Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment for complications of portal hypertension; yet the influence of anesthesia modality on procedural performance and hemodynamics remains insufficiently characterized. This retrospective single-center study compared radiation exposure, procedural parameters, and portal hemodynamics between procedures performed with and without general anesthesia (GA). A total of 84 patients were identified, of whom 62 were age- and sex-matched into two equal groups: group 1 (GA, n = 31) and group 2 (no GA, n = 31). Evaluated parameters included length of hospital stay, dose area product (DAP), fluoroscopy time (FT), contrast volume, number of digital subtraction angiography series, procedure duration, and pre- and post-TIPS measurements of portal venous pressure, central venous pressure (CVP), and portosystemic pressure gradient (PPG). Non-parametric statistical tests were applied. Patients in group 1 had significantly shorter postoperative hospital stay (median 6 days; interquartile range (IQR): 4-7) than those in group 2 (8 days; IQR 6-8; p = 0.006). Radiation dose was significantly lower in group 1, with a median DAP of 127.1 Gy*cm2 (IQR 64.6-201.8) compared to 325 Gy*cm2 (IQR 162.3-393.7; p = 0.02) in group 2. FT was also reduced under GA (12.2 minutes; IQR 9.6-15.9 vs. 16.0 minutes; IQR 11.5-25.9; p = 0.01), as was contrast volume (75 ml; IQR 60-100 vs. 90 mL; IQR 60-110; p = 0.01). PPG reduction was achieved in both groups, despite higher CVP under GA. These findings suggest that GA may facilitate more stable procedural conditions during TIPS, reducing radiation dose and contrast use without compromising hemodynamic effectiveness.

BACKGROUND AND AIMS:Patients with acutely decompensated cirrhosis (ADC) present severe immune dysfunction characterized by smoldering systemic inflammation and persistent immunosuppression, rendering them at increased risk of bacterial infections and acute-on-chronic liver failure (ACLF). APPROACH AND RESULTS:We explored the profile of 98 immunomodulatory lipid mediators in patients with ADC with and without ACLF and their effects on leukocyte function. We performed liquid chromatography coupled to tandem mass spectrometry-based lipidomics of 308 plasma samples longitudinally collected from 93 patients with ADC with and without ACLF and integrated expression and flow cytometry data with functional assays in leukocytes. Lipidomics identified the linoleic acid-derived leukotoxin 9,10-dihydroxy-12-octadecenoic acid (9,10-DiHOME) as the only lipid mediator elevated in ACLF. 9,10-DiHOME levels followed the disease severity course and peaked when patients acquired infections and developed ACLF. Leukocytes from patients with ADC showed increased expression of soluble epoxide hydrolase, the enzyme responsible for 9,10-DiHOME biosynthesis. In polymorphonuclear leukocytes, 9,10-DiHOME impaired degranulation, phagocytosis, and respiratory burst capacities. In mononuclear leukocytes, this lipid mediator induced the expression of the immunosuppressive marker MerTK, impaired their ability to produce cytokines in response to lipopolysaccharide and disrupted mitochondrial dynamics and autophagic responses. Inhibition of soluble epoxide hydrolase in vivo reduced immunosuppressive responses in peritoneal macrophages and significantly attenuated MerTK expression in liver macrophages. CONCLUSIONS:These findings indicate that increased levels of the leukotoxin 9,10-DiHOME weaken immune cell defensive responses and position soluble epoxide hydrolase as a potential drug target in ADC.

Dysfunction of the gut-liver axis is a key pathomechanism for progression of liver cirrhosis and the development of life-threatening complications. This review summarizes the current state of knowledge on the gut-liver axis and highlights its clinical relevance. Disease progression is driven by a vicious cycle of portal hypertension (PHT) and systemic inflammation (SI), in which cirrhosis-associated dysbiosis and impaired intestinal barrier function enable pathological bacterial translocation, which in turn perpetuates SI as the main driver and aggravates PHT. This mechanism is largely responsible for the development of complications such as spontaneous infections, hepatic encephalopathy, and acute-on-chronic liver failure (ACLF). A deeper understanding of these interactions not only underpins the rational use of established therapies but also opens up new perspectives for diagnostic and therapeutic strategies aiming to restore gut-liver homeostasis.

Liver failure is associated with severe lipid alterations, including pronounced reductions of high-density lipoprotein cholesterol (HDL-C) levels that are also of prognostic value. In the present study, we developed an optimized prognostic model based on HDL-C and other readily available blood parameters for survival prediction in patients with acutely decompensated (AD) cirrhosis. We measured HDL-C in biobanked plasma samples of patients recruited from the large prospective CANONIC and PREDICT cohorts. Multivariable competing risk analysis was performed with death as the event of interest and liver transplantation (LT) as the competing risk. Cox proportional hazards regression was used to construct a new prognostic model, and its performance was evaluated using the C-index and compared with other prognostic scores using the Integrated Discrimination Index statistics test. We analyzed 1035 patients with AD/ACLF (median age 59 y; 70% male; ACLF at inclusion 20%; etiology alcohol 59%). Multivariable analysis yielded 6 independent prognostic variables associated with 90-day survival: age, HDL-C, creatinine, sodium, WBC, and INR, which were incorporated in a new prognostic model termed CLIF-C HDL score. The new model showed superior discrimination ability for the prediction of 90-day mortality by C-index of 0.768 for CLIF-C HDL score versus 0.735 for MELD-Na ( p <0.001) versus 0.738 for MELD 3.0 ( p <0.001). This superior performance of the CLIF-C HDL score was confirmed in 2 external validation cohorts (Turin, n=338; Vienna, n=185). The new prognostic CLIF-C HDL score yields superior accuracy for the prediction of short-term mortality in AD cirrhosis as compared with other prognostic scores.