{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T01:19:14Z","timestamp":1776388754712,"version":"3.51.2"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Nucleotide\u2010binding oligomerization domain containing 2 (<jats:italic>NOD2<\/jats:italic>) risk variants lead to impaired mucosal barrier function, increased bacterial translocation (BT), and systemic inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To evaluate the association between the presence of <jats:italic>NOD2<\/jats:italic> risk variants, BT, inflammation, and hepatic encephalopathy (HE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>This prospective multicenter study included patients with cirrhosis and testing for <jats:italic>NOD2<\/jats:italic> risk variants (p.R702W, p.G908R, c.3020insC, N289S, and c.\u2010958T&gt;C). Patients were evaluated for covert (C) and overt (O) HE. Markers of systemic inflammation (leukocytes, CRP, IL\u20106, LBP) and immune activation (soluble CD14) as well as bacterial endotoxin (hTRL4 activation) were determined in serum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 172 patients (70% men; median age 60 [IQR 54\u201366] years; MELD 12 [IQR 9\u201316]; 72% ascites) were included, of whom 53 (31%) carried a <jats:italic>NOD2<\/jats:italic> risk variant. In this cohort, 11% presented with OHE and 27% and CHE. Presence and severity of HE and surrogates of inflammation, BT, and immune activation did not differ between patients with and without a <jats:italic>NOD2<\/jats:italic> risk variant, also not after adjustment for MELD. HE was associated with increased ammonia and systemic inflammation, as indicated by elevated CRP (w\/o HE: 7.2 [2.7\u201316.7]; with HE 12.6 [4.5\u201329.7] mg\/dL; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and elevated soluble CD14 (w\/o HE 2592 [2275\u20133033]; with HE 2755 [2410\u20133456] ng\/mL; <jats:italic>p<\/jats:italic>\u2009=\u20090.025).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The presence of <jats:italic>NOD2<\/jats:italic> risk variants in patients with cirrhosis is not associated with HE and has no marked impact on inflammation, BT, or immune activation. In contrast, the presence of HE was linked to ammonia, the acute phase response, and myeloid cell activation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15627","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T09:33:27Z","timestamp":1685439207000},"page":"1793-1802","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Influence of <scp><i>NOD2<\/i><\/scp> risk variants on hepatic encephalopathy and association with inflammation, bacterial translocation and immune activation"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9704-4741","authenticated-orcid":false,"given":"Cristina","family":"Ripoll","sequence":"first","affiliation":[{"name":"Internal Medicine IV Jena University Hospital, Friedrich Schiller University  Jena 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