ENDOTOXEMIA IN PATIENTS WITH CHRONIC LIVER-DISEASES - RELATIONSHIP TOSEVERITY 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 h emodynamic 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 le vels 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 hepati tis 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, pla sma endotoxin levels were comparable between patients with cirrhosis w ith and without esophageal varices (p > 0.05). Chronic hepatitis patie nts with acute exacerbation (no collaterization) had much higher plasm a endotoxin levels than those in patients with cirrhosis and large var ices (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 endotoxem ia. No significant differences were observed in the hepatic venous pre ssure gradient between patients with cirrhosis with and without endoto xemia. These results demonstrate that endotoxemia is common in patient s 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 lea st in part, for the hyperdynamic circulation found in patients with ci rrhosis.