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

Darren G Craig, Patricia Lee, Elizabeth A Pryde, Simon W Walker, Geoffrey J Beckett, Peter Clive Hayes, Kenneth James Simpson

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)359-367
Number of pages9
JournalEuropean Journal of Gastroenterology & Hepatology
Volume25
Issue number3
DOIs
Publication statusPublished - Mar 2013

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