Abi-Aad Sasha-Jane, Lovell Mark, Khalaf Racha T, Sokol Ronald J
Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of South Florida Morsani College of Medicine, Tampa, Florida.
Department of Pathology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado.
Semin Liver Dis. 2025 Mar;45(1):66-80. doi: 10.1055/a-2545-7370. Epub 2025 Feb 27.
Long-term parenteral nutrition (PN) has considerably improved the management of intestinal failure (IF) in children and adults, particularly those with short bowel syndrome; however, it carries a significant risk of hepatotoxicity, specifically, intestinal failure-associated liver disease (IFALD), also known as PN-associated liver disease. This review provides an update on the latest understanding of IFALD pathogenesis, emerging therapies, and ongoing challenges in the management of this complication. A number of factors are associated with the development of IFALD. PN lipid emulsions, phytosterol exposure, bacterial dysbiosis, an altered gut-liver axis, and episodes of sepsis disrupt bile acid homeostasis and promote liver inflammation in the active phase of IFALD, favoring the development of PN-associated cholestasis (PNAC) and the more chronic form of steatohepatitis with fibrosis. Based on the identification of pathophysiological pathways, potential therapies are being studied in preclinical and clinical trials, including lipid emulsion modifications; targeted therapies such as Farnesoid X receptor (FXR) and liver receptor homolog 1 (LRH-1) agonists, tumor necrosis factor inhibitors, glucagon-like peptide-2 analogs; microbiome modulation; and supplementation with choline and antioxidants. In conclusion, the pathogenesis of IFALD is complex, and PN dependence and liver injury remain challenging, particularly in patients with IF who cannot advance to enteral nutrition and be weaned off PN.
长期肠外营养（PN）显著改善了儿童和成人肠道衰竭（IF）的治疗管理，尤其是短肠综合征患者；然而，它具有显著的肝毒性风险，具体而言，即肠衰竭相关肝病（IFALD），也称为PN相关肝病。本综述提供了关于IFALD发病机制、新兴疗法以及该并发症管理中持续存在的挑战的最新认识。许多因素与IFALD的发生发展相关。PN脂质乳剂、植物甾醇暴露、肠道菌群失调、肠-肝轴改变以及脓毒症发作会破坏胆汁酸稳态，并在IFALD的活跃期促进肝脏炎症，从而有利于PN相关胆汁淤积（PNAC）以及更慢性的伴有纤维化的脂肪性肝炎的发展。基于病理生理途径的确定，正在临床前和临床试验中研究潜在疗法，包括脂质乳剂改良；靶向疗法，如法尼醇X受体（FXR）和肝脏受体同源物1（LRH-1）激动剂、肿瘤坏死因子抑制剂、胰高血糖素样肽-2类似物；微生物群调节；以及补充胆碱和抗氧化剂。总之，IFALD的发病机制复杂，PN依赖和肝损伤仍然具有挑战性，尤其是对于无法过渡到肠内营养并停用PN的IF患者。
