代偿期肝硬化患者和大鼠模型的病因特异性炎症模式。

IF 4 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
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
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引用次数: 0

摘要

背景:肝硬化与促炎症环境有关:目的:分析代偿期肝硬化动物模型和患者的病因特异性炎症模式:在肝硬化大鼠模型(硫代乙酰胺[TAA;n = 12];胆碱缺乏性高脂饮食[CDHFD;n = 12];胆管结扎[BDL;n = 16])中测量门静脉压力(PP)、纤维化(胶原比例面积[CPA])和肝脏炎症。还包括接受肝静脉压力梯度(HVPG)测量的肝硬化患者(酒精相关肝病[ALD;n = 67];代谢功能障碍相关性脂肪性肝炎[MASH;n = 50];胆汁淤积性肝病[原发性胆汁性胆管炎[PBC]/原发性硬化性胆管炎[PSC];n = 22]):结果:在大鼠中,CDHFD 的肝脏促炎基因表达量最高,而 TAA 的表达量最低,尽管 PP 水平相当。在所有动物模型中,Tnfa/Il6 与 CPA 呈正相关,Mcp1 与 PP 升高呈正相关。在 TAA/CDHFD 中,Mcp1 也与 CPA 的增加有关。Mcp1/Cxcl1 与转氨酶呈模型无关的正相关。Il1b与BDL的CPA/PP呈正相关,与CDHFD的转氨酶呈正相关。在患者中,与 ALD 或 PBC/PSC 相比,MASH 患者的 CRP/IL-6 更低,与肝功能无关。ALD患者的IgA/IgG最高,补体因子最低。更明显的全身炎症主要与 ALD/MASH 中更高的 HVPG 有关:结论:在所有肝病病因中,促炎症通路都会上调,但它们与肝纤维化和门静脉高压的关系却各不相同。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
Digestive and Liver Disease
Digestive and Liver Disease 医学-胃肠肝病学
CiteScore
6.10
自引率
2.20%
发文量
632
审稿时长
19 days
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.
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