title: Elevated levels of the long pentraxin 3 in paracetamol-induced human acute liver injury.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Increased PTX3 levels are associated with adverse outcomes following POD, suggesting that the humoral innate immune system plays an underrecognized role in this condition.
authors.affiliation: Scottish Liver Transplantation Unit, Royal Infirmary of Edinburgh, Little France, Edinburgh, UK.
authors.forename: Darren G
authors.initials: DG
authors.lastname: Craig
authors.forename: Patricia
authors.initials: P
authors.lastname: Lee
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Pryde
authors.forename: Simon W
authors.initials: SW
authors.lastname: Walker
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Beckett
authors.forename: Peter Clive
authors.initials: PC
authors.lastname: Hayes
authors.forename: Kenneth James
authors.initials: KJ
authors.lastname: Simpson
mesh_terms: D000082:Acetaminophen / Q000506:poisoning*; D000328:Adult; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000506:poisoning*; D019540:Area Under Curve; D001424:Bacterial Infections / Q000097:blood / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology / Q000401:mortality / Q000601:surgery; D016009:Chi-Square Distribution; D062787:Drug Overdose; D005260:Female; D006801:Humans; D056724:Immunity, Humoral; D007113:Immunity, Innate; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017114:Liver Failure, Acute / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000601:surgery; D016031:Liver Transplantation; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D012189:Retrospective Studies; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D000099153:Pentraxins
chemical_list: D000082:Acetaminophen; D018712:Analgesics, Non-Narcotic; D015415:Biomarkers; D002097:C-Reactive Protein; D018836:Inflammation Mediators; D016753:Interleukin-10; D015850:Interleukin-6; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C508609:IL10 protein, human; C508600:IL6 protein, human