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

Eur J Gastroenterol Hepatol. 2013 Mar;25(3):359-67. doi: 10.1097/MEG.0b013e32835ac77a.

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.

Publication types

  • Comparative Study

MeSH terms

  • Acetaminophen / poisoning*
  • Adult
  • Aged
  • Analgesics, Non-Narcotic / poisoning*
  • Area Under Curve
  • Bacterial Infections / blood
  • Bacterial Infections / immunology
  • Biomarkers / blood
  • C-Reactive Protein / metabolism*
  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / diagnosis
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / immunology
  • Chemical and Drug Induced Liver Injury / mortality
  • Chemical and Drug Induced Liver Injury / surgery
  • Chi-Square Distribution
  • Drug Overdose
  • Female
  • Humans
  • Immunity, Humoral
  • Immunity, Innate
  • Immunohistochemistry
  • Inflammation Mediators / blood
  • Interleukin-10 / blood
  • Interleukin-6 / blood
  • Liver / drug effects*
  • Liver / immunology
  • Liver / metabolism
  • Liver / pathology
  • Liver Failure, Acute / blood
  • Liver Failure, Acute / chemically induced*
  • Liver Failure, Acute / diagnosis
  • Liver Failure, Acute / immunology
  • Liver Failure, Acute / mortality
  • Liver Failure, Acute / surgery
  • Liver Transplantation
  • Logistic Models
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • ROC Curve
  • Retrospective Studies
  • Serum Amyloid P-Component / metabolism*
  • Systemic Inflammatory Response Syndrome / blood
  • Systemic Inflammatory Response Syndrome / immunology
  • Time Factors
  • Treatment Outcome
  • Up-Regulation

Substances

  • Analgesics, Non-Narcotic
  • Biomarkers
  • IL10 protein, human
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-6
  • Serum Amyloid P-Component
  • Interleukin-10
  • PTX3 protein
  • Acetaminophen
  • C-Reactive Protein