In a previous section (see Section 2.2), we have already introduced a number of concepts that are critical in analyzing the contribution of different HIFs to fibrogenic CLD progression, including two major issues: (i) HIF-1α (then HIF1) is ubiquitously expressed, practically in all tissues, whereas HIF-2α (then HIF2) is more selectively expressed in defined cell types, including hepatocytes; and (ii) both HIF-α subunits respond to hypoxia but their transcriptional gene targets, oxygen dependence and kinetics of activation differ substantially. The gene discussed is EPAS1; the disease is congenital secretory chloride diarrhea 1.