ENDOTOXEMIA IN PATIENTS WITH CHRONIC LIVER-DISEASES - RELATIONSHIP TO SEVERITY OF LIVER-DISEASES, PRESENCE OF ESOPHAGEAL-VARICES, AND HYPERDYNAMIC CIRCULATION

Plasma endotoxin levels were investigated using a quantitative 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 cirrhosis, the plasma endotoxin levels progressively increased in relation to the severity of liver dysfunction (Pugh's 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 cirrhosis 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 cirrhosis 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 (8.0 +/- 0.5 vs. 6.6 +/- 0.4 1/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 hyperdynamic circulation found in patients with cirrhosis.