title: Intrahepatic mRNA levels of SOCS1 and SOCS3 are associated with cirrhosis but do not predict virological response to therapy in chronic hepatitis C.
abstract: BACKGROUND
  Antiviral treatment of chronic hepatitis C is not invariably successful, costly and associated with serious side-effects, and therefore should be indicated only when the chances of benefitting patients exceed the potential risks. The suppressor of cytokine signalling (SOCS) family members have been suggested to affect the rate of virological response to therapy, but the published evidence is conflicting.
  
  
  METHODS
  We measured the intrahepatic SOCS1, SOCS3 and SOCS7 mRNA levels in 107 chronic hepatitis C patients and assessed their clinical and histological correlates with the virological response to therapy and with some factors known for affecting treatment outcome.
  
  
  RESULTS
  By multivariate analysis, SOCS1, SOCS3 and SOCS7 mRNA levels were not associated with rapid or sustained virological response. Similarly, no association was found between the levels of any intrahepatic SOCS mRNA and those of the homeostasis model assessment of insulin resistance. Conversely, SOCS1 (OR 2.185, 95% CI 1.223-3.906, P=0.0083) and SOCS3 (OR 40.601, 95% CI 2.357-699.25, P=0.0108) mRNA level (but not SOCS7), together with age (OR 1.156, 95% CI 1.049-1.275, P=0.0036), were independently associated with cirrhosis.
  
  
  CONCLUSIONS
  Intrahepatic SOCS1, SOCS3 and SOCS7 mRNA levels do not predict virological response to therapy in chronic hepatitis C. The association between SOCS1, SOCS3 and cirrhosis warrants further study.
authors.affiliation: Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Pascarella
authors.forename: Sophie
authors.initials: S
authors.lastname: Clément
authors.forename: Michael T
authors.initials: MT
authors.lastname: Dill
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Conzelmann
authors.forename: Martin
authors.initials: M
authors.lastname: Lagging
authors.forename: Gabriele
authors.initials: G
authors.lastname: Missale
authors.forename: Avidan U
authors.initials: AU
authors.lastname: Neumann
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Laura
authors.initials: L
authors.lastname: Rubbia-Brandt
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Bochud
authors.forename: Francesco
authors.initials: F
authors.lastname: Negro
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D016014:Linear Models; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000821:virology; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000235:genetics* / Q000821:virology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009687:Nuclear Proteins / Q000235:genetics; D016017:Odds Ratio; D012333:RNA, Messenger / Q000032:analysis*; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000032:analysis / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009687:Nuclear Proteins; D012333:RNA, Messenger; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; C108775:SOCS7 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D012254:Ribavirin