As reported
in the April 2008 issue of Gut, French researchers attempted to identify
a liver gene signature that could predict sustained virological response (SVR;
continued undetectable HCV RNA 6 months after completion of treatment)
in chronic hepatitis C patients.
Based on prior literature, the investigators
selected 58 genes associated with liver gene expression dysregulation in the setting
of chronic hepatitis C. They used real-time quantitative RT-PCR to analyze the
messenger RNA (mRNA) expression of these genes in liver
biopsy specimens taken from patients before treatment.
First, they
looked for the suspect genes in a "training set" of 40 patients with
chronic hepatitis C, including 14 non-responders and 26 sustained responders (Group
A). They then determined whether these genes remained predictive in a "validation
set" of 29 patients, including 9 non-responders, 20 sustained responders,
and 11 individuals who initially responded but then relapsed after completing
therapy (Group B).
Results
•
Using data from Group A, the researchers identified 3 genes whose expression was
significantly increased in non-responders compared with sustained responders:
•
IFI-6-16/G1P3; •
IFI27; •
ISG15/G1P2.
•
These 3 genes also showed significant differences in their expression profiles
between non-responders and responders in the Group B.
•
Supervised class prediction analysis identified a two-gene signature (IFI27 and
CXCL9) that accurately predicted treatment response in 23 out of 29 patients (79%)
in Group B.
•
Predictive accuracy was 100% for non-responders and 70% for sustained responders.
•
Expression profiles of relapsers were not distinct, however, and 8 of the 11 (73%)
were incorrectly predicted to be responders based on the two-gene signature.
Conclusion
"Non-responders
and responders have different liver gene expression profiles before treatment,"
the study authors concluded.
"The most notable changes mainly occurred
in the interferon-stimulated genes," they added. "Treatment response
could be predicted with a two-gene signature (IFI27 and CXCL9)."
4/15/08
Reference T
Asselah, I Bieche. S Narguet, and others. Liver Gene Expression Signature to Predict
Response to Pegylated interferon plus Ribavirin combination therapy in Patients
with Chronic Hepatitis C. Gut 57(40: 516-524. April 2008.
