Angiopoietin-2 in acute liver failure
Critical Care Medicine,

Hadem J et al. – The data show that circulating Angiopoietin–2, which potentially originates from the injured liver, correlates with several features of multiple organ dysfunction syndrome and independently predicts outcome. Tie2 agonists may have potential as an endothelium–targeted therapy to ameliorate multiple organ dysfunction syndrome and improve outcome in acute liver failure.

Methods
  • Thirty-seven patients with acute liver failure and 20 healthy control subjects.
  • Angiopoietin-2 levels were measured in sera from 37 patients with acute liver failure on admission and from 20 healthy control subjects.
  • Median age of patients with acute liver failure was 34yrs, 29 were female, and 21 developed encephalopathy grade 3 or greater.

Results
  • Nine patients survived to day 28 without transplantation, five died without transplantation, and 23 received a transplant.
  • Median (interquartile range) Angiopoietin-2 serum concentrations steadily increased across the following groups: healthy control subjects (1.4 [0.9–1.7]ng/mL), patients with transplant-free recovery (10.0 [4.7–12.1]ng/mL), and patients who reached the composite end point of death or emergency liver transplantation (16.8 [11.3–39.5]ng/mL).
  • Angiopoietin-2 release correlated strongly with surrogate markers of organ dysfunction and disease severity measures (lactate, platelet count, Sequential Organ Failure Assessment score, and Simplified Acute Physiology Score III).
  • Angiopoietin-2 levels were higher in patients with acute kidney injury and patients on mechanical ventilation.
  • Furthermore, Angiopoietin-2 levels were closely associated with Bilirubin–Lactate–Etiology score but not with other liver-specific markers.
  • Unadjusted and adjusted Cox’s proportional hazards analyses identified Angiopoietin-2 as a predictor of the composite end point of death or transplantation.
  • Finally, immunohistological studies showed that Angiopoietin-2 protein was upregulated in acute liver failure explants compared with matched liver biopsies obtained at baseline.

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