Hepatic SOCS3 expression is strongly associated with non-response to therapy and race in HCV and HCV/HIV infection

JOURNAL OF HEPATOLOGY

卷:50

Article

Kim, Kyung-Ah^1,2  Lin, Wenyu¹  Tai, Andrew W.¹  Shao, Run-Xuan¹  Weinberg, Ethan¹  De Sa Borges, Carolina B.¹  Bhan, Atul K.⁴  Zheng, Hui³  Kamegaya, Yoshitaka¹  Chung, Raymond T.¹ 

[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA

[2] Inje Univ, Ilsan Paik Hosp, Dept Med, Goyang, South Korea

[3] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Biostat,Dept Med, Boston, MA 02114 USA

[4] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

关键词: Suppressor of cytokine signaling 3;    Hepatitis C virus;    HCV/HIV coinfection;    Race;    Immunohistochemistry;    Signal transducer and activator of transcription 1;   

DOI  :  10.1016/j.jhep.2008.12.021

来源: Elsevier

【 摘 要 】

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 213 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. (c) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

【 授权许可】

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