MON-286 - Extreme Hypercholesterolemia in AMA-Negative Primary Biliary Cirrhosis

BACKGROUND
Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease frequently associated with dyslipidemia, typically manifesting as mild to moderate hypercholesterolemia. In rare cases, however, extreme elevations in total cholesterol and calculated low-density lipoprotein cholesterol (LDL-C) may occur, creating diagnostic uncertainty and concern for primary hyperlipidemias and markedly increased cardiovascular risk. We report a case of severe hypercholesterolemia in a 49-year-old woman with AMA-negative PBC, complicated by autoimmune diabetes and pseudohyponatremia, in whom treatment of the underlying cholestatic process resulted in dramatic normalization of lipid parameters without lipid-directed therapy.

CASE PRESENTATION
The patient initially presented with acute metabolic decompensation characterized by severe hyperglycemia, profound hypercholesterolemia and marked hyponatremia. Lipid panel from this time showed total cholesterol 2378 mg/dL, hypertriglyceridemia of 1289 mg/dL, incalculable LDL due to severe hypertriglyceridemia and HDL of 135 mg/dL. Further evaluation revealed autoimmune diabetes and pseudohyponatremia attributable to extreme hyperlipidemia. Concurrently, she was found to have persistently elevated cholestatic liver enzymes and liver biopsy ultimately confirmed AMA-negative PBC. Given transaminitis and medication intolerance, lipid-lowering therapies were deferred. She was initiated on ursodeoxycholic acid and later elafibranor, resulting in significant improvement in liver enzymes, nutritional status, and lipid parameters, with total cholesterol decreasing to approximately 200 mg/dL and apolipoprotein B declining from 380 mg/dL to 75 mg/dL.

DISCUSSION
This case highlights severe hypercholesterolemia likely secondary to cholestasis-associated lipoprotein-X accumulation, a non-atherogenic mechanism that may mimic primary hyperlipidemia on standard lipid panels. Recognition of this entity is critical to avoid misclassification of cardiovascular risk and unnecessary escalation of lipid-lowering therapy. Multidisciplinary collaboration between endocrinology and hepatology is essential for accurate diagnosis and optimal management.

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