Aetiology-specific inflammation patterns in patients and rat models of compensated cirrhosis

作者：Benedikt Hofer, Benedikt Simbrunner, Philipp Königshofer, Ksenia Brusilovskaya, Oleksandr Petrenko, Vlad Țâru, Thomas Sorz, Kerstin Zinober, Georg Semmler, Stefan G. Kauschke, Larissa Pfisterer, Michael Trauner, Mattias Mandorfer, Philipp Schwabl, Thomas Reiberger · 发表于：Digestive and Liver Disease · 年份：2024 · DOI：10.1016/j.dld.2024.09.006 · 被引用次数：5 · 研究领域：Liver Disease and Transplantation、Liver Disease Diagnosis and Treatment、Liver Diseases and Immunity

BACKGROUND: Cirrhosis is associated with a proinflammatory environment. AIMS: To analyse aetiology-specific inflammation patterns in compensated cirrhosis in animal models and patients. METHODS: Portal pressure (PP), fibrosis (collagen proportionate area [CPA]) and hepatic inflammation were measured in cirrhotic rat models (thioacetamide [TAA;n = 12]; choline-deficient high-fat diet [CDHFD;n = 12]; bile duct ligation [BDL;n = 16]). Compensated cirrhotic patients (alcohol-related liver disease [ALD;n = 67]; metabolic dysfunction-associated steatohepatitis [MASH;n = 50]; cholestatic liver disease [primary biliary cholangitis [PBC]/primary sclerosing cholangitis [PSC];n = 22]) undergoing hepatic venous pressure gradient (HVPG) measurement were included. RESULTS: In rats, hepatic proinflammatory gene expression was highest in CDHFD and lowest in TAA, despite comparable PP levels. Across all animal models, Tnfa/Il6 correlated positively with CPA, and Mcp1 with elevated PP. Mcp1 was also associated with increased CPA in TAA/CDHFD. Mcp1/Cxcl1 showed a model-independent positive correlation to transaminases. Il1b correlated positively with CPA/PP in BDL and with transaminases in CDHFD. In patients, CRP/IL-6 were lower in MASH compared to ALD or PBC/PSC, regardless of hepatic function. IgA/IgG were highest and complement factors lowest in ALD. More pronounced systemic inflammation was linked to higher HVPG primarily in ALD/MASH. CONCLUSION: Proinflammatory pathways are upregulated acr...