Sustained response to interferon-α plus ribavirin therapy for chronic hepatitis C is closely associated with increased dynamism of intrahepatic natural killer and natural killer T cells

  1. Satoshi Yamagiwa1,*,
  2. Yasunobu Matsuda1,
  3. Takafumi Ichida3,
  4. Yutaka Honda1,
  5. Masaaki Takamura1,
  6. Satoshi Sugahara1,
  7. Toru Ishikawa1,
  8. Shogo Ohkoshi1,
  9. Yoshinobu Sato2,
  10. Yutaka Aoyagi1

Article first published online: 5 MAR 2008

DOI: 10.1111/j.1872-034X.2008.00317.x

Issue

Hepatology Research

Hepatology Research

Volume 38, Issue 7, pages 664–672, July 2008

Additional Information

How to Cite

Yamagiwa, S., Matsuda, Y., Ichida, T., Honda, Y., Takamura, M., Sugahara, S., Ishikawa, T., Ohkoshi, S., Sato, Y. and Aoyagi, Y. (2008), Sustained response to interferon-α plus ribavirin therapy for chronic hepatitis C is closely associated with increased dynamism of intrahepatic natural killer and natural killer T cells. Hepatology Research, 38: 664–672. doi: 10.1111/j.1872-034X.2008.00317.x

Author Information

  1. 1

    Division of Gastroenterology and Hepatology,

  2. 2

    Division of Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, and

  3. 3

    Division of Gastroenterology and Hepatology, Juntendo University School of Medicine Shizuoka Hospital, Izunokuni, Japan

*Dr Satoshi Yamagiwa, Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 757 Asahimachi-dori 1, Chuo-ku, Niigata 951-8510, Japan. Email: syamagi@med.niigata-u.ac.jp

Publication History

  1. Issue published online: 5 MAR 2008
  2. Article first published online: 5 MAR 2008
  3. Received 3 July 2007; revision 27 November 2007; accepted 28 November 2007.

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Keywords:

  • chronic hepatitis C;
  • interferon;
  • intrahepatic lymphocytes;
  • natural killer cells;
  • natural killer T cells

Aim:  Previous studies have revealed that functional impairment of innate immune cells, including natural killer (NK) and natural killer T (NKT) cells, might be associated with the persistence of hepatitis C virus (HCV) infection. However, the involvement of innate immune cells, which predominate in the liver, in therapeutic HCV clearance is still unclear.

Methods:  To clarify the role of intrahepatic innate immune cells in the clinical outcome of patients with chronic hepatitis C (CHC) treated with interferon-α plus ribavirin (IFN/RBV), we prospectively investigated the status of NK and NKT cells in paired liver biopsy and peripheral blood (PB) samples obtained from 21 CHC patients before and immediately after IFN/RBV treatment by flow cytometry. Normal liver and PB samples were obtained from 10 healthy donors for living donor liver transplantation.

Results:  Before treatment, intrahepatic NK and NKT cells constituted a significantly lower proportion in CHC patients than in healthy individuals (P < 0.05). After IFN/RBV treatment, the proportions and absolute numbers of CD3-CD161+ NK and CD3+CD56+ NKT cells in the liver, but not in PB, were significantly increased in sustained responders (SR) as compared with poor responders (P < 0.05). The proportion of CD3+CD161+ NKT cells was also increased in the liver of SR after the treatment. Moreover, there was a striking increase of activated CD152+ cells among CD3+CD56+ NKT cells in the liver of SR (P = 0.041).

Conclusion:  These findings demonstrate that sustained response to IFN/RBV treatment for patients with CHC is closely associated with increased dynamism of NK and NKT cells in the liver.

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