CXCL10 levels identify individuals with rapid fibrosis at 12 months post-transplant for hepatitis C virus and predict treatment response

Clin Transplant. 2014 May;28(5):569-78. doi: 10.1111/ctr.12354. Epub 2014 Apr 21.

Abstract

Backgrounds: 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.

Keywords: CXCL10; fibrosis; hepatic stellate cell; hepatitis C virus; liver transplantation.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Allografts
  • Antiviral Agents / therapeutic use
  • Biomarkers / blood*
  • Chemokine CXCL10 / blood*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Graft Survival
  • Hepacivirus / isolation & purification*
  • Hepatitis C / blood
  • Hepatitis C / surgery*
  • Humans
  • Liver Cirrhosis / diagnosis*
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / mortality
  • Liver Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Postoperative Complications / diagnosis*
  • Postoperative Complications / drug therapy
  • Postoperative Complications / etiology
  • Postoperative Complications / mortality
  • Prognosis
  • ROC Curve
  • Recurrence
  • Risk Factors
  • Survival Rate
  • Young Adult

Substances

  • Antiviral Agents
  • Biomarkers
  • CXCL10 protein, human
  • Chemokine CXCL10