Gene signature aids outcome prediction in liver disease

Last Updated: 2015-08-07

By David Douglas

NEW YORK (Reuters Health) - Expression of hepatic stellate cell signature genes in hepatitis C cirrhosis and hepatocellular carcinoma (HCC) may help improve outcome prediction in patients following curative resection, according to new research.

"This study identifies a gene signature within liver derived from hepatic stellate cells that predicts clinical outcomes better than standard measures in patients with advanced liver disease," Dr. Scott L. Friedman of the Icahn School of Medicine at Mount Sinai, New York, told Reuters Health by email.

To derive this signature, Dr. Friedman and his colleagues compared stellate, immune and hepatic transcriptome profiles, they explain in a report online July 20 in Gut.

The team went on to test a 122-gene hepatic stellate cell signature consisting of genes encoding extracellular matrix proteins and developmental factors. This correlated with the extent of fibrosis in human, mouse and rat datasets.

They also developed a prognostic index combining bilirubin, platelet count and hepatic stellate cell signature expression using data from 216 patients with hepatitis C cirrhosis, 30% of whom developed HCC.

This was validated in 82 patients. Using cut-off values from the derivation set, 12% were deemed high risk and had significantly shorter overall survival (hazard ratio, 3.9), but not greater HCC recurrence. Addition of the gene signature set improved the model for prediction of both death and HCC recurrence.

"The prognostic index c-statistic for overall survival, the primary outcome, was 0.70 - this is the threshold generally regarded as clinically useful," the researchers say.

More development is needed, but Dr. Friedman concluded that the findings "provide a potential tool for more refined determination of clinical outcomes than is currently available, and also underscore the important contribution of hepatic stellate cells to liver function and risk of deterioration."

SOURCE: http://bit.ly/1eXvX7p

Gut 2015.