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Elevated levels of the long pentraxin 3 in paracetamol-induced human acute liver injury

Craig, Darren G.a; Lee, Patriciac; Pryde, Elizabeth A.c; Walker, Simon W.b; Beckett, Geoffrey J.b; Hayes, Peter Clivec; Simpson, Kenneth Jamesc

European Journal of Gastroenterology & Hepatology:
doi: 10.1097/MEG.0b013e32835ac77a
Original Articles: Complicated Liver Disorders
Abstract

Objectives: Pentraxin 3 (PTX3) is a long pentraxin with diverse humoral innate immune functions. The aims of this study were to measure levels of PTX3 and C-reactive protein (CRP), a hepatocyte-derived short pentraxin, in patients after acute liver injury.

Methods: PTX3 and CRP levels were measured in a total of 60 patients [48 paracetamol overdose (POD), 12 non-POD]. PTX3 expression was assessed by immunohistochemical analysis in explanted liver tissue.

Results: Admission PTX3 levels were significantly higher in POD acute liver failure (ALF) patients compared with POD non-ALF patients (P=0.0005) and non-POD patients (P=0.004). PTX3 levels in POD patients who died or required orthotopic liver transplantation (OLT, n=14) were significantly higher compared with those in spontaneous survivors (n=34, P=0.0011). The area under the receiver operator characteristic for PTX3 for death/OLT in POD patients was 0.80 (95% confidence interval 0.67–0.93). PTX3 levels were significantly higher in those POD patients who developed the systemic inflammatory response syndrome (P=0.001). Conversely, admission CRP levels were significantly lower in POD compared with non-POD patients (P=0.011), with no significant differences between survivors and nonsurvivors. After emergency OLT, PTX3 levels fell markedly; in contrast, CRP levels rapidly increased. Immunohistochemical analysis showed PTX3 expression in sinusoidal lining cells of a normal liver, infiltrating inflammatory cells in patients with ALF, and in a membranous distribution on injured hepatocytes in POD patients.

Conclusion: Increased PTX3 levels are associated with adverse outcomes following POD, suggesting that the humoral innate immune system plays an underrecognized role in this condition.

Author Information

aScottish Liver Transplantation Unit

bDepartment of Clinical Biochemistry, Royal Infirmary of Edinburgh, Little France

cDivision of Clinical and Surgical Sciences, University of Edinburgh, UK

Correspondence to Kenneth James Simpson, Scottish Liver Transplantation Unit, Royal Infirmary of Edinburgh, Little France, Edinburgh EH16 4SA, UK Tel: +44 131 242 1717; fax: +44 131 242 1633; e-mail: k.simpson@ed.ac.uk

Received April 19, 2012

Accepted September 26, 2012

© 2013 Lippincott Williams & Wilkins, Inc.