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

Abstract

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. 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. 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. 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.