A recent study published in Scientific Reports found that patients with early-stage primary biliary cholangitis (PBC) who take ursodeoxycholic acid have altered expression of a group of molecules called sphingolipids.
Sphingolipids are a special class of fats that play a vital role in cell structure and signaling. Because sphingolipid expression is associated with immunity and inflammation, the researchers sought to investigate their role in disease activity.
The study included 45 individuals with PBC and 30 healthy controls. All participants underwent laboratory and imaging testing to measure fibrosis, liver function and sphingolipid expression.
Compared to the controls, patients with PBC had higher liver enzyme levels, markers of cholestasis, markers of inflammation and fibrosis indices. This indicates liver dysfunction and systemic inflammation in the PBC group.
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Overall, patients with PBC had a lower total concentration of sphingolipids than controls. In particular, the concentrations of sphinganine-1-phosphate (SPA1P) and sphingosine-1-phosphate were much lower in those with PBC. While levels of some ceramides (a type of sphingolipid) were significantly higher in participants with PBC than controls, others were much lower.
The study also found that higher sphingolipid concentrations were associated with lower levels of markers of liver fibrosis, cholestasis and liver cell damage. Additionally, higher sphingolipid levels were linked to increased albumin concentrations. Albumin is a protein produced by the liver to transport molecules throughout the body.
While C18:1-ceramide was most strongly associated with liver stiffness, the relationship was not statistically significant.
The researchers identified two main clusters of patients: those with high levels of medium- and long-chain ceramides (Cluster 1) and those with high levels of phosphorylated sphingolipids (Cluster 2). Participants in Cluster 1 tended to have more pro-inflammatory markers than individuals in Cluster 2. Patients in Cluster 2 had lower Fibrosis-4 scores than those in Cluster 1, though this difference did not achieve statistical significance.
“These findings highlight the relevance of sphingolipid remodeling in the pathophysiology of PBC and support further investigation into sphingolipids as potential biomarkers or therapeutic targets in cholestatic liver disease,” the authors concluded.
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