A NEW study highlights distinctive changes in blood lipids that could offer fresh insight into the biology of primary biliary cholangitis (PBC), and potentially open doors to improved diagnostics and treatments for the chronic autoimmune liver disease.
Researchers from several Polish medical centres analysed the plasma sphingolipid profiles of 45 patients with early-stage PBC who were undergoing standard treatment with ursodeoxycholic acid. Their results were compared with samples from 30 healthy individuals. Using advanced ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS), the team uncovered a pattern of sphingolipid disruptions that appear closely tied to inflammation, immune imbalance, and early fibrotic changes in the liver.
Sphingolipid patterns tied to primary biliary cholangitis
The clearest shift involved an overall reduction in total sphingolipid levels among PBC patients. This decline was particularly pronounced in key phosphorylated molecules, including sphingosine-1-phosphate (S1P) and sphinganine-1-phosphate (SPA1P), lipids known to regulate immune responses and vascular function. These reductions also correlated with portal hemodynamic abnormalities, as measured by Doppler ultrasound, hinting at a possible role in the circulatory disturbances commonly seen in cholestatic liver disease.
Study links ceramides to primary biliary cholangitis
Conversely, levels of C18:1-ceramide were elevated in the PBC group. This specific ceramide subtype showed a trend toward association with increased liver stiffness, a marker suggestive of advancing fibrosis. Meanwhile, very-long-chain ceramides, which may have protective metabolic roles, were reduced.
The study also revealed several important links between lipid disturbances and inflammatory markers. Notably, sphingosine levels were positively correlated with interleukin-6, a cytokine involved in chronic inflammation and autoimmune processes. Such associations reinforce the idea that sphingolipids are not merely bystanders but may actively contribute to the cascade of immune dysregulation and tissue remodelling that drives PBC.
According to the authors, these findings point to a selective, disease-specific pattern of sphingolipid alterations in early PBC. While further research is needed, the results suggest that certain sphingolipids could serve as biomarkers of disease activity or even as therapeutic targets, offering a new angle in the management of cholestatic liver disorders.
Reference
Rogalska M et al. Altered sphingolipid profile in primary biliary cholangitis: associations with fibrosis and inflammation. Sci Rep. 2025; 15:42502.
