Influence of NOD2 risk variants on hepatic encephalopathy and association with inflammation, bacterial translocation and immune activation

摘要

Abstract Background Nucleotide‐binding oligomerization domain containing 2 (NOD2) risk variants lead to impaired mucosal barrier function, increased bacterial translocation (BT), and systemic inflammation. Aim To evaluate the association between the presence of NOD2 risk variants, BT, inflammation, and hepatic encephalopathy (HE). Patients and Methods This prospective multicenter study included patients with cirrhosis and testing for NOD2 risk variants (p.R702W, p.G908R, c.3020insC, N289S, and c.‐958T>C). Patients were evaluated for covert (C) and overt (O) HE. Markers of systemic inflammation (leukocytes, CRP, IL‐6, LBP) and immune activation (soluble CD14) as well as bacterial endotoxin (hTRL4 activation) were determined in serum. Results Overall, 172 patients (70 men; median age 60 IQR 54–66 years; MELD 12 IQR 9–16; 72 ascites) were included, of whom 53 (31) carried a NOD2 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 NOD2 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 2.7–16.7; with HE 12.6 4.5–29.7 mg/dL; p?