S3335 Cholesterol Chaos: The Elusive Lipoprotein X in Severe Cholestasis

Introduction: Cholestasis classically causes elevated liver enzymes, but rarely also causes elevated cholesterol. Biliary stasis prevents normal cholesterol metabolism, leading to accumulation in the blood. While uncommon, high serum cholesterol can cause pseudohyponatremia or hyperviscosity syndrome. More specifically, serum lipoproteins formed in the context of cholestasis often have an atypical composition which carries important clinical implications. Knowing how to interpret serum sodium, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in the setting of cholestasis is imperative as usual treatment paradigms may be inappropriate. Case Description/Methods: A 60-year-old woman with type II diabetes presented with 2 weeks of abdominal pain and jaundice. She was found to have low serum sodium 117 mmol/L but elevated serum osmolality 300 mOsm/kg. Her liver function tests were elevated in a cholestatic pattern with total bilirubin 21.5 mg/dL. Obtained as part of her hyponatremia workup, a cholesterol panel revealed TC 1141 mg/dL and LDL-C 1036 mg/dL. One month prior, her TC was 285 mg/dL and LDL-C was 159 mg/dL. Serologies were negative, and a right upper quadrant ultrasound did not show cholecystitis but did demonstrate cholelithiasis, presumed to be the etiology of her symptoms. Elevated cholesterol levels were deemed the culprit for her low sodium, confirming pseudohyponatremia. Serum apolipoprotein B (apoB) was 163 mg/dL, elevated but not to the same degree as measured LDL-C, suggestive of the presence of lipoprotein X (LpX) and thus lipid-lowering therapy was not initiated. Discussion: Cholestasis inhibits lecithin-cholesterol acyltransferase (LCAT), preventing cholesterol esterification and excretion. Instead, phospholipids (PL) and free cholesterol (FC) migrate into the blood and conglomerate to form LpX. Although LDL-C and LpX have a similar density, allowing LpX to be mistaken for LDL-C, distinguishing the 2 is important. Unlike LDL-C, LpX does not contain apoB and is not atherogenic. Direct measurement of LpX is not widely available, and detection relies on surrogate markers such as serum apoB or the FC: cholesterol ester (CE) ratio. Normal or mild elevation of apoB, particularly if discordant from the degree of LDL-C elevation, suggests the presence of LpX, as does an elevated FC:CE ratio. In cases of cholestasis with suspected LpX elevation, it is recommended to defer decisions regarding lipid-lowering therapy until cholestasis resolves and studies are repeated.