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.
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.
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.
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)
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Published online: February 17, 2009
Accepted: December 9, 2008
Received in revised form: November 11, 2008
Received: May 29, 2008Associate Editor: F. Zoulim
☆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.
© 2009 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.