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

J Hepatol. 2009 Apr;50(4):705-11. doi: 10.1016/j.jhep.2008.12.021. Epub 2009 Feb 14.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Biopsy
  • Black People / genetics
  • Black or African American
  • Female
  • Genotype
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • Hepacivirus / drug effects
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / pathology
  • Humans
  • Liver / physiopathology*
  • Male
  • Predictive Value of Tests
  • Racial Groups / genetics
  • STAT1 Transcription Factor / genetics*
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics*
  • Treatment Failure
  • Treatment Outcome
  • Viral Load
  • White People / genetics

Substances

  • Antiviral Agents
  • SOCS3 protein, human
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins