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

Digestive and Liver Disease Pub Date : 2025-02-01 DOI:10.1016/j.dld.2024.09.006

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。

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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 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.