Background/Aims
The response rates of HCV infection to interferon therapy vary depending on viral
and host factors. We hypothesized that key regulators of the IFN signaling pathway
are predictive of treatment outcome.
Methods
We measured the expression of signal transducer and activator of transcription 1 (STAT1)
and suppressor of cytokine signaling 3 (SOCS3) in pretreatment liver biopsies. Staining
quantitation was compared to treatment outcomes.
Results
Forty-nine patients with HCV and 25 patients with HCV/HIV infection treated with peginterferon/ribavirin
were analyzed. Pretreatment hepatic SOCS3 expression was higher in non-responders
than responders. Genotype 1 responders had similar levels of SOCS3 as genotype 2/3
responders. African Americans (AA) had higher hepatic SOCS3 than non-AA. Pretreatment
hepatic SOCS3 was the most powerful independent predictor of sustained virologic response
(SVR), even more so than genotype by logistic regression analysis. Failure to achieve
SVR and AA race were independently associated with high hepatic SOCS3 levels. The
hepatic expression of STAT-1 did not differ between responders and non-responders.
Conclusions
Our data indicate that hepatic SOCS3 is a stronger baseline predictor of antiviral
response than viral genotype. Poor response to antiviral therapy in AA may be associated
with higher hepatic SOCS3 expression.
Abbreviations:
IFN (interferon), RBV (ribavirin), STAT1 (signal transducer and activator of transcription 1), SOCS3 (suppressor of cytokine signaling 3), HCV (hepatitis C virus), AA (African Americans), PEG-IFN (peginterferon)Keywords
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Article info
Publication history
Published online: February 17, 2009
Accepted:
December 9,
2008
Received in revised form:
November 11,
2008
Received:
May 29,
2008
Associate Editor: F. ZoulimFootnotes
☆Financial support: NIH AI069939, DK078772 (to R.T.C.) and Massachusetts Biomedical Research Corporation Tosteson Postdoctoral Fellowship (to A.W.T.). The authors declare that they do not have anything to disclose regarding funding from industries or conflict of interest with respect to this manuscript.
Identification
Copyright
© 2009 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
