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Hypercholesterolemia and atherosclerosis in primary biliary cholangitis (primary biliary cirrhosis)

Steven Flamm, MD
Andre A Kaplan, MD
Raoul Poupon, MD
Sanjiv Chopra, MD, MACP
Section Editor
Keith D Lindor, MD
Deputy Editor
Kristen M Robson, MD, MBA, FACG


Hypercholesterolemia is a common feature of primary biliary cholangitis (PBC; previously referred to as primary biliary cirrhosis) and other forms of cholestatic liver disease. The mechanism of hyperlipidemia in cholestatic disorders is different from that in other conditions as unusual lipoprotein particles, such as lipoprotein X, may accumulate and levels of HDL cholesterol are typically elevated. An important question is whether these patients are at risk for the complications of hypercholesterolemia? The available data suggest that patients with PBC and hypercholesterolemia are not at increased risk of atherosclerosis. However, patients with early stage PBC may have independent abnormalities of lipid metabolism and may be exposed to increased cardiovascular risk due to their normal life expectancy under ursodeoxycholic acid (UDCA) treatment. If there is any question, PBC patients should have fasting lipoprotein profiles and assessment of concomitant risk factors for atherosclerosis.

This topic will review hypercholesterolemia and atherosclerosis in patients with primary biliary cholangitis. Other issues related to hypercholesterolemia and the role of hypercholesterolemia in the development of atherosclerosis are discussed separately. (See "Screening for lipid disorders in adults" and "Overview of established risk factors for cardiovascular disease" and "Pathogenesis of atherosclerosis" and "Management of low density lipoprotein cholesterol (LDL-C) in secondary prevention of cardiovascular disease".)


Initial studies suggested that the total plasma cholesterol was elevated in 50 percent of patients with PBC using normal values that ranged from 218 mg/dL to 300 mg/dL (5.7 to 7.9 mmol/L) [1]. The mean plasma cholesterol concentrations in this study were 285 mg/dL (7.4 mmol/L) in asymptomatic patients and 377 mg/dL (9.8 mmol/L) in symptomatic patients. Later studies confirmed these findings; 76 percent and 96 percent of asymptomatic and symptomatic patients had total plasma cholesterol values above 200 mg/dL (5.2 mmol/L), respectively [2-4]. However, the range of values was extremely wide, from 120 mg/dL (3.1 mmol/L) to 1775 mg/dL (46.1 mmol/L) in one report of 284 patients [5].


Some studies have found elevated very low density lipoprotein (VLDL) and low density lipoprotein (LDL) levels, as well as markedly elevated high density lipoprotein (HDL) levels in some patients with early (histologic) stage PBC [4,5]. In later stage disease, the LDL levels increased further, but HDL levels fell markedly. A larger study reached similar conclusions: both LDL and total cholesterol levels increased with worsening histologic stage; the levels of HDL and apolipoprotein A-1, which is associated with HDL, were elevated at all stages but fell in patients with cirrhosis (though they may still be elevated compared with age-matched controls) [3]. Triglyceride levels were normal or slightly elevated.

Some of the excess LDL in PBC is composed of an abnormal lipoprotein particle (lipoprotein X), which is seen in advanced cholestatic liver disease and marked hyperbilirubinemia [6]. It is rich in free cholesterol and phospholipids [3,5,7]. Lipoprotein X is believed to reduce the atherogenicity of LDL cholesterol by preventing LDL oxidation [8]. Prolonged LDL oxidation has been demonstrated in patients with PBC, and normalizes following liver transplantation [6].

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Literature review current through: Sep 2017. | This topic last updated: Oct 15, 2015.
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