Ascites Due to Different Hepatic Diseases Known to have Differing Rates of Spontaneous Bacterial Peritonitis Have Unique Cytokine and Growth Factor Levels and Patterns in Ascitic Fluid

Abstract

Purpose: Individuals with viral and alcohol-associated cirrhosis are known to have high rates of spontaneous bacterial peritonitis. In contrast, individuals with ascites due to liver disease as a result of heart failure or malignancy rarely develop spontaneous bacterial peritonitis (SBP). Hypothesis: Differing patterns and levels of ascitic fluid cyctokine and growth factors exist between those with a high risk and low risk of SBP. Methods: Fifty-seven consecutive patients with ascites requiring a large-volume paracentesis were studied. Their age, gender, and 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/INR determination. The ascitic fluid was cultured, and a complete cell count and albumin determination was obtained on the fluid. In addition, blood and ascitic fluid was assessed for the levels of IL-1A, IL-1B, IL-2, IL-4, IL-8, IL-10, MCP-1, TNFα, IFNγ, VEGF, and 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 values ± 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 four 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 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 TNFα 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 ascites. These differences may be important in determining the risk for bacterial peritonitis, and suggest that high levels of IL-8, IL-10, and MCP in ascites may contribute to the lower risk for SBP. Obviously, sequential studies to include patients who have or develop SBP are needed to more precisely identify the cytokine and growth factor levels in ascitic patients who are at risk for SBP.