NOD2 gene variants are a risk factor for culture-positive spontaneous bacterial peritonitis and monomicrobial bacterascites in cirrhosis

Authors

  • Tony Bruns,

    1. Department of Internal Medicine II, Division of Gastroenterology, Hepatology, and Infectious Diseases, Jena University Hospital, Jena, Germany
    2. The Integrated Research and Treatment Center for Sepsis Control and Care (CSCC), Jena, Germany
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  • Jack Peter,

    1. Department of Internal Medicine II, Division of Gastroenterology, Hepatology, and Infectious Diseases, Jena University Hospital, Jena, Germany
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  • Philipp A. Reuken,

    1. Department of Internal Medicine II, Division of Gastroenterology, Hepatology, and Infectious Diseases, Jena University Hospital, Jena, Germany
    2. The Integrated Research and Treatment Center for Sepsis Control and Care (CSCC), Jena, Germany
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  • Dominik H. Grabe,

    1. Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany
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  • Sonja R. Schuldes,

    1. Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany
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  • Julia Brenmoehl,

    1. Department of Internal Medicine II, Division of Gastroenterology, Hepatology, and Infectious Diseases, Jena University Hospital, Jena, Germany
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  • Jürgen Schölmerich,

    1. Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany
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  • Reiner Wiest,

    1. Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany
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    • *Contributed equally.

  • Andreas Stallmach

    1. Department of Internal Medicine II, Division of Gastroenterology, Hepatology, and Infectious Diseases, Jena University Hospital, Jena, Germany
    2. The Integrated Research and Treatment Center for Sepsis Control and Care (CSCC), Jena, Germany
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    • *Contributed equally.



Tony Bruns, NIHR Biomedical Research Unit and Centre for Liver Research, Institute of Biomedical Research, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Tel:+44 121 414 6846
Fax:+44 121 415 8701
e-mail: t.bruns@bham.ac.uk

Abstract

Background: Spontaneous bacterial peritonitis (SBP) is considered as result of bacterial translocation from the gastrointestinal lumen to the mesenteric lymph nodes and subsequent circulation. Variants of the NOD2 gene contribute to bacterial translocation and were associated with SBP in a recent study.

Methods: We determined common NOD2 variants by TaqMan polymerase chain reaction and analysed the ascitic fluid neutrophil count and bacterial culture results in 175 prospectively characterized hospitalized patients with decompensated cirrhosis who underwent diagnostic paracentesis in two German centres.

Results: Ten patients presented with culture-positive SBP, 19 with culture-negative SBP and six had bacterascites. Minor allele frequencies for R702W, G908R and 1007fs in subjects with sterile non-neutrocytic ascites were 3.2, 2.5 and 2.5% respectively. Patients with SBP [odds ratio (OR) 2.7; P=0.036], culture-positive SBP (OR 6.0; P=0.012) and bacterascites (OR 6.0; P=0.050) were more often carriers of NOD2 variants than patients with sterile non-neutrocytic ascites. The mutations 1007fs and G908R were associated with culture-positive SBP (P≤0.005) and R702W with bacterascites (P=0.014). There was no significant association of NOD2 variants with culture-negative SBP (OR 1.6; P=0.493). In logistic regression, previous SBP, a higher model for end-stage liver disease (MELD) score and the presence of a NOD2 variant were independent predictors of ascitic fluid infection. The median survival was insignificantly shorter in patients with NOD2 variants (268 vs. 339 days; P=0.386). In patients without hepatocellular carcinoma at study entry (N=148), NOD2 was a predictor of survival after adjustment for the MELD score and age (hazard ratio 1.89; P=0.045).

Conclusion: NOD2 variants increase the risk for culture-positive SBP and bacterascites in cirrhosis and may affect survival.

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