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
Article first published online: 5 MAR 2008
© 2008 The Japan Society of Hepatology
Volume 38, Issue 7, pages 664–672, July 2008
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
- Issue published online: 5 MAR 2008
- Article first published online: 5 MAR 2008
- Received 3 July 2007; revision 27 November 2007; accepted 28 November 2007.
- chronic hepatitis C;
- 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.