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Acute deterioration of liver cirrhosis (e.g., infections, acute‐on‐chronic liver failure [ACLF]) requires an increase in cardiac contractility. The insufficiency to respond to these situations could be deleterious. Left ventricular global longitudinal strain (LV‐GLS) has been shown to reflect left cardiac contractility in cirrhosis better than other parameters and might bear prognostic value. Therefore, this retrospective study investigated the role of LV‐GLS in the outcome after transjugular intrahepatic portosystemic shunt (TIPS) and the development of ACLF. We included 114 patients (48 female patients) from the Noninvasive Evaluation Program for TIPS and Their Follow‐Up Network (NEPTUN) cohort. This number provided sufficient quality and structured follow‐up with the possibility of calculating major scores (Child, Model for End‐Stage Liver Disease [MELD], Chronic Liver Failure Consortium acute decompensation [CLIF‐C AD] scores) and recording of the events (development of decompensation episode and ACLF). We analyzed the association of LV‐GLS with overall mortality and development of ACLF in patients with TIPS. LV‐GLS was independently associated with overall mortality (hazard ratio [HR], 1.123; 95% confidence interval [CI],1.010‐1.250) together with aspartate aminotransferase (HR, 1.009; 95% CI, 1.004‐1.014) and CLIF‐C AD score (HR, 1.080; 95% CI, 1.018‐1.137). Area under the receiver operating characteristic curve (AUROC) analysis for LV‐GLS for overall survival showed higher area under the curve (AUC) than MELD and CLIF‐C AD scores (AUC, 0.688 versus 0.646 and 0.573, respectively). The best AUROC‐determined LV‐GLS cutoff was −16.6% to identify patients with a significantly worse outcome after TIPS at 3 months, 6 months, and overall. LV‐GLS was independently associated with development of ACLF (HR, 1.613; 95% CI, 1.025‐2.540) together with a MELD score above 15 (HR, 2.222; 95% CI, 1.400‐3.528). Conclusion: LV‐GLS is useful for identifying patients at risk of developing ACLF and a worse outcome after TIPS. Although validation is required, this tool might help to stratify risk in patients receiving TIPS.
Aim: NADPH oxidases are important sources of reactive oxygen species (ROS). Several Nox homologues are present together in the vascular system but whether they exhibit crosstalk at the activity level is unknown. To address this, vessel function of knockout mice for the cytosolic Nox organizer proteins p47phox, NoxO1 and a p47phox-NoxO1-double knockout were studied under normal condition and during streptozotocin-induced diabetes.
Results: In the mouse aorta, mRNA expression for NoxO1 was predominant in smooth muscle and endothelial cells, whereas p47phox was markedly expressed in adventitial cells comprising leukocytes and tissue resident macrophages. Knockout of either NoxO1 or p47phox resulted in lower basal blood pressure. Deletion of any of the two subunits also prevented diabetes-induced vascular dysfunction. mRNA expression analysis by MACE (Massive Analysis of cDNA ends) identified substantial gene expression differences between the mouse lines and in response to diabetes. Deletion of p47phox induced inflammatory activation with increased markers of myeloid cells and cytokine and chemokine induction. In contrast, deletion of NoxO1 resulted in an attenuated interferon gamma signature and reduced expression of genes related to antigen presentation. This aspect was also reflected by a reduced number of circulating lymphocytes in NoxO1-/- mice.
Innovation and conclusion: ROS production stimulated by NoxO1 and p47phox limit endothelium-dependent relaxation and maintain blood pressure in mice. However, NoxO1 and p47phox cannot substitute each other despite their similar effect on vascular function. Deletion of NoxO1 induced an anti-inflammatory phenotype, whereas p47phox deletion rather elicited a hyper-inflammatory response.