Endotoxemia in patients with chronic liver diseases: relationship to severity of liver diseases, presence of esophaegeal varices, and hyperdynamic circulation.

Plasma endotoxin levels were investigated using a quantitaive Limulus assay in patients with chronic liver diseases and correlated with the severity of liver diseases, the presence of esophageal varices, and hemodynamic parameters. The plasma endotoxin levels were significantly higher in chronic hepatitis patients with acute exacerbation (10.1±1.3 pg/ml. n=13, p<0.05) and patients with cirrhosis (7.0±0.7 pg/ml, n=126, p<0.05) than in healthy subjects (2.9±0.2 pg/ml, n=45). Chronic hepatitis patients (n=30) had plasma endotoxin levels which were similar to those in healthy subjects (4.6±0.5 vs. 2.9±0.2 pg/ml, p>0.05) but lower than those in chronic hepatitis patients with acute exacerbation (4.6±0.5 vs. 10.1±1.3 pg/ml, p<0.05). Endotoxemia (plasma endotoxin level>5.7 pg/ml) was found in 27%, 85% and 41% of patients with chronic hepatitis, chronic hepatitis with acute exacerbation, and cirrhosis, respectively. In patients with cirrhois, the plasma endotoxin leels progressively increased in relation to the severity of liver dysfunction (Pughʹs class A/B/C=4.9±0.5/7.9±1.4/10.2±2.0 (pg/ml, p<0.05). In contrast, plasma endotoxin levels were comparable between patients with cirrhois with and without esophageal varices (p>0.05). Chronic hepatitis patients with acute exacerbation (no collaterization) had much higher plasma endotoxin levels than those in patients with cirrhois and large varices (p<0.05), whereas compensated patients with cirrhosis and large esophageal varices had plasma endotoxin levels similar to those seen in chronic hepatitis patients (no collaterization) (p>0.05). A lower systemic vascular resistance (917±64 vs. 1167±69 dyn•s•cm−5, p<0.05) and a higher cardiac output (8.05±0.5 vs. 6.6 ±0.4 l/min, p<0.05) were found in patients with than without endotoxemia. No significant differences were observed in the hepatic venous pressure gradient between patients with cirrhosis with and without endotoxemia. These results demonstrate that endotoxemia is common in patients with chronic liver diseases. The severity of the liver disease is a more important factor than the presence of the esophageal varices for the development of endotoxemia. Endotoxemia may be responsible, at least in part, for the hydperdynamic circulation found in patients with cirrhois