Impaired circulating CD56^dim NK cells are associated with decompensation of HBV-related cirrhosis

NK cells play an important role in immune regulation and defense of infection, but their characteristics in patients with decompensated cirrhosis and their relationship with liver function remain unclear. We studied the functional properties of NK cells (including CD56^dim NK and CD56^bright NK cells) in patients with HBV-related decompensated liver cirrhosis (HBV-DLC) and analyzed their relationship with decompensation of liver function. Thirty patients with HBV-DLC and 25 patients with HBV-related compensated liver cirrhosis (HBV-CLC) were recruited in this study. Twenty five age- and sex-matched healthy individuals were recruited as healthy controls (HCs). The phenotypical and functional characteristics of NK cell subsets were detected by flow cytometry, and the correlation between NK cells and decompensation of liver function was analyzed. The frequency of circulating CD56^bright NK cells was significantly increased while circulating CD56^dim NK cells was significantly decreased in HBV-DLC patients as compared with HCs and HBV-CLC patients. Peripheral activated-CD56^bright NK cells from HBV-DLC patients might express lower levels of inhibitory receptor CD158b1/2 and higher levels of activating receptor NKG2D and their expression of perforin and granzyme A/B also increased significantly compared with HCs, suggesting a high immune activation status of peripheral CD56^bright NK cells in HBV-DLC patients. In HBV-DLC patients, the expression of CD107a and perforin in circulating CD56^dim NK cells was positively correlated with cytolytic capacity while CD107a and perforin expression in circulating CD56^dim NK cells were significantly decreased, suggesting an impaired cytolytic capacity of circulating CD56^dim NK cells. Besides, we found that the perforin expression of circulating CD56^dim NK cells correlated negatively with child-pugh classification in HBV-DLC patients. The functional properties of circulating NK cell subsets in HBV-DLC patients have changed significantly, especially of CD56^dim NK cells which closely related to decompensation of liver function. These findings may help provide new perspectives and theoretical basis for the treatment of patients with HBV-DLC.