Multidisciplinary Management of Lipoprotein X-Induced Hyperlipidemia Secondary to Drug-Induced Liver Injury

Background/Synopsis

A 72-year-old woman presents with pruritis, jaundice, skin lesions, blurred vision, and facial droop. Blood work reveals a total bilirubin of 21.5 mg/dL (15.4 mg/dL direct, 6.1 mg/dL indirect), AST 388 U/L, ALT 444 U/L, alkaline phosphatase 1,900 U/L, sodium 119 mmol/L, total cholesterol >1350 mg/dL, HDL 7 mg/dL, and triglycerides 306 mg/dL; LDL cannot be calculated. Brain magnetic resonance imaging demonstrates no acute pathology. Viral and autoimmune serologies are negative. Magnetic resonance cholangiopancreatography demonstrates no biliary pathology.

She reports drinking various herbal tea preparations along with an unknown supplement she purchased on television. A liver biopsy demonstrates bile duct injury and centrilobular cholestasis most consistent with drug-induced liver injury. She is treated with ursodiol and bile acid sequestrants however has ongoing symptoms. Her serum viscosity level is elevated and additional testing detects lipoprotein X. She is treated with three rounds of plasma exchange with normalization of her sodium level, resolution of xanthomas and neurologic symptoms, and marked improvement in her lipid panel.

Objective/Purpose

Recognize sequelae of lipoprotein X accumulation including pseudohyponatremia, xanthomas, and hyperviscosity. Discuss multidisciplinary management of lipoprotein X-induced hyperlipidemia.

Methods

Clinical case management at a tertiary care lipid program.

Results

Lipoprotein-X induced hyperlipidemia is a rare lipoprotein disorder. The most common etiologies are cholestatic liver disease, lecithin:cholesterol acyltransferase (LCAT) deficiency, liver graft-versus-host disease, and lipid infusions. With cholestasis, bile excretion and synthesis are inhibited to prevent bile-induced hepatotoxicity. This results in lack of cholesterol excretion into bile and free cholesterol release into blood, where it merges with phospholipids, albumin, and apolipoproteins C and E, to form lipoprotein X. As lipoprotein X does not contain apolipoprotein B, it does not undergo hepatic clearance and its levels are not affected by lipid-lowering therapies such as statins. Lipoprotein X has a similar density to LDL and can lead to false elevations in LDL on standard lipid panels, therefore lipoprotein electrophoresis can be used to detect lipoprotein X.

Hyperlipidemia induced by lipoprotein X accumulation can lead to numerous clinical sequelae including xanthomas, pseudohyponatremia, and hyperviscosity syndrome with associated neurologic symptoms. The mainstay of therapy is treatment of the underlying cholestatic disorder, however with refractory symptoms therapeutic plasma exchange can provide rapid lipoprotein clearance.

Conclusions

Due to lack of LDL receptor-mediated hepatic clearance, traditional lipid-lowering therapies do not have a role in the management of lipoprotein X-induced hyperlipidemia. When symptoms persistent despite treatment of underlying cholestatic disorder, therapeutic plasma exchange can be utilized for lipoprotein clearance.