Prior studies have suggested that natural killer (NK) cell function might be impaired in chronic hepatitis C virus (HCV) infection. Circulating NK cell frequency and cytolytic activity were examined freshly ex vivo in HCV-infected and uninfected subjects. Surprisingly, the intrinsic cytolytic activity of peripheral blood NK-enriched cells was similar between HCV-infected and uninfected groups (P ‫؍‬ .91). Although the percentage of circulating CD3 ؊ CD16/56 ؉ NK cells was 30% lower in HCV-infected compared with uninfected subjects (P ‫؍‬ .02) paralleled by a decrease of CD56 dim cytolytic NK cells (P ‫؍‬ .02), overall K562 cytolysis by unfractionated peripheral blood mononuclear cells was not affected (P ‫؍‬ .29). Analysis of the relationships between NK cytolytic activity and other clinical information revealed an inverse association with liver fibrosis stage (P ‫؍‬ .035). In conclusion, NK cell cytolytic function does not appear to be impaired in chronic hepatitis C, but higher levels of NK cell cytolysis are associated with less liver fibrosis. ( H epatitis C virus (HCV) is able to establish a chronic persistent infection in the vast majority of individuals exposed, 1 making it likely that the virus uses multiple strategies to elude the immune response it elicits. Several groups have demonstrated that hepatitis C-specific adaptive immunity is attenuated in chronic disease. 2-5 However, relatively little is known about the role of the innate immune response in hepatitis C, despite the fact that innate immunity has the ability to significantly influence the subsequent adaptive immune response. [6][7][8] A number of investigators have studied natural killer (NK) cell function on exposure to HCV components in vitro, with intriguing results. Tseng et al. 9 and Crotta et al. 10 simultaneously reported that NK cell function could be diminished in vitro by interactions with HCV envelope protein E2, anti-E2 antibody (via CD81), and anti-CD16. Whereas one implication from these studies is that diminished NK cell function early in the course of acute infection may explain HCV persistence, the effects described by these investigators could also pertain to chronic infection. However, studies of ex vivo NK cell function in patients with chronic hepatitis C have yielded mixed results. Corado and colleagues first reported that NK cell cytotoxicity was compromised in chronic hepatitis C compared with healthy negative controls, 11 using a well-established human NK cell target cell line, K562. 12 Similar data were published by Par and colleagues, 13 but Duesberg et al. recently demonstrated that cytotoxicity and antibody-dependent cell-mediated cytotoxicity against HT29 cells were not adversely affected in chronic hepatitis C. 14 Moreover, Kawarabayashi et al. found no difference in K562 cytolysis between liver mononuclear cells containing a mean of 31% CD56 ϩ NK cells between 12 HCV-negative and 12 HCV-infected subjects without cirrhosis. 15 Thus, the existence of an in vivo NK cell defect in chronic HCV infection has not been...

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