Apoptosis of hepatocytes is mediated in cholestasis through the cell surface molecule FAS.29,37–39 Ligand binding to the FAS receptor on hepatocytes induces caspase 8 activation that initiates the FAS-mediated pathway of apoptotic cell death.40 To determine whether the evidence of FAS-mediated apoptosis is present in PNAC, we first measured the hepatic expression of Fas in 14 days DSS-PN and chow mice and showed increased Fas mRNA and FAS protein were associated with cholestasis in DSS-PN mice (Figure 1A, B). Here, CASP8 is linked to cholestasis.