Acylcarnitine and Free Fatty Acid Profiles in Primary Biliary Cholangitis: Associations with Fibrosis and Inflammation

Abstract

Background: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by bile duct destruction, cholestasis, and fibrosis. Acylcarnitines are esters of carnitine responsible for the transport of long-chain fatty acids into mitochondria for β-oxidation, playing a crucial role in energy metabolism and lipid homeostasis. This study aimed to assess acylcarnitine and free fatty acid (FFA) profiles in PBC patients and their associations with fibrosis severity and inflammation. Methods: This cross-sectional study included 46 PBC patients and 32 healthy controls. Acylcarnitines and FFAs were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and enzymatic assays, respectively. Liver stiffness was measured by point shear wave elastography (ElastPQ), and fibrosis was assessed using APRI and FIB-4 scores. Inflammatory markers (IL-6, IL-1β) were also analyzed. Results: PBC patients had significantly higher levels of C18:1-acylcarnitine (median: 165.1 ng/mL) compared with the controls (152.4 ng/mL, p = 0.0036). Similarly, the FFA levels were markedly elevated in the PBC patients (median: 0.46 mM/L) compared with the controls (0.26 mM/L, p < 0.0001). Patients with higher liver stiffness (ElastPQ > 5.56 kPa) had significantly elevated C18:1-acylcarnitine (p = 0.0008) and FFA levels (p = 0.00098). Additionally, FFAs were significantly increased in patients with higher APRI and FIB-4 scores and were associated with elevated inflammatory markers (IL-6, IL-1β) and liver injury markers. Multivariate regression analysis confirmed C18:1-acylcarnitine (OR = 1.031, 95% CI: 1.007-1.057, p = 0.013) and FFAs (OR = 2.25 per 0.1 mM/L increase, 95% CI: 1.20-4.22, p = 0.012) as independent predictors of fibrosis severity in PBC. Conclusions: C18:1-acylcarnitine and FFAs are significantly elevated in PBC and are strongly associated with fibrosis severity and inflammation. These findings suggest a link between lipid metabolism disturbances and PBC. Both metabolites may potentially serve as non-invasive biomarkers of fibrosis progression in PBC, warranting further investigation.

Keywords: acylcarnitines; bile acids; fibrosis; free fatty acids; inflammation; liver stiffness; metabolic biomarkers; mitochondrial dysfunction; primary biliary cholangitis; β-oxidation.

Figure 1

C18:1-carnitine in PBC group and control group. C18:1-carnitine concentrations were significantly elevated in patients with PBC compared with the healthy controls (p = 0.0036).

Figure 2

Free fatty acids in PBC group and control group. Free fatty acid levels were markedly elevated in patients with PBC compared with the healthy controls (p < 0.0001).

Figure 3

Lipid metabolism parameters stratified by fibrosis markers. C18:1-carnitine levels were significantly higher in patients with ElastPQ > 5.56 kPa compared with those with lower ElastPQ values (p = 0.0008). Similarly, the free fatty acid (FFA) levels were markedly elevated in patients with higher ElastPQ measurements (p = 0.00098) and differed significantly when stratified by the FIB-4 (p = 0.0207) and APRI (p = 0.0237) cutoffs. These findings support an association between altered lipid metabolism and increased liver stiffness/fibrosis in PBC.

Figure 4

ROC curve for C18:1-carnitine as a predictor of significant liver fibrosis (ElastPQ > 5.56 kPa) in PBC. The optimal cutoff of 193.87 ng/mL was determined based on the highest Youden index (0.48), maximizing specificity (87.0%) while maintaining moderate sensitivity (60.9%). Blue line—ROC curve, red line—baseline, green line—optimal cutoff (Youden index).

Figure 5

ROC curve for FFA (mM/L) as a predictor of significant liver fibrosis (ElastPQ > 5.56 kPa) in PBC. The optimal cutoff of 0.33 mM/L was determined based on the highest Youden index (0.43), balancing high sensitivity (87.0%) with moderate specificity (56.5%). Blue line—ROC curve, red line—baseline, green line—optimal cutoff (Youden index).