Small dense low-density lipoprotein in primary biliary cholangitis: Independent association with metabolic syndrome

Figure 1 Distribution of ln-transformed small dense low-density lipoprotein levels according to metabolic syndrome status. Ln (small dense low-density lipoprotein) levels were significantly higher in patients with metabolic syndrome than in those without metabolic syndrome (P = 0.004, Mann-Whitney U test). Boxplots represent median values, interquartile ranges, and whiskers. sdLDL: Small dense low-density lipoprotein.

Figure 2 Multivariable linear regression analysis of factors associated with ln-transformed small dense low-density lipoprotein levels. Error bars represent 95% confidence interval. Metabolic syndrome remained independently associated with higher ln (small dense low-density lipoprotein) levels after adjustment for age, sex, body mass index, and lipid-lowering therapy. BMI: Body mass index; CI: Confidence interval.

Figure 3 Receiver operating characteristic analysis of lipoprotein-related parameters for identification of metabolic syndrome. Receiver operating characteristic curves are shown for small dense low-density lipoprotein (sdLDL), low-density lipoprotein (LDL)-C, large LDL, and sdLDL/LargeLDL ratio. The sdLDL/LargeLDL ratio demonstrated the highest discriminatory performance, whereas LDL-C and large LDL showed inverse discriminatory patterns. Curves for LDL-C and large LDL fall below the diagonal reference line, indicating that lower values of these parameters were associated with metabolic syndrome. sdLDL: Small dense low-density lipoprotein; ROC: Receiver operating characteristic; MetS: Metabolic syndrome; LDL: Low-density lipoprotein; PBC: Primary biliary cholangitis.

Figure 4 Mechanistically distinct lipid remodeling pathways in primary biliary cholangitis. Left panel: Cholestasis impairs bile acid secretion and disrupts biliary phospholipid transport, leading to reflux of phospholipids and free cholesterol into the circulation and reduced lecithin-cholesterol acyltransferase activity. These alterations promote the formation of lipoprotein X, a phospholipid-rich, apolipoprotein B (ApoB)-deficient particle that contributes to hypercholesterolemia but does not reflect classical ApoB-driven atherogenic dyslipidemia. Right panel: In contrast, insulin resistance associated with metabolic syndrome promotes hepatic overproduction of triglyceride-rich very low-density lipoprotein 1 particles. Subsequent cholesteryl ester transfer protein-mediated lipid exchange and hepatic lipase-dependent remodeling generate small dense low-density lipoprotein (sdLDL), an ApoB-containing lipoprotein subfraction characterized by prolonged circulation time, increased oxidative susceptibility, and enhanced arterial wall penetration. These pathways are mechanistically distinct and support the concept that sdLDL levels in primary biliary cholangitis primarily reflect superimposed metabolic dysfunction rather than intrinsic cholestatic activity. Created by the authors for illustrative purposes (OpenAI 1.3.2026). LCAT: Lecithin-cholesterol acyltransferase; LpX: Lipoprotein X; PBC: Primary biliary cholangitis; sdLDL: Small dense low-density lipoprotein; LDL: Low-density lipoprotein; VLDL: Very low-density lipoprotein; ApoB: Apolipoprotein B; CETP: Cholesteryl ester transfer protein; TG: Triglycerides.