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Ascitic fluid interleukin-8 to distinguish spontaneous bacterial peritonitis and sterile ascites in cirrhotic patients.

Spontaneous bacterial peritonitis (SBP) is a common and potentially fatal complication of cirrhosis. The pathogenesis of spontaneous ascitic fluid infection appears to involve translocation of bacteria from the gut to the mesenteric lymph nodes, depressed reticuloendothelial phagocytic activity, and deficient ascitic fluid antibacterial activity. A high index of suspicion of this infection and a low threshold for performing an abdominal paracentesis are required to detect infection early, when survival is most likely (1). Interleukin-8 (IL-8) is a cytokine produced by a variety of cells in response to stimuli, such as bacterial lipopolysaccharide, with a strong chemotactic activity on neutrophils. Increased plasma IL-8 has been observed in patients with severe infections as well as in alcoholic and nonalcoholic cirrhotic patients (2, 3). To our knowledge, IL-8 production in ascitic fluid in cirrhotic patients developing SBP has not been determined.

The aim of this study was to evaluate (a) IL-8 production in both plasma and ascitic fluid in cirrhotic patients with SBP and sterile ascites (SA); (b) the correlation of these values with neutrophil count in ascitic fluid; (c) the effect of therapy on IL-8; and (d) the sensitivity and specificity of ascitic fluid IL-8 in cirrhotic patients with ascites for detecting SBP patients.

Thirty-three cirrhotic patients were included in the study: 11 cirrhotic patients with SBP, and 22 patients with SA. A patient was classified as a SBP patient when the neutrophil count in the ascitic fluid was [greater than or equal to]250 cells/[micro]L and as a SA patient when neutrophil count in ascitic fluid was <250 cells/ [micro]L with negative ascitic fluid culture (1).

Patients with liver carcinoma or other neoplasms, with infections or recent antibacterial therapy (previous 2 weeks), and with gastrointestinal hemorrhage and under treatment with corticosteroids or pentoxifylline were excluded. Patients under prophylactic norfloxacin were not excluded. Patients classified as SBP-cirrhotic patients were treated with cefotaxime or a combination of amoxicillin-clavulanic acid.

To avoid interferences from cells, plasma and ascitic fluid samples were centrifuged immediately after collection. Blood samples were collected in EDTA tubes from a peripheral vein. Plasma was separated immediately by centrifugation (9008 for 15 min) and stored at -80 [degrees]C until assayed. Ascitic fluid samples were collected in EDTA tubes and stored at -80 [degrees]C until assayed.

Plasma and ascitic fluid IL-8 concentrations were determined by a solid-phase, two-site chemiluminescent enzyme immunometric assay (EURO/DPC) in an IMMULITE automated analyzer. Seven SBP patients had another IL-8 (plasma and ascitic fluid) determination at 48 h after onset of antibiotic treatment.

Statistically significant differences for IL-8 and other values in ascitic fluid and in plasma between groups were studied with the Mann-Whitney U-test. Regression analysis was carried out with the Spearman rank-order correlation. Wilcoxon analysis was used to evaluate the effects of therapy in SBP patients.

The distribution of patients by age, sex, cirrhosis etiology, prophylaxis, and alcohol consumption showed no significant differences between SBP patients and SA patients. Ascitic fluid IL-8 concentrations were greater in SBP patients than in the SA group (P <0.000001; Table 1). Ascitic fluid IL-8 showed a statistically significant correlation with ascitic fluid neutrophil count (r = 0.57; P <0.001). Wilcoxon analysis, which was used to evaluate the effects of therapy on IL-8 concentrations, showed a statistically significant decrease (P <0.05) in ascitic fluid IL-8 concentrations after 48 h of therapy. Ascitic fluid IL-8 concentrations on admission and at 48 h after the initiation of treatment are represented in Fig. 1.


A cutoff value of 100 ng/L for the ascitic fluid IL-8 concentration yielded 100% sensitivity and 100% specificity for diagnosis of spontaneous bacterial peritonitis in cirrhotic patients.

These data are the preliminary results of a larger study that is still ongoing to establish the possible prognostic value of ascitic fluid IL-8 in SBP patients. Two of 11 SBP patients developed septic shock, both patients having the highest ascitic fluid IL-8 concentrations. Up to now, we conclude that (a) IL-8 concentrations in ascitic fluid in SBP-cirrhotic patients are significantly greater than in patients with SA; (b) ascitic fluid IL-8 concentrations decrease from baseline to 48 h after the initiation of treatment in SBP patients; (c) in SBP patients, IL-8 concentrations in ascitic fluid are higher than plasma IL-8 concentrations, suggesting a local peritoneal production of IL-8 during SBP; (d) IL-8 seems to play a role in SBP in cirrhotic patients; and (e) IL-8 correctly classified SBP and SA patients.


(1.) Guarner C, Runyon BA. Spontaneous bacterial peritonitis: pathogenesis, diagnosis and management. Gastroenterologist 1995;3:311-28.

(2.) Huang Y-S, Chan C-Y, Wu J-C, Pai C-H, Chao Y, Lee S-D. Serum levels of interleukin-8 in alcoholic liver disease: relationship with disease stage, biochemical parameters and survival. J Hepatol 1996;24:377-84.

(3.) Sheron N, Bird G, Koskinas J, Portmann B, Ceska M, Lindley I, Williams R. Circulating and tissue levels of the neutrophil chemotaxin interleukin-8 are elevated in severe acute alcoholic hepatitis and tissue levels correlate with neutrophil infiltration. Hepatology 1993;18:41-5.

Cecilia Martinez-Bru, [1] * Cristina Gomez, [2] Mariano Cortes, [1] German Soriano, [2] Carlos Guarner, [2] Teresa Planella, [1] and Francesc Gonzalez-Sastre [1]

(Departments of [1] Biochemistry and [2] Gastroenterology, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain; * address correspondence to this author at: Servei de Bioquimica, Hospital de la Santa Creu i Sant Pau, Avgda. Pare Claret 167, 08025 Barcelona, Spain; fax 34-93-2919196, e-mail
Table 1. IL-8 and C-reactive protein in ascites
 fluid and plasma.

 SBP (n = 11), Sterile ascites (n = 22),
 median (quartiles) median (quartiles)
 min/max(a) min/max

AF IL-8,(b) ng/L 312(128-942) 36(32-46)
 106/41260 17/87
AF CRP,(c) mg/L 22.0 (9.2-27.7) 3.0 (0.1-6.8)
 0.1/90 0.1/18
AF neutrophils,(d) 1832(870-7670) 8(2-32)
 764/19674 0/210
Plasma IL-8,(e) ng/L 18(12-94) 14(7-71)
 5/631 5/283
Plasma CRP,(f) mg/L 35.7 (21.0-76.5) 15.4 (10.0-24.0)
 7.5/96.8 0.1/89.2

(a) min, minimum; max, maximum; AF, ascitic fluid; CRP,
 C-reactive protein.

(b) P <0.000001.

(c) P <0.0001.

(d) Neutrophil count was used to define SBP (>250 cells/[micro]L).

(e) Not significant at P = 0.05.

(f) P <0.005.
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Title Annotation:Technical Briefs
Author:Martinez-Bru, Cecilia; Gomez, Cristina; Cortes, Mariano; Soriano, German; Guarner, Carlos; Planella,
Publication:Clinical Chemistry
Date:Nov 1, 1999
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