectively. Relapse rate was 29%. None of patients had rs8099917 GG genotype. Patients with TT genotype (n = 54, 72%) had higher rates of RVR (50% vs 5%, P = 0.0002), end-of-treatment virologic response (85% vs 43%, P = 0.0001), and SVR (67% vs 14%, P = 0.0001) than those with GT genotype (n = 21, 28%). Combination of IL28B TT genotype and achieving RVR had 85% positive and 90% negative predictive values of SVR.

Conclusions

About half of the Taiwanese CHC relapsers to a previous 24-week combination therapy achieve SVR after retreatment for 48 weeks. IL28B genotype influences on-treatment viral kinetics and SVR rate in these retreated patients. Baseline IL28B genotype and RVR can serve as early predictors for treatment success.

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