肠外营养相关肝损伤:临床意义和机理认识。

IF 3.4 3区 医学 Q2 TOXICOLOGY
Milos Mihajlovic, Zenzi Rosseel, Elisabeth De Waele, Mathieu Vinken
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引用次数: 0

摘要

肠功能衰竭相关性肝病(IFALD)是接受肠外营养(PN)的患者中比较常见的一种并发症。IFALD 可表现为不同类型的肝损伤,包括脂肪变性、胆汁淤积和肝纤维化,在某些情况下可导致肝功能衰竭。IFALD 的发病和进展在很大程度上取决于患者和 PN 相关的各种风险因素。尽管仍在研究中,但已提出了几种机制。肝损伤可能源于热量超负荷、营养缺乏和毒性,以及植物甾醇含量和脂质乳剂中含有的欧米伽-6 脂肪酸与欧米伽-3 脂肪酸的比例。其他机制包括胆汁酸代谢不成熟或有缺陷、急性心力衰竭、感染和败血症通过 Toll 样受体 4 和核因子 κB 炎症信号产生负面影响。此外,缺乏肠道喂养、肠道菌群失调和肠肝循环改变会影响类法尼x受体-成纤维细胞生长因子19轴,也会导致IFALD。可以采取各种最佳实践来最大限度地降低罹患 IFALD 的风险,如预防和处理中心管路感染和败血症、保留肠道长度、改用口服和肠内喂养、周期性 PN、避免过度喂养和以大豆油为基础的脂质配方以及避免使用肝毒性物质。因此,本综述全面概述了 IFALD 所固有的所有相关方面。为了深入了解肝毒性的分子发病机制、降低 IFALD 的发病率并鼓励安全使用 PN,我们需要进一步开展以临床观察、转化模型和先进毒理学知识框架为重点的研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Parenteral nutrition-associated liver injury: clinical relevance and mechanistic insights.

Intestinal failure-associated liver disease (IFALD) is a relatively common complication in individuals receiving parenteral nutrition (PN). IFALD can be manifested as different types of liver injury, including steatosis, cholestasis, and fibrosis, and could result in liver failure in some cases. The onset and progression of IFALD are highly dependent on various patient and PN-related risk factors. Despite still being under investigation, several mechanisms have been proposed. Liver injury can originate due to caloric overload, nutrient deficiency, and toxicity, as well as phytosterol content, and omega-6 to omega-3 fatty acids ratio contained in lipid emulsions. Additional mechanisms include immature or defective bile acid metabolism, acute heart failure, infections, and sepsis exerting negative effects via Toll-like receptor 4 and nuclear factor κB inflammatory signaling. Furthermore, lack of enteral feeding, gut dysbiosis, and altered enterohepatic circulation that affect the farnesoid x receptor-fibroblast growth factor 19 axis can also contribute to IFALD. Various best practices can be adopted to minimize the risk of developing IFALD, such as prevention and management of central line infections and sepsis, preservation of intestine's length, a switch to oral and enteral feeding, cyclic PN, avoidance of overfeeding and soybean oil-based lipid formulations, and avoiding hepatotoxic substances. The present review thus provides a comprehensive overview of all relevant aspects inherent to IFALD. Further research focused on clinical observations, translational models, and advanced toxicological knowledge frameworks is needed to gain more insight into the molecular pathogenesis of hepatotoxicity, reduce IFALD incidence, and encourage the safe use of PN.

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来源期刊
Toxicological Sciences
Toxicological Sciences 医学-毒理学
CiteScore
7.70
自引率
7.90%
发文量
118
审稿时长
1.5 months
期刊介绍: The mission of Toxicological Sciences, the official journal of the Society of Toxicology, is to publish a broad spectrum of impactful research in the field of toxicology. The primary focus of Toxicological Sciences is on original research articles. The journal also provides expert insight via contemporary and systematic reviews, as well as forum articles and editorial content that addresses important topics in the field. The scope of Toxicological Sciences is focused on a broad spectrum of impactful toxicological research that will advance the multidisciplinary field of toxicology ranging from basic research to model development and application, and decision making. Submissions will include diverse technologies and approaches including, but not limited to: bioinformatics and computational biology, biochemistry, exposure science, histopathology, mass spectrometry, molecular biology, population-based sciences, tissue and cell-based systems, and whole-animal studies. Integrative approaches that combine realistic exposure scenarios with impactful analyses that move the field forward are encouraged.
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