Sequential changes in plasma cytokine and endotoxin levels in cirrhotic patients with bacterial infection

To delineate the clinical roles of plasma cytokine or endotoxin levels in the natural course of infection in patients with decompensated cirrhosis, 66 cirrhotic patients were studied within a 1.5-year period. Plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-8 and endotoxin were determined on days 1, 4 and 7 after admission when hospital infection was suspected and 4 months later. A total of 24 patients (36.4%) were proven to be infected during hospitalization (group A), while 42 others were not infected (group B). Fever occurred in a very high proportion (22/24) of group A patients. Baseline levels of TNF-alpha (37.7+/-15.2 compared with 8.7+/-1.2 pg/ml; P<0.01) and IL-6 (180.5+/-20.5 compared with 24.6+/-7.5 pg/ml; P<0.0001) were higher in group A patients, while IL-1beta, IL-8 and endotoxin levels were not significantly different between the two groups. For patients with hospital infection, IL-6 levels determined during the episode were significantly higher than baseline levels. Using IL-6 >80 pg/ml as a baseline cut-off level to diagnose bacterial infection, the sensitivity, specificity and accuracy were 87.5, 100 and 95.5% respectively. The one-year cumulative probability of mortality (61.1% compared with 23.7%; P<0.001) and of bacterial re-infection (72.2% compared with 18.4%; P<0.0001) was higher in group A than in group B. Plasma TNF-alpha and IL-6 levels determined at 4 months were not different between the two groups. In conclusion, fever or elevated plasma IL-6 levels in patients with decompensated cirrhosis calls for early antibiotic treatment to prevent life-threatening bacterial infection. Bacterial infection is likely to recur in those patients with increased IL-6 levels, while severe episodes of infection occur in patients with increased TNF-alpha levels.