Clinical

Liver gene expression signature predicts chronic hepatitis C response to therapy

Last Updated: 2008-04-08 17:08:50 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Chronic hepatitis C patients who respond to combination therapy with pegylated interferon and ribavirin show a different liver gene expression signature than nonresponders, according to a report in the April Gut.

Because of the side effects and treatment cost of combination therapy for chronic hepatitis C, the authors explain, identification of probable virological nonresponders with reliable markers before therapy is "mandatory."

Dr. Tarik Asselah from University of Paris VII, AP-HP Beaujon Hospital, Clichy, France and colleagues sought to identify a liver gene expression signature that could predict treatment outcome in patients with chronic hepatitis C before treatment.

From a set of 58 genes associated with liver gene expression dysregulation during chronic hepatitis C in humans, the researchers identified a 2-gene classifier (IFI27 and CXCL9) that gave the highest overall accuracy in distinguishing sustained viral responders (SVR) from nonresponders (NR).

Specifically, this 2-gene classifier correctly identified 23 of 26 SVR and 8 of 14 NR patients in the training set and 14 of 29 SVR and all 9 NR patients in the independent test set, the authors report.

Similarly, a 3-gene classifier (IFI27, CXCL9, and IFI-6-16) proved accurate in 80.0% of the training set and 72.4% of the independent test set.

"Our study demonstrated that NR and SVR patients have different gene expression profiles prior to treatment," the authors conclude.

"The genes included in the signature encode molecules secreted in the serum and provide a logical functional approach for the development of serum markers to predict response to treatment," they add.

Gut 2008;57:516-524.