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Metabolic profiling predicts mortality in decompensated cirrhosis

Plasma metabolic profiling was accurate in predicting morality among patients with decompensated cirrhosis, according to recent study data.

“Metabolic profiling has been applied in inflammatory bowel disease, hepatocellular carcinoma and to a limited extent, liver failure … no studies have assessed how profiling could prognosticate and none uses a combination of technologies to develop a global overview of the metabolic signature of poor survival in [decompensated cirrhosis],” the researchers wrote.

The researchers included 80 patients with decompensated cirrhosis in a derivation cohort who underwent plasma metabotyping using 1H nuclear magnetic resonance (NMR) spectroscopy and reversed-phase ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC-TOF-MS), to determine whether high-resolution metabolic profiling can determine any metabolic phenotype associated with 90-day survival.

In addition to the derivation cohort, 20 patients with stable cirrhosis, 20 age- and sex-matched healthy controls, another validation cohort of 101 patients hospitalized for decompensated cirrhosis and 27 healthy controls were included for further analysis.

Sixty-two of the 80 patients spontaneously survived, according to the research. Patients who did not survive showed signs of higher MELD and Child-Pugh score vs. survivors. The 1H NMR metabotyping showed discrimination between surviving and non-surviving patients with decompensated cirrhosis. The NMR plasma profiles of non-survivors were attributed to reduced phosphatidylcholines and lipid resonances, with increased lactate, tyrosine, methionine and phenylalanine signal intensities. These attributions were also observed on external validation, which showed an area under the receiver operating curve (AUROC) of 0.96 (95% CI, 0.9–1), with a sensitivity of 98% and specificity of 89%.

Lysophosphatidylcholines (LPC) and phosphatidylcholines were lower in nonsurvivors, as seen by UPLC-TOF-MS (AUROC of 0.94; 95% CI, 0.89–0.98). LPC levels were negatively correlated with M30 and M65 circulating markers among patients with decompensated cirrhosis. Liver tissue examinations confirmed high hepatocyte cell death in patients with decompensated cirrhosis compared with controls. In addition, cross liver sampling pre-liver transplantation showed that hepatic endothelial beds increase circulating total cytokeratin-18 in decompensated cirrhosis.

The researchers concluded: “Plasma metabotyping accurately predicts mortality in [decompensated cirrhosis]. LPC and amino acid dysregulation is associated with increased mortality and severity of disease reflecting hepatocyte cell death.” – by Melinda Stevens

Disclosure: The researchers report no relevant financial disclosures.