Metabolomics-based Investigation of Primary Biliary Cholangitis: A Cholestatic Liver Disease

Abstract

Introduction Primary Biliary Cholangitis (PBC) is a rare disease that affects the liver. It causes the progressive destruction of the intrahepatic bile ducts, leading to liver fibrosis. Currently, the diagnosis of PBC includes a medical and family history, physical exams, blood tests, imaging tests, and occasionally a liver biopsy. If not promptly treated, PBC progresses to cirrhosis, liver failure, and death. Objectives To improve the development of new diagnostic or prognostic methods for PBC, a metabolomic-based study was conducted to evaluate the metabolomic profiles reflected in plasma and urine samples from healthy individuals and PBC patients. This study aimed to gain a better understanding of the underlying pathological mechanisms of PBC. Methods Blood plasma and urine samples were collected from 30 female PBC patients and 20 female healthy controls. The study used an untargeted metabolomic approach involving liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS). The data was processed using multivariate and univariate statistical methods. Results Forty-seven plasma and fifty-six urine metabolites demonstrated statistical differences between PBC patients and healthy controls (p ≤ 0.05). The most significant differences were found in metabolites related to bile acid and lipid metabolism (including phospholipids and fatty acids) and branched-chain amino acids. These findings indicate that metabolomic profiling in plasma and urine can help identify new diagnostic biomarkers for PBC. Conclusions The study highlights metabolites linked to fatty acid beta-oxidation, bile acid biosynthesis, and amino acid metabolism as potential candidates for biomarkers in PBC, which can assist further studies for PBC diagnosis and therapeutic monitoring.