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  • Sequences in the NS5A protein of hepatitis C virus and the serum alanine aminotransferase response to interferon therapy in Japanese patients

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Liver disease
Sequences in the NS5A protein of hepatitis C virus and the serum alanine aminotransferase response to interferon therapy in Japanese patients
  1. K Nagayamaa,
  2. N Enomotoa,
  3. N Izumib,
  4. M Kurosakia,
  5. Y Miyasakaa,
  6. H Watanabea,
  7. J Itakuraa,
  8. C-H Chena,
  9. J Tazawac,
  10. Y Hoshinod,
  11. T Ikedad,
  12. F Marumoa,
  13. C Satoe
  1. aSecond Department of Internal Medicine, Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan, 113-8519, bDepartment of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1 Kyonan-cho, Musashino city, Tokyo, Japan, 180-8610, cDepartment of Internal Medicine, Tsuchiura Kyodo General Hospital, 14-7 Manabe-shinmachi, Tsuchiura city, Ibaraki, Japan, 300-0053, dSecond Department of Internal Medicine, Yokosuka Kyosai General Hospital, 22-7 Yonegahama-dori, Yokosuka city, Kanagawa, Japan, 238-0011, eDepartment of Health Science, Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan, 113-8519
  1. Dr N Enomoto.nenomoto.med2{at}med.tmd.ac.jp

Abstract

BACKGROUND AND AIMS Chronic hepatitis C is a slowly progressive disease and eventually causes hepatocellular carcinoma in many patients. Although interferon (IFN) therapy has been used for viral eradication, its success rate is only about 30%. In patients in whom it has failed (non-responders), there are several patterns of serum alanine aminotransferase (ALT) values, and detection of serum HCV-RNA during and after IFN therapy and improved long term prognosis were reported in patients whose serum ALT values were normalised by IFN therapy even if HCV viraemia persisted. The present study sought to clarify the virological characteristics contributing to these differences.

METHODS Complete or partial length dominant sequences of hepatitis C virus genotype 1b (HCV-1b) were determined by direct sequencing. Firstly, the complete sequences of HCV-1b genomes were determined in six non-responders; three showed normalisation of serum ALT values during IFN-α therapy and the other three did not. Subsequently, the amino acid residues that were different in the two groups were further analysed retrospectively in another 82 patients.

RESULTS Comparison of the sequences suggested an association between amino acids 2154–2172 of HCV-1b and serum ALT normalisation. A retrospective analysis of 82 patients revealed that the number of amino acid substitutions in this region was the only statistically significant variable associated with ALT normalisation (odds ratio 31.0; 95% confidence interval 5.0–286) in multivariate analyses.

CONCLUSIONS A HCV genomic region that correlates with the ALT response to IFN therapy appears to be present in virologically IFN ineffective patients.

  • hepatitis C virus
  • alanine aminotransferase
  • biochemical responder
  • transient responder
  • NS5A protein

  • Abbreviations used in this paper

    IFN
    interferon
    ALT
    alanine aminotransferase
    HCV
    hepatitis C virus
    HCV-1b
    HCV genotype 1b
    HCC
    hepatocellular carcinoma
    CR
    complete responder
    NR
    non-responder
    BR
    biochemical responder
    TR
    transient responder
    ISDR
    interferon sensitivity determining region
    NCR
    non-coding region
    PCR
    polymerase chain reaction
    ARE
    ALT response related element
    HCV-2a
    HCV genotype 2a
    HCV-2b
    HCV genotype 2b
    CTL
    cytotoxic T lymphocytes

    • https://doi.org/10.1136/gut.48.6.830

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    • Abbreviations used in this paper

      IFN
      interferon
      ALT
      alanine aminotransferase
      HCV
      hepatitis C virus
      HCV-1b
      HCV genotype 1b
      HCC
      hepatocellular carcinoma
      CR
      complete responder
      NR
      non-responder
      BR
      biochemical responder
      TR
      transient responder
      ISDR
      interferon sensitivity determining region
      NCR
      non-coding region
      PCR
      polymerase chain reaction
      ARE
      ALT response related element
      HCV-2a
      HCV genotype 2a
      HCV-2b
      HCV genotype 2b
      CTL
      cytotoxic T lymphocytes
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