Procalcitonin,and cytokines document a dynamic inflammatory state in non-infected cirrhotic patients with ascites

AIM:To quantitate the simultaneous serum and ascitic fluid levels of procalcitonin and inflammatory markers in cirrhotics with and without ascites.METHODS:A total of 88 consecutive severe cirrhotic patients seen in a large city hospital liver clinic were studied and divided into two groups,those with and without ascites.Group 1 consisted of 41 cirrhotic patients with massive ascites,as demonstrated by necessity for therapeutic large-volume paracentesis.Group 2consisted of 47 cirrhotic patients without any clinically documented ascites to include either a recent abdominal computed tomography scan or ultrasound study.Serum and ascitic fluid levels of an array of inflammatory markers,including procalcitonin,were measured and compared to each other and a normal plasma panel(NPP).RESULTS:The values for inflammatory markers assayed in the serum of Groups 1 and 2,and ascitic fluid of the Group 1.The plasma levels of the inflammatory cytokines interleukin(IL)-2,IL-4,IL-6,IL-8,interferon gamma(IFNγ)and epidermal growth factor(EGF)were all significantly greater in the serum of Group 1as compared to that of the serum obtained from the Group 2 subjects(all P<0.05).There were significantly greater serum levels of IL-6,IL-8,IL-10,monocyte chemoattractant protein-1,tumor necrosis factor-α,vascular endothelial growth factor and EGF when comparing Group 2 to the NPP.There was no significant difference for IL-1A,IL-1B,IL-2,IL-4 and IFNγlevels between these two groups.Serum procalcitonin levels were increased in cirrhotics with ascites compared to cirrhotics without ascites,but serum levels were similar to ascites levels within the ascites group.Furthermore,many of these cytokines,but not procalcitonin,demonstrate an ascites-to-serum gradient.Serum procalcitonin does not demonstrate any significant difference segregated by liver etiology in the ascites group;but ascitic fluid procalcitonin is elevated significantly in car-diac cirrhosis/miscellaneous subgroup compared to the hepatitis C virus and alcoholic cirrhosis subgroups.CONCLUSION:Procalcitonin in the ascitic fluid,but not in the serum,differentiates between cirrhotic subgroup reflecting the dynamic interplay of ascites,bacterial translocation and the peri-peritoneal cytokine.

Disease dependent qualitative and quantitative differences in the inflammatory response to ascites occurring in cirrhotics

AIM:To assess differing patterns and levels of ascitic fluid cyctokine and growth factors exist between those with a high risk and low risk of spontaneous bacterial peritonitis(SBP). METHODS: A total of 57 consecutive patients with ascites requiring a large volume paracentesis were studied. Their age, gender, specific underlying disease conditions were recorded after a review of their clinical records. Each underwent a routine assessment prior to their paracentesis consisting of a complete blood count, complete metabolic profile and prothrombin time/international normalized ratio(INR) determination. The ascitic fluid was cultured and a complete cellcount and albumin determination was obtained on the fluid. In addition, blood and ascitic fluid was assessed for the levels of interleukin interleukin(IL)-1A, IL-1B, IL-2, IL-4, IL-8, IL-10, monocyte chemotactic protein(MCP)-1, tumor necrosis factor(TNF)-α, interferon(IFN)-γ, vascular endothelial growth factor(VEGF) and epidermal growth factor(EGF) utilizing the Randox Biochip platforms(Boston, MA). A serum-ascites gradient, for each cytokine and growth factor was calculated. The results are reported as mean ± SEM between disease groups with statistical analysis consisting of the student t-test(two tailed) with a P value of 0.05 defining significance. RESULTS: No clinically important demographic or biochemical differences between the 4 groups studied were evident. In contrast, marked difference in the cytokine and growth factors levels and pattern were evident between the 4 disease groups. Individuals with alcoholic cirrhosis had the highest levels of IL-1A, IL-1B, IL-4, IFNγ. Those with malignant disease had the highest levels of IL-2. Those with hepatitis C virus(HCV) associated cirrhosis had the highest value for IL-6, IL-8, IL-10, MCP-1 and VEGF. Those with cardiac disease had the highest level of TNF-α and EGF. The calculated serum- ascites gradients for the cardiac and malignant disease groups had a greater frequency of negative values signifying greater levels of IL-8, IL-10 and MCP-1 in ascites than did those with alcohol or HCV disease. CONCLUSION: These data document important differences in the cytokine and growth factor levels in plasma, ascitic fluid and the calculated plasma- ascites fluid gradients in cirrhotics requiring a large volume paracentesis. These differences may be important in determining the risk for bacterial peritonitis.