The 75th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) took place in San Diego, USA, from November 15 to 19, 2024. Six research projects from the Department of Gastroenterology at West China Hospital of Sichuan University, led by Dr. Li Yang and Dr. Xuefeng Luo, were featured in oral presentations and poster sessions, garnering significant attention. This article summarizes their key findings in cirrhosis, liver fibrosis, and autoimmune hepatitis (AIH).Part 1: Cirrhosis
Extracellular Vesicles Secreted by Injured Hepatocytes Drive Cirrhosis-Associated Muscle Wasting Through the mtDNA-cGAS-STING Axis (Oral Presentation)
• Authors: Fan Xiaoli, Peng Yunke, Li Bo
• Corresponding Authors: Yang Li, Liu Jingping
Sarcopenia, a severe complication of cirrhosis, currently lacks effective treatments. Chronic inflammation plays a pivotal role in the pathology of muscle atrophy, but the precise mechanisms of liver-mediated muscle inflammation remain unclear. This study explored how extracellular vesicles (EVs) from damaged hepatocytes exacerbate muscle inflammation during cirrhosis.
Using mouse models of carbon tetrachloride injection and bile duct ligation, researchers observed that mitochondrial damage in hepatocytes triggers the release of EVs enriched in mitochondrial DNA (mtDNA). These EVs activate the STING signaling pathway in muscle macrophages, leading to inflammatory damage and muscle wasting. Knocking out Rab27a in the liver or using STING inhibitors significantly reduced muscle inflammation and atrophy in cirrhotic mice. Furthermore, elevated levels of mtDNA-enriched EVs were found in cirrhotic patients, correlating with disease severity.
Conclusion: Targeting the secretion of hepatic EVs or the STING pathway may offer potential therapeutic strategies for preventing cirrhosis-associated sarcopenia.
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Cardiac Decompensation Post-TIPS in Cirrhosis Patients (Poster Presentation)
• Authors: Du Shumei
• Corresponding Author: Luo Xuefeng
Transjugular intrahepatic portosystemic shunt (TIPS) is effective for portal hypertension complications but raises concerns about post-TIPS heart failure. In a cohort of 140 patients, no cases of heart failure were observed post-TIPS during a median follow-up of six months. However, 67.1% developed edema, and echocardiographic parameters indicated minimal cardiac function changes.
Conclusion: Cardiac decompensation is rare post-TIPS, and specialized stents may mitigate risks associated with TIPS.
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Specialized TIPS Stents Reduce Hepatic Encephalopathy Risk (Poster Presentation)
• Authors: Du Shumei
• Corresponding Author: Luo Xuefeng
This study compared the Viatorr and Fluency stents in 1,077 cirrhotic patients undergoing TIPS. The Viatorr stent significantly reduced the two-year cumulative incidence of hepatic encephalopathy (26.4% vs. 34.3%, P=0.018) and shunt dysfunction (2.2% vs. 7.5%, P=0.037).
Conclusion: Specialized stents, such as Viatorr, should be prioritized in cirrhotic patients undergoing TIPS to improve outcomes.
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Part 2: Liver Fibrosis
Chromatin Accessibility in Hepatic Stellate Cells: Mechanisms Underlying Liver Fibrosis (Poster Presentation)
• Authors: Jia Tingting, Shen Yi
• Corresponding Authors: Yang Li, Jiang Hao
Hepatic stellate cell (HSC) activation drives liver fibrosis. Using various HSC activation models, researchers identified 12 transcription factors, including Runx2, Creb5, and Smad3, as key mediators of chromatin accessibility changes during HSC activation.
Conclusion: These transcription factors are potential therapeutic targets for treating liver fibrosis.
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Part 3: Autoimmune Hepatitis (AIH)
The CCL2/CCR2 Axis in AIH: Inflammatory Mechanisms and Therapeutic Potential (Poster Presentation)
• Authors: Fan Xiaoli, Yang Fan
• Corresponding Authors: Yang Li, Liu Jingping
This study elucidated the role of the CCL2/CCR2 axis in recruiting inflammatory monocytes to the liver, exacerbating AIH. Blocking CCR2 using extracellular vesicles (EVs) derived from M2 macrophages effectively reduced liver damage in mouse models.
Conclusion: Targeting the CCL2/CCR2 axis via engineered EVs offers a promising therapeutic avenue for AIH.
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Expert Profile: Professor Luo Xuefeng
• Affiliation: Sichuan University, West China Hospital
• Specialization: Cirrhosis, portal hypertension, and interventional liver therapies
• Accomplishments:
• Over 60 SCI-indexed publications in leading journals like Hepatology
• Key contributor to major guidelines, including “Baveno VII Portal Hypertension Consensus”
• Awards: UEG “Best Abstract Presentation Prize,” “BEST of DDW,” and several national honors
These groundbreaking studies highlight the contributions of Professors Yang Li and Luo Xuefeng’s team to advancing the understanding and management of liver diseases.
