Benedikt Silvester Hofer, Benedikt Simbrunner, Philipp Königshofer, Ksenia Brusilovskaya, Oleksandr Petrenko, Vlad Taru, Thomas Sorz, Kerstin Zinober, Georg Semmler, Stefan G Kauschke, Larissa Pfisterer, Michael Trauner, Mattias Mandorfer, Philipp Schwabl, Thomas Reiberger
{"title":"代偿期肝硬化患者和大鼠模型的病因特异性炎症模式。","authors":"Benedikt Silvester Hofer, Benedikt Simbrunner, Philipp Königshofer, Ksenia Brusilovskaya, Oleksandr Petrenko, Vlad Taru, Thomas Sorz, Kerstin Zinober, Georg Semmler, Stefan G Kauschke, Larissa Pfisterer, Michael Trauner, Mattias Mandorfer, Philipp Schwabl, Thomas Reiberger","doi":"10.1016/j.dld.2024.09.006","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Cirrhosis is associated with a proinflammatory environment.</p><p><strong>Aims: </strong>To analyse aetiology-specific inflammation patterns in compensated cirrhosis in animal models and patients.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Proinflammatory pathways are upregulated across all liver disease aetiologies, yet their association with fibrosis and portal hypertension can vary.</p>","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":" ","pages":""},"PeriodicalIF":4.0000,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Aetiology-specific inflammation patterns in patients and rat models of compensated cirrhosis.\",\"authors\":\"Benedikt Silvester Hofer, Benedikt Simbrunner, Philipp Königshofer, Ksenia Brusilovskaya, Oleksandr Petrenko, Vlad Taru, Thomas Sorz, Kerstin Zinober, Georg Semmler, Stefan G Kauschke, Larissa Pfisterer, Michael Trauner, Mattias Mandorfer, Philipp Schwabl, Thomas Reiberger\",\"doi\":\"10.1016/j.dld.2024.09.006\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Cirrhosis is associated with a proinflammatory environment.</p><p><strong>Aims: </strong>To analyse aetiology-specific inflammation patterns in compensated cirrhosis in animal models and patients.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Proinflammatory pathways are upregulated across all liver disease aetiologies, yet their association with fibrosis and portal hypertension can vary.</p>\",\"PeriodicalId\":11268,\"journal\":{\"name\":\"Digestive and Liver Disease\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2024-09-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Digestive and Liver Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.dld.2024.09.006\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Digestive and Liver Disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.dld.2024.09.006","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Aetiology-specific inflammation patterns in patients and rat models of compensated cirrhosis.
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 across all liver disease aetiologies, yet their association with fibrosis and portal hypertension can vary.
期刊介绍:
Digestive and Liver Disease is an international journal of Gastroenterology and Hepatology. It is the official journal of Italian Association for the Study of the Liver (AISF); Italian Association for the Study of the Pancreas (AISP); Italian Association for Digestive Endoscopy (SIED); Italian Association for Hospital Gastroenterologists and Digestive Endoscopists (AIGO); Italian Society of Gastroenterology (SIGE); Italian Society of Pediatric Gastroenterology and Hepatology (SIGENP) and Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD).
Digestive and Liver Disease publishes papers on basic and clinical research in the field of gastroenterology and hepatology.
Contributions consist of:
Original Papers
Correspondence to the Editor
Editorials, Reviews and Special Articles
Progress Reports
Image of the Month
Congress Proceedings
Symposia and Mini-symposia.