*Lipoprotein X hyperlipidemia and Its Complications in a Patient with Primary Sclerosing Cholangitis

Abstract

Lead Author's Financial Disclosures Nothing to disclose. Study Funding None. Background/Synopsis We reviewed a case of a young man referred for management of severe hypercholesterolemia and bilateral palpebral xanthelasma. This is intended to highlight key features in diagnosis and management of severe hypercholesterolemia due to LpX from biliary obstructive disease. Objective/Purpose To review clinical management of severe hypercholesterolemia due to LpX. Methods Clinical management at tertiary care lipid program. Results A 22-year-old slim male with history of Wilson's disease, Crohn's disease, and primary sclerosing cholangitis (PSC) was referred for management of severe hypercholesterolemia and progressive symmetric palpebral xanthelasmas. There is no family history of severe hypercholesterolemia or premature atherosclerotic cardiovascular disease (ASCVD), nor were any other secondary causes identified. He was successfully treated with cholestyramine for pruritis which resulted in marked total cholesterol reduction and increased triglyceride (TG) level. Conclusions Very severe hypercholesterolemia with total cholesterol levels >500 mg/dL is a rare condition. Levels this high are typically associated with homozygous familial hypercholesterolemia (FH) due to an increased level of atherogenic LDL cholesterol (LDL-C). However, other causes need to be considered in the right clinical context, such as lipoprotein fraction lipoprotein X (LpX) in an individual with obstructive biliary disease. LpX is a consequence of ``spillover'' of hepatic free cholesterol (FC)/phospholipid complexes in disc- shaped lipoproteins which do not contain apoB. Consequently, there is wide discordance between apoB and the calculated LDL-C and high serum FC levels. The diagnosis is typically made in the right clinical context without FC measurement since this test is not commercially available. Hypercholesterolemia due to LpX is not associated with increased ASCVD risk, but its presence can be a marker of the severity of liver disease and cause other medical complications including hyperviscosity syndrome, pulmonary embolism and cholesteroloma.Our patient's marked increase in total cholesterol without severe increase in apoB suggested progression of PSC and prompted referral back to his primary Hepatology team. Additional cholesterol-lowering pharmacotherapy is not indicated for hypercholesterolemia due to LpX without hyperviscosity. Nothing to disclose.