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.