Inflammation remains a dynamic component of portal hypertension in regressive alcohol‐related cirrhosis

作者：Benedikt Hofer, Benedikt Simbrunner, Philipp Königshofer, Ksenia Brusilovskaya, Oleksandr Petrenko, Vlad Țâru, Thomas Sorz‐Nechay, Kerstin Zinober, Katharina Regnat, Georg Semmler, Carolin Lackner, Michael Trauner, Mattias Mandorfer, Philipp Schwabl, Thomas Reiberger · 发表于：United European Gastroenterology Journal · 年份：2024 · DOI：10.1002/ueg2.12643 · 被引用次数：8 · 研究领域：Liver Disease and Transplantation、Alcohol Consumption and Health Effects、Liver Disease Diagnosis and Treatment

BACKGROUND: Portal hypertension (PH) resulting from static and dynamic intrahepatic changes drives liver-related complications even after removing the underlying aetiological factor. OBJECTIVE: We investigated the impact of inflammation on the dynamic component of PH during disease regression in animal models of toxin-induced cirrhosis and patients with alcohol-related cirrhosis. METHODS: In mice, cirrhosis was induced via toxin application for 12 weeks followed by toxin-withdrawal allowing for one or 2 weeks of regression. Furthermore, 128 patients with alcohol-related cirrhosis and alcohol abstinence undergoing same-day hepatic venous pressure gradient (HVPG) and liver stiffness measurement (LSM) were included. The influence of inflammation on the dynamic PH component was assessed using linear models. Specifically, we explored proinflammatory changes in mice/patients in whom the measured portal pressure (PP)/HVPG was significantly higher than the PP/HVPG expected from the static PH component (histological collagen proportionate area [CPA; %] in mice, LSM in patients). RESULTS: In mice, toxin discontinuation induced a significant decrease in PP, CPA, histological hepatic inflammation and hepatic expression of proinflammatory genes (Tnfa, Il6, Cxcl1, Mcp1; all p < 0.05 for one/2 week regression vs. peak disease). Similarly, prolonged abstinence in alcohol-related cirrhosis was linked to lower HVPG/LSM and longer abstinence was correlated to lower C-reactive protein (CRP), IL-...