Hyaluronic acid and endothelial damage due to paracetamol-induced hepatotoxicity

Liver Int. 2003 Apr;23(2):110-5. doi: 10.1034/j.1600-0676.2003.00808.x.

Abstract

Background: Damage to endothelial cells may be an important factor in the complications of acute liver failure, resulting in multi-organ failure. The aim of this study was to assess endothelial cell function in patients with severe hepatotoxicity due to paracetamol ingestion.

Patients and methods: Fifty-eight patients with paracetamol-induced hepatotoxicity were studied for up to 7 days. Serum hyaluronic acid (HA), as a marker of hepatic sinusoidal endothelial cell function, was determined using an enzyme-linked binding assay. Plasma von Willebrand Factor, thrombomodulin and interleukin-8 were also determined using ELISA.

Results: Serum HA on admission was significantly increased (median 6777 ng/ml, range 24-50 967 ng/ml) as compared to normal controls (n = 10, median 21 ng/ml, range 0-50 ng/ml; P < 0.001). In non-survivors (n = 21) HA levels peaked on day 2 after admission (P = 0.044), and then decreased. In the survivors (n = 37) the levels of HA did not increase further. Plasma von Willebrand Factor, plasma thrombomodulin and serum interleukin-8 were significantly increased in the patients as compared to the normal controls (P < 0.001). Serum interleukin-8 was significantly higher in non-survivors in the first 2 days.

Conclusions: Endothelial function is abnormal in paracetamol-induced hepatotoxicity. Damage to hepatic sinusoidal endothelial cells assessed by serum HA was greater in non-survivors than survivors.

Publication types

  • Comparative Study

MeSH terms

  • Acetaminophen / adverse effects*
  • Adolescent
  • Adult
  • Aged
  • Analgesics, Non-Narcotic / adverse effects*
  • Biomarkers / blood
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology*
  • Female
  • Humans
  • Hyaluronic Acid / blood*
  • Interleukin-8 / blood
  • Liver Failure, Acute / chemically induced*
  • Liver Failure, Acute / mortality
  • Liver Failure, Acute / therapy
  • Liver Transplantation
  • London
  • Male
  • Middle Aged
  • Patient Admission
  • Statistics as Topic
  • Survival Analysis
  • Thrombomodulin / blood
  • Thrombomodulin / drug effects
  • Time Factors
  • Treatment Outcome
  • Ultrafiltration
  • von Willebrand Factor / drug effects
  • von Willebrand Factor / metabolism

Substances

  • Analgesics, Non-Narcotic
  • Biomarkers
  • Interleukin-8
  • Thrombomodulin
  • von Willebrand Factor
  • Acetaminophen
  • Hyaluronic Acid