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

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

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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.

© 2013 Lippincott Williams & Wilkins, Inc.

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