Introduction Chronic hepatitis C virus (HCV) infection is a major cause of liver failure, cirrhosis and hepatocellular carcinoma. Current treatments are evolving but still largely rely on IFNα in combination with ribavirin +/- protease inhibitors. IFNa can activate Natural killer (NK) cells: large granular lymphocytes that can target virally-infected cells. NK cells may play a role in the immune response to chronic HCV. We examined whether the kinetics of NK cell expansion and activation affected long-term treatment success.
Methods Repeated matched blood and intrahepatic (IH) NK cells were obtained from 9 patients before treatment and on days 1, 3, 7, 14, 28 and 86 of treatment. IH samples were obtained by fine needle aspirations. NK cell phenotype (CD16, NKp30, NKp46 & NKG2D) and functional markers (CD107a, IFNg & granzyme B) were assessed by flow cytometry. Rate of viral clearance (k) was calculated from serial serum viral loads during treatment.
Results Multiple IH samples were obtained from 9 subjects. 5 of the 9 patients achieved viral clearance i.e. SVR; 4 failed treatment. The proportion of IH lymphocytes that were NK cells increased from mean 10% (+/-0.97% SEM) at baseline to 16.1% (+/- 2.43% SEM) after 24 hours (p = 0.021) and 17.9% (+/-4.75% SEM) after 72 hours (p = 0.023). The proportions returned to baseline levels from day 7 onwards. The proportion of IH NK cells was greater in patients who achieved SVR (18.6%) than those who failed treatment (11.9%). The rate of viral clearance correlates with IH NK cells at day 1 (p = 0.036). IH NK cells at 24 hours demonstrated an increase in activation i.e. increase CD107a externalisation, decreased granzyme B and CD16 expression.
Conclusion IH NK cells are cytotoxically active during the early phase of treatment when reduction in viral load is most pronounced. The rate of expansion of these activated NK cells in the first 24 hours indicates treatment success or failure. These findings suggest that strategies to improve early NK cell migration to the liver during treatment may lead to better treatment outcomes.
Disclosure of Interest None Declared
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