Free fatty acid remodeling in early-stage primary biliary cholangitis

Primary biliary cholangitis (PBC) features established systemic lipid disturbances, yet alterations in bioactive free fatty acids (FFA) are incompletely characterized. This study aimed to evaluate the plasma FFA profile and estimated fatty acid metabolism indices in patients with early-stage PBC. The study included 61 patients with early-stage PBC and 46 healthy controls. Plasma FFA fraction was isolated by thin-layer chromatography and quantified via gas-liquid chromatography/flame ionization detection. Product-to-precursor ratios estimated desaturase and elongase activities. Liver fibrosis was assessed non-invasively using AST-to-platelet ratio index (APRI), Fibrosis-4 index (FIB-4), and point shear-wave elastography. Total plasma FFA concentrations were significantly elevated in the PBC group (819.32 ± 289.18 µM vs. 651.63 ± 212.82 µM; P < 0.001). Saturated fatty acid (SFA) levels remained comparable between groups. The expansion of FFA pool was driven by monounsaturated fatty acids (MUFA) - specifically palmitoleic (C16:1 n-7) and oleic (C18:1 n-9) acids - and early n-6 pathway polyunsaturated fatty acids (PUFA). The n-6/n-3 PUFA ratio was elevated ( P = 0.008), while arachidonic acid levels remained unchanged. Estimated stearoyl-CoA desaturase-1 (SCD1) indices were elevated, whereas elongase 6 (ELOVL6) indices were reduced. Palmitoleic acid correlated positively with hepatocellular injury markers and emerged as an independent predictor of fibrosis severity (FIB-4) in multivariable regression (β = 0.305, P = 0.005). Early-stage PBC is characterized by marked fatty acid homeostasis disturbances, featuring MUFA and early n-6 PUFA accumulation. This profile indicates coordinated C16-C18 axis remodeling. Increased levels of both palmitoleic acid (C16:1 n-7) and oleic acid (C18:1 n-9) indicate prominent MUFA remodeling in early-stage PBC, with palmitoleic acid additionally associated with fibrosis-related indices. These findings support the potential value of plasma FFA profiling in improving early recognition of disease-related metabolic disturbances.