Metabolomic profiles differentiate between Porto-Sinusoidal Vascular Disorder, Cirrhosis, and Healthy Individuals

Abstract

Porto-sinusoidal vascular disorder (PSVD) is a rare and diagnostically challenging vascular liver disease. This study aimed to identify distinct metabolomic signatures in patients with PSVD or cirrhosis to facilitate non-invasive diagnosis and elucidate perturbed metabolic pathways.

Highlights

• We identified distinct metabolic signatures that discriminate PSVD from cirrhosis and healthy controls
• A computational biology approach revealed alterations in the pyrimidine, glycine, serine and threonine pathways exclusively in patients with PSVD.
• A machine learning-derived signature could reliably distinguish PSVD from healthy controls or cirrhosis using 4 to 6 metabolites.
• These metabolomic perturbations might characterize pathophysiologically relevant pathways in PSVD.
• Analyzing metabolomic profiles may allow for earlier non-invasive diagnosis of PSVD and guide diagnostic pathways.

Porto-sinusoidal vascular disorder (PSVD) is a vascular liver disease that can lead to pre-sinusoidal portal hypertension in the absence of cirrhosis, with poorly understood pathophysiology and no established treatment. Our study demonstrates that analyzing the serum metabolome could reveal distinct metabolic signatures in patients with PSVD, including alterations in the pyrimidine, glycine, serine and threonine pathways, potentially shedding light on the disease’s underlying pathways. These findings could enable earlier and non-invasive diagnosis of PSVD, potentially reducing reliance on invasive procedures like liver biopsy and guiding diagnostic pathways.