Session Title: Category 2b. CIRRHOSIS AND ITS COMPLICATIONS: b. CLINICAL ASPECTS
Presentation Date: Apr 15, 2010
EVALUATION OF THE FUNCTIONAL CCL2 PROMOTER POLYMORPHISM -2518A>G AS RISK FACTOR FOR SPONTANEOUS BACTERIAL PERITONITIS AND DEATH IN DECOMPENSATED LIVER CIRRHOSIS
F. Grünhage1*, B. Appenrodt2, M. Gentenmann2, L. Thyssen2, S. Schwartz2, T. Sauerbruch2, F. Lammert1
1Medical Department II, Saarland University Hospital, Homburg, 2Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany. *firstname.lastname@example.org
Background: Factors influencing the development of spontaneous bacterial peritonitis (SBP) are poorly understood. We have shown that mutations in the nucleotide-binding oligomerization domain containing-2 (NOD2) gene are associated with both SBP and death in patients with liver cirrhosis (Appenrodt B et al. Hepatology in press). Clinical and experimental data also suggest that peritoneal macrophages contribute to the control of SBP via the chemokine CCL2 (MCP-1). Recently it was proposed that a functional promoter variant in the CCL2 gene is associated with SBP in patients with alcoholic cirrhosis (Gäble E et al. Z Gastroenterol 2008;46A). We therefore aimed to replicate this finding in a larger cohort of patients with decompensated liver cirrhosis.
Patients and methods: We recruited 145 patients with liver cirrhosis and ascites and recorded the development of SBP and survival. SBP was defined as presence of PMN count >250 cells/mL or positive bacterial culture from ascitic fluid. All individuals were genotyped for the CCL2 promoter polymorphism -2518A>G using dye fluorescent labelled probes in a real-time PCR-based genotyping assay.
Results: The majority of our patients presented with ascites due to alcoholic liver cirrhosis (62%) or chronic viral hepatitis (17%), all other aetiologies were less common. As expected, the majority of patients presented with advanced liver disease, with 94% of the patients classifying for Child-Pugh scores B or C. In total, 50 patients (34.4%) died. The median follow-up time was 98 days (range 1 - 938). Employing PMN cell count larger than 250 cells/µL and/or bacterial growth in culture as diagnostic criteria, 48 patients (33%) and 20 patients (14%) were diagnosed with SBP, respectively. Allele frequencies of the -2518A>G variant did not differ between patients with and without SBP regardless of the definition. In addition, we did not detect an association with CCL2 genotypes. Finally, we could not detect differences in survival between carriers of the rare allele or specific genotypes. Overall, the CCL2 genotype distribution was consistent with Hardy-Weinberg-equilibrium.
Conclusion: In contrast to NOD2 variants, our study does not support the previously reported association of chemokine variants and SBP in patients with decompensated liver cirrhosis.