Metabolomic biomarkers are associated with mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis

Aim: To assess the ability of signature metabolites alone, or in combination with the model for end-stage liver disease-Na (MELD-Na) score to predict mortality in patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis. Materials & methods: Plasma metabolites were detected using ultrahigh-performance liquid chromatography/tandem mass spectrometry in 39 patients with cirrhosis caused by primary biliary cholangitis or primary sclerosing cholangitis. Mortality was predicted using Cox proportional hazards regression and time-dependent receiver operating characteristic curve analyses. Results: The top five metabolites with significantly greater accuracy than the MELD-Na score (area under the receiver operating characteristic curve [AUROC] = 0.7591) to predict 1-year mortality were myo-inositol (AUROC = 0.9537), N-acetylputrescine (AUROC = 0.9018), trans-aconitate (AUROC = 0.8880), erythronate (AUROC = 0.8345) and N6-carbamoylthreonyladenosine (AUROC = 0.8055). Several combined MELD-Na-metabolite models increased the accuracy of predicted 1-year mortality substantially (AUROC increased from 0.7591 up to 0.9392). Conclusion: Plasma metabolites have the potential to enhance the accuracy of mortality predictions, minimize underestimates of mortality in patients with cirrhosis and low MELD-Na scores, and promote equitable allocation of donor livers. Lay abstract To receive a liver transplant, patients with cirrhosis need to be listed on the US liver transplant waiting list based on a score called the model for end-stage liver disease-Na (MELD-Na) score that is expected to accurately rank the patients based on urgency for a liver transplant. However, MELD-Na score is not sufficiently accurate to identify many patients with cirrhosis with the highest urgency, and this results in longer waiting times on the liver transplant list, and therefore higher death rates. We identified several metabolomic biomarkers that can increase the accuracy of the MELD-Na score, and optimize the allocation of donor livers for transplantation of patients with cirrhosis.