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Basic science
P52 Neutrophil dysfunction: a potential biomarker of poor prognosis in acute liver failure?
  1. N Taylor,
  2. A Nishtala,
  3. F Lin,
  4. R D Abeles,
  5. W Bernal,
  6. J Wendon,
  7. Y Ma,
  8. D Shawcross
  1. Institute of Liver Studies, King's College Hospital, UK

Abstract

Introduction In acute liver failure (ALF) an exaggerated systemic inflammatory response can result in neutrophil activation with subsequent tissue damage from release of proteolytic enzymes and reactive oxygen species, contributing to ongoing organ failure. Neutrophil function in ALF has not been previously interrogated.

Aim This ongoing longitudinal study aims to characterise neutrophil function in patients with ALF admitted to King's College Hospital.

Method Neutrophils were isolated from a cohort of age/sex matched patients with ALF (n=22), healthy volunteers (n=9) and septic controls (n=5). Serial samples were taken on admission and every 3–4 days following ITU admission until death/discharge. Phagocytosis was analysed by flow cytometry using FITC-labelled E coli and oxidative burst (OB) was determined by the percentage of CD16-Phycoerytherin labelled neutrophils producing reactive oxygen species at rest and after stimulation with opsonised E coli. Physiological variables, biochemistry, arterial ammonia and microbial culture results were collected prospectively.

Results Within the ALF cohort 14 patients fulfilled poor prognostic criteria, of whom 8 underwent successful liver transplantation (LT) and 6 died without LT, 8 survived with medical management. Aetiology of ALF was acetaminophen n=5; acute viral hepatitis n=4; seronegative liver failure n=10; drug/other n=3. APACHE II and SOFA scores on admission were higher in patients with ALF compared to septic controls 21 (17–25) vs 12 (9–15) (p=0.08) and 16 (15–17) vs 5 (1–6) (p=0.01) respectively. Impaired neutrophil phagocytosis (p<0.01) and increased spontaneous OB (p=0.05) was observed on admission in all patients with ALF compared to both control groups. Admission neutrophil phagocytic dysfunction was associated with higher CRP*, MELD*, INR* and SOFA scores* (*all p<0.05). Spontaneous OB deteriorates further on days 4–8 in poor prognostic groups compared to spontaneous survivors (p=0.038). This was accompanied by decline in OB in response to E coli which was also observed in septic controls (p=0.045). The defects in neutrophil function showed a trend towards improvement (phagocytosis, spontaneous and stimulated OB all p=ns) during the first 72 h following successful LT.

Conclusion In conclusion, in patients with ALF fulfilling “poor prognostic criteria” neutrophils demonstrate early impairment of phagocytosis, increased baseline OB but decreased OB in response to bacterial stimulation. These observed defects are likely to contribute to ongoing cellular/organ dysfunction and the increased susceptibility to nosocomial sepsis seen in ALF.

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