impaired activity of NK (natural killer) cells has been proposed as a mechanism contributing to viral persistence and chronic infection in hepatitis C (HCV) infection. We aimed to assess the impact of HCV infection on NK cells regarding frequency, subset distribution, and cytotoxic and cytokine secretion functions, as well as IFN-alpha and ribavirin therapeutic effects on NK cells. Significant reduction of total NK frequency and the CD56(dim)16(+) subset was observed in chronic HCV patients. IFN-gamma expression upon stimulation with K562 was severely suppressed but cytotoxicity measured by CD107a expression was maintained. These adverse effects were reversed after treatment with pegylated IFN-alpha and ribavirin; however, these skewed functions were not recovered in treatment-resistant patients. Thus, HCV chronic infection severely affects NK functions, except for cytotoxicity. Altered NK cell frequency and cytokine secretion by HCV infection may contribute to impaired cellular immune response and virus persistence. (C) 2010 Elsevier Inc. All rights reserved.