Introduction The innate immune response may underpin the development of multiorgan failure following acute liver injury, particularly following paracetamol overdose (POD). Pentraxin 3 (PTX3) is a long pentraxin induced by interleukin (IL)-10, and produced by vascular endothelium, macrophages, and myeloid dendritic cells. PTX3 has diverse effector functions including opsonisation, clearance of apoptotic debris, and tissue repair.
Aim To measure levels of PTX3 and C-reactive protein (CRP), a hepatocyte derived short pentraxin involved in the acute phase response, in patients with acute liver injury.
Method Consecutive patients admitted to the Royal Infirmary of Edinburgh with acute liver injury (ALT>1000 IU/l and coagulopathy) were enrolled. PTX3 and CRP levels were measured by ELISA and turbimetry, respectively.
Results A total of 60 patients (48 POD, 12 non-POD) were enrolled. 28/48 (58.3%) of POD and 8/12 (66.7%) non-POD patients developed hepatic encephalopathy (HE), and therefore acute liver failure. As expected, admission PTX3 levels correlated strongly with IL-10 (Spearman's r=0.641, p<0.001), but also correlated with INR (r=0.728, p<0.001) and ALT (r=0.554, p<0.001), but not with CRP (r=-0.124, p=0.35). Admission PTX3 levels were significantly higher in POD patients with HE (median (interquartile range) 329.4 (77.7–738.1 ng/ml)) compared with POD patients without HE (46.1 (6.1–172.4) ng/ml, p=0.0005), or with non-POD patients (23.7 (9.1–40.0) ng/ml, p=0.004). PTX3 levels in POD patients who died or required emergency liver transplantation (LT) (772.9 (268.2–848.7) ng/ml) were significantly higher compared with spontaneous survivors (81.1 (12.0–437.1), p<0.0001), with an area under the receiver operator characteristic curve of 80.3 (95% CI 67.1 to 93.4). Admission PTX3 levels in POD patients correlated with admission APACHE II (r=0.398, p=0.006) and SOFA (r=0.536, p<0.001) scores, and were higher in POD patients who developed the systemic inflammatory response syndrome (SIRS 306.4 (113.9–764.7) ng/ml, no SIRS 50.5 (6.66–297.7) ng/ml, p=0.001). Conversely, admission CRP levels were significantly decreased in POD patients (6.05 (3.93–15.38) mg/l) compared with non-POD patients (17.6 (3.9–15.4) mg/l, p=0.011). There were no significant differences in CRP levels between POD patients who died/required LT (5.2 (4.3–15.9) mg/l) and survivors (7.9 (3.5–15.7) mg/l, p=0.820).
Conclusion These data suggest that the humoral arm of the innate immune system plays an important role in the pathogenesis of multiorgan failure following POD. PTX3 may have a role as a novel prognostic marker in this condition.
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