Accuracy of circulating histones in predicting persistent organ failure and mortality in patients with acute pancreatitis

Background: Early prediction of acute pancreatitis severity remains a challenge. Circulating levels of histones are raised early in mouse models and correlate with disease severity. It was hypothesized that circulating histones predict persistent organ failure in patients with acute pancreatitis. Methods: Consecutive patients with acute pancreatitis fulfilling inclusion criteria admitted to Royal Liverpool University Hospital were enrolled prospectively between June 2010 and March 2014. Blood samples were obtained within 48 h of abdominal pain onset and relevant clinical data during the hospital stay were collected. Healthy volunteers were enrolled as controls. The primary endpoint was occurrence of persistent organ failure. The predictive values of circulating histones, clinical scores and other biomarkers were determined. Results: Among 236 patients with acute pancreatitis, there were 156 (66.1 per cent), 57 (24.2 per cent) and 23 (9.7 per cent) with mild, moderate and severe disease respectively, according to the revised Atlanta classification. Forty-seven healthy volunteers were included. The area under the receiver operating characteristic (ROC) curve (AUC) for circulating histones in predicting persistent organ failure and mortality was 0.92 (95 per cent c.i. 0.85 to 0.99) and 0.96 (0.92 to 1.00) respectively; histones were at least as accurate as clinical scores or biochemical markers. For infected pancreatic necrosis and/or sepsis, the AUC was 0.78 (0.62 to 0.94). Histones did not predict or correlate with local pancreatic complications, but correlated negatively with leucocyte cell viability (r = -0.511, P = 0.001). Conclusion: Quantitative assessment of circulating histones in plasma within 48 h of abdominal pain onset can predict persistent organ failure and mortality in patients with acute pancreatitis. Early death of immune cells may contribute to raised circulating histone levels in acute pancreatitis.