32 (Table 4B). Overall, eight (5.3%) patients fulfilled the criteria of SIRS at time of admission. Of these, three patients had NOD2 risk variants, and five patients carried no NOD2 variants. During follow-up, nine patients died due to SIRS (Table 2; four patients

with and five patients without NOD2 variants). Table 5A demonstrates that patients carrying a risk allele of any of the three NOD2 variants developed SBP, defined as PMN cell count >250/μL, more frequently at index paracentesis or during follow-up (OR = 3.06, 95% confidence interval [CI] = 1.31–7.15, P = 0.008). In addition to these 30 patients (Table 5A), SBP was documented in 22 additional patients before inclusion in the study. Table 5B shows that the combined prospective and retrospective analysis of both groups together substantiated the association between NOD2 and SBP and indicated a similarly increased Maraviroc risk of SBP (OR = 2.98; Everolimus 95% CI = 1.39–6.40, P = 0.004). Although the risk allele frequencies of all NOD2 variants tended to be higher in patients with SBP (Table 3), no statistically significant differences were observed for individual NOD2 SNPs. In ascites samples from 15 patients (10%), we detected bactDNA, and four of these patients

carried NOD2 risk alleles. However, contingency table analysis did not support an association between NOD2 genotypes and the presence of bactDNA. In this study we report a significant association of SBP with common risk variants of the NOD2 selleck products gene in patients with

advanced liver cirrhosis and ascites. Importantly, the study demonstrates that the NOD2 variants confer a substantially increased risk for death in patients with cirrhosis. Increased bacterial translocation in cirrhosis has been attributed to structural changes of the intestinal mucosa including dilatation of intercellular space and vascular congestion as well as mucosal oxidative damage.4, 8, 21 Furthermore, innate and adaptive immune responses normally limit the penetration of bacteria across the epithelium, but activation and transmigration of PMN cells cause the release of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) as well as nitric oxide, all of which modulate bacterial translocation.4, 8, 9, 22 In the present study we identified NOD2 variants as novel inherited risk factors for SBP in liver cirrhosis. In our prospective analysis, the OR for SBP was about 3 (Table 5A), and this high ratio is in the range of other disease risks conferred by the NOD2 variants.10, 23 Although the results were corroborated by the combined prospective and retrospective analysis that took both occurrence of SPB during follow-up and previous history of SBP into account and resulted in a similar OR (Table 5B), our study warrants further evaluation and needs to be replicated in an independent population.