Article Text

PDF
PP-010 Serum hepcidin: a predictor of early graft dysfunction following orthotopic liver transplantation?
  1. R Desai1,
  2. D Ward2,
  3. M Brookes2,
  4. C Tselepis2,
  5. A Holt1,
  6. T Iqbal2
  1. 1Department of Hepatology and Liver Transplantation, Queen Elizabeth Hospital, Birmingham, UK
  2. 2Department of Cancer studies, University of Birmingham, Birmingham, UK

Abstract

Introduction The hepatic peptide hepcidin is a critical regulator of iron metabolism. Serum levels of hepcidin correlate with liver function in humans and rodent studies have shown that liver injury modulate hepcidin expression. This is the first study of hepcidin levels in patients undergoing liver transplantation. We show that post-transplant serum hepcidin levels identify patients with severe preservation/reperfusion injury and hence predict graft dysfunction following liver transplantation.

Methods Serial serum hepcidin levels were measured by SELDI-TOF mass spectrometry in 11 patients undergoing liver transplantation. Liver biopsies (T0) were taken during transplantation in 9/11 patients. Clinicopathological, biochemical and haematological data were compared.

Results 5/11 patients had poor graft function after transplantation (determined by graft cholestasis, elevated PT and AST levels). Patients with poor graft function were more likely to have evidence of moderate/severe preservation injury at T0 biopsy than patients with normal graft function and were more likely to have received a liver from a non-heart beating (NHB) than a heart-beating donor (3/5 vs 1/7, respectively). While there was no difference in hepcidin levels between the two groups at the time of transplantation (90 vs 76 ng/ml p=0.68), the five patients with poor graft function had significantly higher hepcidin levels on day 3 post-transplantation compared to the six patients with mild preservation injury (Mean 135 (91–179) vs 39 (17–61) ng/ml, respectively, p< 0.01 ANOVA). Mean serum hepcidin values rose by 393% between day 1 and day 3 post transplant in the group with poor graft function whereas there was a 49% drop in serum hepcidin level in the group with normal function. The rise in hepcidin values at day 3 anticipated the onset of graft cholestasis in all of the patients with severe preservation injury.

Conclusion This is the first study of serum hepcidin levels in patients undergoing liver transplantation. We show that hepcidin values rapidly fall in patients with normal graft function following transplantation, but remain elevated in patients with early graft dysfunction. Elevated serum hepcidin levels accurately predicted the onset of preservation injury and anticipated graft dysfunction. Moreover we show that hepcidin levels are a better determinant of future graft dysfunction than AST or CRP. Early identification of graft dysfunction is important as it allows for modification of immunosuppression. We show that day 3 hepcidin levels correlate well with the severity of graft injury and can be used as a predictor of early graft dysfunction.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.