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News

Gene signature identifies cirrhosis risk in Hep C patients

This month's issue of Hepatology reports that a 7 gene signature identifies the risk of developing cirrhosis in patients with chronic Hep C.

News image

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Clinical factors such as age, gender, alcohol use, and age-at-infection influence the progression to cirrhosis but cannot accurately predict the risk of developing cirrhosis in patients with chronic Hepatitis C.

Dr Hongjin Huang and colleagues from California, USA developed a predictive signature for cirrhosis in Caucasian patients.

All patients had well-characterized liver histology and clinical factors.

The research team extracted DNA from whole blood for genotyping.

The researchers validated all significant markers from a genome scan in the training cohort, and selected 361 markers for the signature building.

Using a machine learning approach, a signature consisting of markers most predictive for cirrhosis risk in Caucasian patients was developed in the training set of 420 patients.

A high cutoff value would misclassify 22% of low-risk patients
Hepatology

The Cirrhosis Risk Score was calculated to estimate the risk of developing cirrhosis for each patient.

The team then tested the Cirrhosis Risk Score performance in an independently enrolled validation cohort of 154 Caucasian patients.

A Cirrhosis Risk Score signature consisting of 7 markers was developed for Caucasian patients.

The area-under-the-receiver of operator curve of the Cirrhosis Risk Score was 0.75 in the training cohort.

In the validation cohort, the team found that the area-under-the-receiver of operator curve was only 0.53 for clinical factors.

The area-under-the-receiver of operator curve increased to 0.73 for Cirrhosis Risk Score, and 0.76 when Cirrhosis Risk Score and clinical factors were combined.

A low Cirrhosis Risk Score cutoff of less 0.50 to identify low-risk patients would misclassify only 10% of high-risk patients.

The researchers observed that a high cutoff value over 0.70 to identify high-risk patients would misclassify 22% of low-risk patients.

Dr Huang's team comments, "Cirrhosis Risk Score is a better predictor than clinical factors in differentiating high-risk versus low-risk for cirrhosis in Caucasian chronic Hepatitis C patients."

"Prospective studies should be conducted to further validate these findings."

Hepatology 2007: 46: 2: 297-306
01 August 2007

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