Biochemical exploration of cholestasis: interpretation, traps and interferences

We described the case of a 33-year-old patient who presented to the emergency department with non-febrile jaundice associated with epigastric pain. He suffered from acute non-severe alcoholic hepatitis and cholestasis. Biochemical investigations highlighted a huge elevation of the alpha-1-globulins fraction with an unexpected peak in the alpha-1-globulins area in serum protein electrophoresis, a severe hypercholesterolemia without xanthelasmas nor cholesterolomas. Investigations revealed an abnormal lipoprotein, Lipoprotein X (LpX) that can be responsible for the hypercholesterolemia, but also interferes with biochemical tests like direct low-density lipoprotein cholesterol, albumin, and serum electrolytes assays. LpX is an abnormal lipoprotein, which can be present in patients with liver dysfunction, notably in cholestasis-related conditions where the metabolism of plasma lipoproteins is altered. Cholestasis prevents the normal formation of bile acids, leading to the formation of LpX, which is rich in phospholipids and unesterified cholesterol, but poor in esterified cholesterol, triglycerides and proteins. The accumulation of LpX can lead to severe hypercholesterolemia, but this remains uncommon and data regarding the pathophysiology and incidence of this disease is scarce. The laboratory investigation of patients with suspected Lpx can be challenging, due to the lack of available methods for measurement of LpX. In conclusion, LpX-induced hyperlipidemia must be identified to prevent interference in results for a number of biochemical tests, and additionally to improve patient care.