In this context it could be speculated that destruction of intrahepatic bile ducts or the appearance of aberrant cholangiocytes has initially stimulated the intrahepatic NK cells, leading to cholangiocyte killing and apoptosis by the granzyme/perforin pathway or by activation of death receptors belonging to the tumor necrosis factor (TNF) receptor superfamily and TRAIL, as it was reported in the bile duct-ligated mice [27] and in patients with the primary biliary cirrhosis, where the activation of hepatic NK cells led to exacerbated damage on liver tissues [23, 28, 29]. Here, PRF1 is linked to primary biliary cholangitis.