Hypercholesterolemia After COVID-19: Time to Include Lipoprotein X Among the Differential Diagnoses

Lipoprotein X (LpX) is an abnormal lipoprotein composed of phospholipids, free cholesterol, and albumin. Its overaccumulation is an infrequent cause of hyperlipidemia, which oftentimes presents in patients with cholestatic liver disease. The aim is to present the first 2 cases of patients with post-COVID cholangiopathy and LpX overaccumulation.

We present 2 female patients (ie, a 34-year-old [patient 1] and a 56-year-old [patient 2]), who had complicated courses of COVID-19, requiring prolonged mechanical ventilation (>4 weeks). One month after discharge, patient 1 presented with abdominal pain. Patient 2 had gangrenous cholecystitis and later developed recurrent elevation of alkaline phosphatase and bilirubin. Both patients were diagnosed with cholestatic liver disease. During outpatient follow-up both patients were found to have elevated plasma low-density lipoprotein cholesterol (LDL-C) in routine lipid panels (723 mg/dL and 1389 mg/dL, respectively). Both patients underwent various treatments for elevated LDL-C before referral to endocrinology. Patients were diagnosed with LpX overaccumulation from post-COVID-19 cholangiopathy. In both patients, LDL-C fluctuations seen in routine lipid panels (affected by LpX levels) were tightly correlated with changes in alkaline phosphate and bilirubin.

Our patients represent the first report of LpX overaccumulation in patients with post-COVID-19 cholangiopathy. Whether LpX accumulation is only the result of liver dysfunction, or COVID-19 infection plays a direct role in elevated LpX levels is still unknown.

In patients with complicated courses of COVID-19, LpX overaccumulation should be considered when a routine lipid panel shows significant LDL-C elevations. Awareness among health care providers regarding LpX is important to avoid unnecessary workup and treatment.