Z Gastroenterol 2011; 49 - P398
DOI: 10.1055/s-0031-1285669

Relevance of nucleotide-binding oligomerization domain containing 2 (NOD2) variants for the development of hepatic encephalopathy

L Mayer 1, M Krawczyk 1, F Grünhage 1, F Lammert 1
  • 1Saarland University Hospital, Department of Medicine II, Homburg, Germany

Background and aims: Hepatic encephalopathy (HE) is one of the major complications of liver cirrhosis, and spontaneous bacterial peritonitis (SBP) represents one of the most common triggers of HE. Our previous study identified three common NOD2 polymorphisms as genetic risk factors for SPB and increased mortality in cirrhotic patients (Hepatology 2010;51:1327–33). Now we aim to assess whether these three NOD2 variants also increase the risk of developing HE and/or aggravate HE severity in patients suffering from liver cirrhosis.

Patients and methods: In total 125 patients (80 males, 45 females; mean age 57.9 years, range 23–86) with liver cirrhosis mainly due to alcohol liver disease (58%) or chronic viral hepatitis (23%) were included. The mean MELD score at the time of admission was 13 (range 6–28); 42% of the patients presented with Child-Pugh scores B or C. HE was quantified by determination of critical flicker frequency (CFF). Individuals with CFF <38Hz (N=54) were classified to have HE. The NOD2 variants p.R702W, p.G908R and c.3020insC were genotyped by PCR-based assays with 5'-nuclease and fluorescence detection.

Results: The mean CFF value was 39.2Hz (range 28–58). NOD2 genotype distributions did not deviate from the Hardy-Weinberg equilibrium (all P>0.05). The p.R702W, c.3020insC and p.G908R risk alleles were carried by 13 (10.4%), 9 (7.2%) and 3 (2.4%) individuals, respectively. In total, 25 patients (20.0%) carried at least one NOD2 risk allele. The c.3020insC frequency was higher among cases as compared to controls (9.3 vs. 5.6%, respectively), however none of the studied polymorphisms separately nor carriership of at least one risk allele was associated with lower CFF values (all P>0.05). Accordingly, neither regression analysis nor restriction of cases cohort to individuals with severe HE (CFF <36Hz) provided evidence for an association between the NOD2 variants and HE.

Conclusion: Although common NOD2 polymorphisms substantially increase the risk of developing SBP, they do not confer an overt risk for HE in patients with liver cirrhosis.