Serum metabolic signatures of primary biliary cirrhosis and primary sclerosing cholangitis

Lauren N. Bell, Jacob Wulff, Megan Comerford, Raj Vuppalanchi, Naga Chalasani

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)263-274
Number of pages12
JournalLiver International
Volume35
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

Sclerosing Cholangitis
Biliary Liver Cirrhosis
Serum
Control Groups
Metabolome
Validation Studies
Physiologic Monitoring
Bile Acids and Salts
Lipid Metabolism
Lipid Peroxidation
Mass Spectrometry
Oxidative Stress
Biomarkers
Inflammation
Amino Acids
Therapeutics

Keywords

  • Bile acid metabolism
  • Cholestatic disease
  • Metabolome
  • Metabolomics

ASJC Scopus subject areas

  • Hepatology

Cite this

Serum metabolic signatures of primary biliary cirrhosis and primary sclerosing cholangitis. / Bell, Lauren N.; Wulff, Jacob; Comerford, Megan; Vuppalanchi, Raj; Chalasani, Naga.

In: Liver International, Vol. 35, No. 1, 01.01.2015, p. 263-274.

Research output: Contribution to journalArticle

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