Hypercholesterolemia of Cholestasis.

Cholesterol is a lipid of widespread physiologic and pathologic importance, whose homeostasis is tightly regulated through multiple mechanisms, including transport via low-density lipoprotein. Elevated serum low-density lipoprotein strongly correlates with the development of atherosclerotic cardiovascular disease. Cholestatic liver diseases, such as primary biliary cholangitis (PBC), are associated with impaired cholesterol homeostasis. The pathophysiology of hypercholesterolemia of PBC involves defective hepatocyte cholesterol clearance, downregulation of bile synthesis, and increased cholesterogenesis. Lipoprotein X is a highly specific biomarker for cholestasis and, in rare cases, contributes to serum total cholesterol levels >1000 mg/dL. The extent of hypercholesterolemia in PBC is associated with worse liver-related outcomes; nevertheless, patients with PBC do not have increased risk for atherosclerotic cardiovascular disease. Cardiovascular risk stratification of patients with PBC is most accurately achieved by direct measurement of apolipoprotein B, the protein component of pro-atherosclerotic lipoproteins involved in cholesterol transport. First and second line therapies for the treatment of hypercholesterolemia in cholestatic liver disease are statins and proprotein convertase subtilisin/kexin type 9 inhibitors, respectively. Apolipoprotein B level should be rechecked periodically to measure therapeutic response.