title: Sustained response to interferon-alpha plus ribavirin therapy for chronic hepatitis C is closely associated with increased dynamism of intrahepatic natural killer and natural killer T cells.
abstract: OBJECTIVE
  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-alpha 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamagiwa
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ichida
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Honda
authors.forename: Masaaki
authors.initials: M
authors.lastname: Takamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sugahara
authors.forename: Toru
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Shogo
authors.initials: S
authors.lastname: Ohkoshi
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Sato
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Aoyagi