Plasma endotoxin and tumor necrosis factor-alpha in the hyperkinetic state of cirrhosis.

OBJECTIVE

The factors which trigger the hyperdynamic circulation in cirrhosis remain poorly defined. Plasma levels of the potent vasodilators endotoxin and tumor necrosis factor-alpha may be elevated in patients with cirrhosis, and therefore the potential role of these substance was assessed in the hyperkinetic circulation in cirrhosis.

METHODS

Forty-nine patients in stable condition underwent systemic and hepatic hemodynamic measurements, and right atrial blood sampling for endotoxin and tumor necrosis factor-alpha assays. Patients were divided into three groups according to the severity of the disease: group 1 consisted of eight patients with normal liver or mild hepatic fibrosis, and groups 2 and 3 contained 17 and 24 patients with Child A and Child B or C cirrhosis, respectively.

RESULTS

Systemic vascular resistance decreased and cardiac index increased from group 1 to 3: 1530 +/- 196 dyn.s.cm-5 to 990 +/- 72 dyn.s.cm-5 (mean +/- S.E.; p<0.05) and 3.1 +/- 0.3 l.min-1.m-2 to 4.2 +/- 0.2 l.min-2.m-2, respectively. Endotoxin was not detectable in any of the groups and tumor necrosis factor-alpha was increased in one patient from group 1, six from group 2 and six from group 3. Mean tumor necrosis factor-alpha levels were not different among the groups (10 +/- 5, 18 +/- 5 and 17 +/- 7 pg/ml in groups 1, 2 and 3, respectively). Systemic vascular resistance and cardiac index were not correlated to plasma tumor necrosis factor-alpha levels; patients with increased levels of this cytokine did not have worse hyperdynamic circulation in any of the groups.

CONCLUSIONS

These results suggest that tumor necrosis factor-alpha and endotoxin do not play a role in the maintenance of the hyperkinetic state of cirrhosis.