title: Serum neopterin and soluble CD163 as markers of macrophage activation in paracetamol (acetaminophen)-induced human acute liver injury.
abstract: BACKGROUND
  Macrophage activation is implicated in the pathogenesis of the systemic inflammatory response syndrome (SIRS) following paracetamol (acetaminophen) overdose (POD). Neopterin is synthesised from macrophages and reflects the intensity of monocyte/macrophage activation. Soluble CD163 (sCD163) is a marker of alternatively activated M2 macrophages.
  
  
  OBJECTIVE
  To examine neopterin and sCD163 levels in a cohort of acute liver injury patients.
  
  
  METHODS
  Consecutive patients (n = 41, (18 (43.9%) male) with acute liver injury were enrolled. Neopterin and sCD163 levels were measured by ELISA.
  
  
  RESULTS
  A total of 24/33 (72.7%) POD patients developed hepatic encephalopathy (HE), and therefore acute liver failure. Both neopterin and sCD163 levels were significantly higher in PODs compared with chronic liver disease (neopterin P < 0.001, sCD163 P = 0.038) and healthy (both P < 0.001) controls. Admission neopterin levels were significantly higher in PODs: with HE (P = 0.001); with the SIRS (P = 0.005); who required renal replacement therapy (P = 0.003); who died or required liver transplantation (P = 0.006; AUROC 78.6% (95% CI 62.2-94.9%). Serum sCD163 levels were significantly higher in those PODs with the SIRS (P = 0.033) on admission, and were higher in those PODs who died or required OLT (P = 0.024). Both admission neopterin and sCD163 levels in PODs correlated with organ failure scores but not with serum ALT. There was no significant correlation between neopterin and sCD163 values.
  
  
  CONCLUSIONS
  Both serum neopterin and sCD163 levels are significantly elevated following paracetamol overdose, and reflect the degree of macrophage activation in this condition. Serum neopterin in particular may have value as an early proxy marker of macrophage activation following paracetamol overdose.
authors.affiliation: Gastroenterology Department, The James Cook University Hospital, Middlesbrough, UK.
authors.forename: D G
authors.initials: DG
authors.lastname: Craig
authors.forename: P
authors.initials: P
authors.lastname: Lee
authors.forename: E A
authors.initials: EA
authors.lastname: Pryde
authors.forename: P C
authors.initials: PC
authors.lastname: Hayes
authors.forename: K J
authors.initials: KJ
authors.lastname: Simpson
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000328:Adult; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects*; D015703:Antigens, CD / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000209:etiology / Q000276:immunology; D005260:Female; D006501:Hepatic Encephalopathy / Q000097:blood; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D017114:Liver Failure, Acute / Q000097:blood / Q000139:chemically induced / Q000276:immunology; D008262:Macrophage Activation; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood*; D011956:Receptors, Cell Surface / Q000097:blood*; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood; D000098902:CD163 Antigen
chemical_list: D018712:Analgesics, Non-Narcotic; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D011956:Receptors, Cell Surface; D016753:Interleukin-10; D000082:Acetaminophen; D019798:Neopterin