Similarly, while upregulation of Sct signaling and Sct serum levels (observed in early-stage models of PBC and early-stage PBC patients) promotes DR, biliary damage and liver fibrosis [13], downregulation/loss of Sct expression/secretion (which leads to decreased bicarbonate secretion, “bicarbonate umbrella”) occurs in ductopenic diseases such as late-stage PBC [15, 21, 48]. Here, SCT is linked to primary biliary cholangitis.