(Press-News.org) A newly published review in eGastroenterology compiles recent research on alcohol-associated liver disease (ALD), offering an overview of its pathogenesis and efforts to better understand this condition. ALD, caused by excessive alcohol consumption, remains a significant contributor to liver-related mortality worldwide. Effective treatments are still limited, underscoring the need for a deeper understanding of its mechanisms. This review summarizes findings on the cellular, molecular, and systemic processes involved in ALD progression, with a focus on liver cell interactions, immune responses, and inter-organ communication.
The review examines how alcohol metabolism affects liver function, focusing on the roles of oxidative stress and inflammation in driving liver injury. Alcohol metabolism in hepatocytes generates reactive oxygen species (ROS) and toxic byproducts such as acetaldehyde, which can damage liver cells and trigger immune responses. Activation of Kupffer cells (liver-resident macrophages) and hepatic stellate cells (HSCs) contributes to inflammation and fibrosis, which are key features of ALD progression. The review highlights these pathways as areas of interest for future research.
A notable focus of the review is the role of extracellular vesicles (EVs) in intercellular communication. These nanoscale particles, released by damaged liver cells, carry molecular signals that can influence both neighboring and distant cells. EVs are implicated in modulating immune responses, activating HSCs, and promoting fibrosis, suggesting their involvement in ALD progression. The review also discusses recent studies identifying EVs as potential biomarkers for early diagnosis and as possible targets for therapeutic intervention.
The review discusses the gut-liver axis as an important pathway in the development of ALD. Alcohol-induced changes in gut microbiota, known as dysbiosis, can increase intestinal permeability, allowing bacterial products like lipopolysaccharides (LPS) to reach the liver. These microbial products may activate inflammatory pathways, contributing to liver injury. This interaction between the gut and liver underscores the systemic nature of ALD and suggests potential avenues for therapies that address both gut and liver health.
The review discusses the role of cytokines, signaling molecules involved in regulating inflammation and immune responses, in ALD. Pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-17, contribute to liver injury by promoting inflammation and recruiting immune cells. Anti-inflammatory cytokines, like IL-10, work to counteract this response but may be insufficient during chronic alcohol exposure. Exploring the interplay between these opposing forces could provide insights into potential strategies for modulating the immune response to reduce liver damage.
The review also considers the broader impact of ALD, highlighting its effects on other organs and systems beyond the liver. It discusses the interactions between the liver, gut, adipose tissue, and the immune system. For instance, free fatty acids and adipokines released from adipose tissue may contribute to hepatic steatosis and inflammation. These connections suggest the importance of a comprehensive approach to understanding and addressing ALD.
This review provides a comprehensive synthesis of current knowledge, summarizing data from various studies to offer an overview of the pathogenesis of ALD and identify areas where further research is needed. The perspective presented aims to inform future studies and contribute to the development of diagnostic and therapeutic approaches.
“This review is a testament to the progress made in understanding ALD,” said Dr. Hui Gao, the first author of the review. “It highlights not only the complexity of the disease but also the opportunities for intervention through targeted therapies.”
See the article:
Gao H, Jiang Y, Zeng G, et al. Cell-to-cell and organ-to-organ crosstalk in the pathogenesis of alcohol-associated liver disease. eGastroenterology 2024;2:e100104. doi:10.1136/egastro-2024-100104
About eGastroenterology
eGastroenterology is a new, open-access, and open peer-reviewed BMJ Journal, which focuses on basic, clinical, translational, and evidence-based medicine research in all areas of gastroenterology (including hepatology, pancreatology, esophagology, and gastrointestinal surgery). eGastroenterology is now indexed by DOAJ, Dimensions, OpenAlex, ROAD, and COPE, with more to come!
For more information, please visit: egastroenterology.bmj.com and follow us on Twitter (@eGastro_BMJ).
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