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Serum metabolic signatures of primary biliary cirrhosis and primary sclerosing cholangitis
Author(s) -
Bell Lauren N,
Wulff Jacob,
Comerford Megan,
Vuppalanchi Raj,
Chalasani Naga
Publication year - 2015
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12680
Subject(s) - primary biliary cirrhosis , primary sclerosing cholangitis , gastroenterology , medicine , lipid metabolism , disease
Background & Aims A greater understanding of cholestatic disease is necessary to advance diagnostic tools and therapeutic options for conditions such as primary biliary cirrhosis ( PBC ) and primary sclerosing cholangitis ( PSC ). The purpose of this study was to determine and compare the serum metabolomes of patients with PBC ( n = 18) or PSC ( n = 21) and healthy controls ( n = 10) and to identify metabolites that may differentiate these two cholestatic diseases. Methods and Results Using a mass spectrometry‐based, non‐targeted biochemical profiling approach, we identified 420 serum metabolites, 101 that differed significantly ( P ≤ 0.05) between PBC and control groups, 115 that differed significantly between PSC and control groups, and 56 that differed significantly between PSC and PBC groups. Random forest classification analysis was able to distinguish patients with PBC or PSC with 95% accuracy with selected biochemicals reflective of protein and amino acid metabolism identified as the major contributors. Metabolites related to bile acid metabolism, lipid metabolism, inflammation, and oxidative stress/lipid peroxidation were also identified as differing significantly when comparing the disease groups and controls, with some of these pathways differentially affected in the PBC and PSC groups. Conclusion In this study, we identified novel metabolic changes associated with cholestatic disease that were both consistent and different between PBC and PSC . Validation studies in larger patient cohorts are required to determine the utility of these biochemical markers for diagnosis and therapeutic monitoring of patients with PBC and PSC .