title: CXCL10 levels identify individuals with rapid fibrosis at 12 months post-transplant for hepatitis C virus and predict treatment response.
abstract: BACKGROUND
  Recurrent hepatitis C virus (HCV) infection is universal post-transplantation. Fibrosis (F) stage ≥2 at 12 months identifies patients with rapid fibrosis progression. Antiviral therapy (AVT) remains the only option to attenuate fibrosis progression. We hypothesized that CXCL10 levels can distinguish between slow and fast fibrosis progression at 12 months, development of F ≥ 4 post-transplantation, and help predict treatment response in patients undergoing AVT.
  
  
  METHODS
  All patients that had undergone primary liver transplantation at King's College Hospital, London, between 2000 and 2011 were identified. Quantification of CXCL10 was performed using an ELISA-based assay on stored plasma at six months post-transplant and pre-treatment. Comparison was made with liver biopsies performed at 12 months and in the post-transplant period where available.
  
  
  RESULTS
  One hundred and thirty-three patients were included. CXCL10 levels were lower in the slow fibrosis group compared to the rapid fibrosis group (p < 0.0001). CXCL10 correlated with F stage, necro-inflammatory score, and serum transaminases (<0.0001). CXCL10 was an independent predictor of F ≥ 2 at 12 months and F ≥ 4 (p < 0.05). Pre-treatment CXCL10 levels were an independent predictor of sustained virologic response (p = 0.04).
  
  
  CONCLUSIONS
  CXCL10 levels help identify patients with rapid fibrosis progression in patients with recurrent HCV and those that are likely to respond to AVT.
authors.affiliation: Institute of Liver Studies, King's College Hospital, London, UK.
authors.forename: Deepak
authors.initials: D
authors.lastname: Joshi
authors.forename: Ivana
authors.initials: I
authors.lastname: Carey
authors.forename: Matthew
authors.initials: M
authors.lastname: Foxton
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Freah
authors.forename: Matthew
authors.initials: M
authors.lastname: Bruce
authors.forename: Nigel
authors.initials: N
authors.lastname: Heaton
authors.forename: Alberto
authors.initials: A
authors.lastname: Quaglia
authors.forename: John
authors.initials: J
authors.lastname: O'Grady
authors.forename: Varuna
authors.initials: V
authors.lastname: Aluvihare
authors.forename: Kosh
authors.initials: K
authors.lastname: Agarwal
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064591:Allografts; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D054357:Chemokine CXCL10 / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D016174:Hepacivirus / Q000302:isolation & purification*; D006526:Hepatitis C / Q000097:blood / Q000601:surgery*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology / Q000401:mortality; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology / Q000401:mortality; D011379:Prognosis; D012372:ROC Curve; D012008:Recurrence; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10
keywords: CXCL10; fibrosis; hepatic stellate cell; hepatitis C virus; liver transplantation