Hyaluronic acid and endothelial damage due to paracetamol-induced hepatotoxicity.
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.


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.
Williams
Anna M
AM
Institute of Liver Studies, Guy's, King's & St Thomas' School of Medicine, London.
Langley
Peter G
PG
Osei-Hwediah
Johnson
J
Wendon
Julia A
JA
Hughes
Robin D
RD
D000082:Acetaminophen / Q000009:adverse effects*; D000293:Adolescent; D000328:Adult; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood; D017114:Liver Failure, Acute / Q000139:chemically induced* / Q000401:mortality / Q000628:therapy; D016031:Liver Transplantation; D008131:London; D008297:Male; D008875:Middle Aged; D010343:Patient Admission; D013223:Statistics as Topic; D016019:Survival Analysis; D018180:Thrombomodulin / Q000097:blood / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D014462:Ultrafiltration; D014841:von Willebrand Factor / Q000187:drug effects / Q000378:metabolism
D018712:Analgesics, Non-Narcotic; D015415:Biomarkers; D016209:Interleukin-8; D018180:Thrombomodulin; D014841:von Willebrand Factor; D000082:Acetaminophen; D006820:Hyaluronic Acid