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

Abstract

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.

Mortality after urinary tract infections in patients with advanced cirrhosis – Relevance of acute kidney injury and comorbidities

“…Urinary tract infections (UTI) account for approximately one-third (13-43%) of bacterial infections in decompensated cirrhosis according to numerous prospective studies (2)(3)(4)(5)(6)(7)(8)(9). The prevalence of bacteriuria in cirrhotic patients is between 15% and 20% (10)(11)(12)(13) and, therefore, twice as high as in non-cirrhotic patients (11).…”

Alterations in cytokine measurements in ascitic fluid of cirrhotic patients with and without spontaneous bacterial peritonitis

“…From our observation in 13 patients, except AF IL-6, also TNF-a levels were shown to increase after SBP [15]. TNF-a is a macrophage derived cytokine, produced in large amounts in response to endotoxin.…”

Protein array technology to investigate cytokine production by monocytes from patients with advanced alcoholic cirrhosis: An ex vivo pilot study

“…First, several studies have shown that circulating levels of endotoxin are increased in patients with decompensated cirrhosis and no overt bacterial infection. 8,26,27,[36][37][38][39] In addition, in patients 8,38,40,41 and animals 42,43 with advanced cirrhosis there is evidence that "aseptic endotoxemia" is a result of an abnormal intestinal translocation of Gramnegative bacteria. Second, we have previously shown that the expression of toll-like receptor 4 (TLR4, which recognizes LPS) is altered at the surface of cirrhotic monocytes 7 and that overactivated TLR4 signaling (including MAP kinases and NF-kappaB) occurs at baseline in these cells.…”