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Biological Chemistry

Cirrhosis Diagnosis

Biomarkers: Fingerprint of urinary metabolites reflects the stage of liver cirrhosis

by Kenneth J. Moore
May 30, 2012

A newly identified set of metabolites in people’s urine could help doctors detect and predict the outcome of cirrhosis of the liver (J. Proteome Res., DOI: 10.1021/pr300337s).

Chronic liver disease can lead to cirrhosis, a sometimes-fatal condition involving liver scarring and decreased liver function. Doctors diagnose three stages with increasing severity of disease; the stage dictates what treatment is most effective.

Currently, doctors rely on a battery of diagnostic tests, including blood tests for liver enzymes and detection of excess fluid in the abdomen. But these methods don’t provide direct evidence of the stage of a patient’s cirrhosis, so doctors must make a diagnosis using past clinical experience or an invasive liver biopsy.

Wei Jia of the University of North Carolina, Greensboro, and colleagues in China wanted to find a more direct, less invasive means of pinpointing the stage. Using gas chromatography/mass spectrometry and ultraperformance liquid chromatography/time-of-flight mass spectrometry, they analyzed metabolites in the urine of 63 men who developed the condition after having chronic hepatitis B infections. The researchers also measured the metabolites in the urine of 31 healthy males.

They found 39 metabolites, including estrone and α-hydroxyhippurate, whose urine concentrations differed significantly between the patients and healthy people. Based on the concentrations of these compounds, the researchers developed a statistical model that could predict if a patient had cirrhosis and if so, what stage the disease had reached.

Jia admits that the time and analytical equipment needed to measure the metabolite concentrations makes the method impractical for routine testing. But he hopes that others will build on it to design a more clinic-friendly diagnostic method.

“There is an urgent need for improved, noninvasive biomarkers of cirrhosis stages,” says Scott L. Friedman, a professor of liver diseases at Mount Sinai Hospital. He thinks that this metabolic fingerprint method shows promise as a diagnostic tool. The researchers should confirm its predictive power in patients whose cirrhosis had other causes, Friedman adds.

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