Metabolism of cholesterol and low- and high-density lipoproteins in primary biliary cirrhosis: cholesterol absorption and synthesis related to lipoprotein levels and their kinetics*1, *2

Abstract

Cholesterol absorption, elimination, and synthesis, and low-density lipoprotein (LDL) and high density lipoprotein (HDL) kinetics were studied in patients with mild to severe primary biliary cirrhosis (PBC) (n = 16) to show how this cholestatic disease modified cholesterol and lipoprotein metabolism as compared with healthy controls (n = 50). Serum total and lipoprotein cholesterol and triglyceride levels were similar in the two groups, but in PBC, especially in severe forms, very low density lipoprotein (VLDL) was rich in apoprotein (apo) B and cholesterol and low in triglycerides, whereas LDL was rich in triglycerides and low in esterified cholesterol, and HDL was enriched by surface lipids, phospholipids, and free cholesterol. In severe PBC, the fractional catabolic rate (FCR) for LDL apo B was reduced. The transport rate (TR) for LDL apo B was unaffected and it tended to correlate with the LDL apo B and LDL cholesterol levels in PBC, whereas in the controls the LDL apo B concentration was regulated by both the FCR and TR, and LDL cholesterol was regulated only by FCR. FCR for apo A-I in HDL was unaltered in PBC, but TR for apo A-I was reduced in the severe cases. Cholesterol absorption efficiency was significantly reduced in PBC (14.5 +/- 3.0% in severe PBC and 34.0 +/- 2.5% in mild PBC vs. 47.4 +/- 1.4% in the controls, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperlipidemia in the Setting of Primary Biliary Cholangitis: A Case Report and Review of Management Strategies

“…PBC is a chronic and progressive cholestatic autoimmune liver disease. Its characteristic is the destruction of intrahepatic bile ducts with portal inflammation and scarring [1]. In the setting of cholestasis, there is a reduction in bile acid production and, consequently, decreased intestinal absorption of cholesterol.…”

“…In the healthy liver, lecithin-cholesterol acyltransferase converts the free cholesterol in Lp-X into the cholesterol esters found in LDL. The reduced function of lecithin cholesterol acyltransferase in PBC results in changes in lipoprotein composition, decreased LDL, and increased Lp-X [1]. Lp-X protects endothelial cells and delays atherosclerosis by preventing LDL oxidation.…”

“…Primary biliary cholangitis (PBC) is a condition that predisposes patients to increased endogenous production of cholesterol [1]. It is, therefore, important to closely monitor them and actively treat their dyslipidemia [2].…”

Dyslipidemia and its features in primary biliary cholangitis

“…Недостаточное поступление желчных кислот в кишечник при ПБХ ухудшает солюбилизацию пищевого холестерина и образование мицелл, что приводит к снижению его всасывания из кишечника. Через систему обратной связи стимулируется внутрипеченочный синтез холестерина и снижается захват печенью липопротеинов низкой плотности (ЛПНП) через их рецепторы [13]. Повышенный синтез холестерина в печени приводит к увеличению его уровня в крови.…”