Driving Simulation and Cognitive Testing Can Improve Insight Into Impaired Driving Skills in Cirrhotic Patients With MHE

Abstract

Background/Aims: Episodes of bacterial translocation are associatedwith increased concentrations of endotoxin, which is able to prime and activate neutrophils and monocytes. Since variants of the nucleotide-binding oligomerization domain containing 2 (NOD2) gene impair the innate immune response and contribute to bacterial translocation, we hypothesized that the phagocyte resting burst is increased in patients with liver cirrhosis that carry NOD2 variants. Methods: The common NOD2 gene variants G908R, R702W, and 1007fs were determined in 35 non-infected patients with liver cirrhosis. The formation of reactive oxygen species in neutrophils and monocytes from these patients was monitored through the oxidation of dihydrorhodamine 123 to rhodamine by flow cytometry in whole blood and compared with that of 25 healthy controls. Results: The resting burst was increased in patients with liver cirrhosis compared to control subjects (P≤0.001). 8 of 35 cirrhotic patients were carriers of NOD2 variants. The spontaneous production of ROS in neutrophils (P=0.012) and monocytes (P=0.018) was increased in presence of a NOD2 mutation. A higher resting burst in neutrophils was also associated with a higher MELD score (r[s]= 0.388; P=0.023) and with Child-Pugh-Stage C (P=0.040). However, in a multivariate regression model only the presence of a NOD2 variant (P=0.019) and of ascites (P=0.016) were independent predictors of spontaneous ROS production in neutrophils (adjusted R2=0.231). Conclusion: The augmented neutrophil resting burst in patients with liver cirrhosis is further increased in presence of a NOD2 mutation which is suggestive of an increased bacterial translocation in these patients.