Publication
A novel serum metabolomic panel distinguishes IgG4‐related sclerosing cholangitis from primary sclerosing cholangitis
Publisher:
Wiley
Date:
21-02-2022
DOI:
10.1111/LIV.15192
Abstract: Primary sclerosing cholangitis (PSC) and IgG4‐related sclerosing cholangitis (IgG4‐SC) are chronic fibro‐inflammatory immune‐mediated hepatobiliary conditions that are challenging to distinguish in a clinical setting. Accurate non‐invasive biomarkers for discriminating PSC and IgG4‐SC are important to ensure a correct diagnosis, prompt therapy and adequate cancer surveillance. We performed nuclear magnetic resonance (NMR)‐based metabolomic profiling using serum s les collected prospectively from patients with PSC ( n = 100), IgG4‐SC ( n = 23) and healthy controls (HC n = 16). Multivariate analysis of the serum metabolome discriminated PSC from IgG4‐SC with greater accuracy (AUC 0.95 [95%CI 0.90–0.98]) than IgG4 titre (AUC 0.87 [95%CI 0.79–0.94]). When inflammatory bowel disease (IBD) was excluded as a comorbid condition (IgG4‐SC n = 20, PSC n = 22), the diagnostic AUC increased to 1.0, suggesting that the metabolome differences identified are not a result of the increased prevalence of IBD in PSC relative to IgG4‐SC patients. Serum lactate ( p .0001), glucose ( p .01) and glutamine ( p .01) metabolites were increased in IgG4‐related disease (IgG4‐RD) and IgG4‐SC in iduals compared to PSC, whereas mobile choline ( p .05), 3‐hydroxybutyric acid ( p .01) and ‐CH 3 lipoprotein resonances ( p .01) were decreased. Taken together, serum metabolomic profiling has the potential to be incorporated as a diagnostic criterion, independent of IgG4 titre, to improve the diagnosis of IgG4‐RD and help distinguish IgG4‐SC from PSC.