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

The factors which trigger the hyperdynamic circulation in cirrhosis remain poorly defined. Plasma levels of the potent vasodilators endotoxin and tumor necrosis factor-α may be elevated in patients with cirrhosis, and therefore the potential role of these substances 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-α 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 (mea±S.E.; p<0.05) and 3.1±0.3 l•min−1•min−2 to 4.2−0.2 l•min−1•m−2, respectively. Endotoxin was not detectable in any of the groups and tumor necrosis factor-α was increased in one patient from group 1, six from group 2 and six from group 3. Mean tumor necrosis factor-α 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-α 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-α and endotoxin do not play a role in the maintenance of the hyperkinetic state of cirrhosis