Alonso Estella M, Horslen Simon P, Behrens Edward M, Doo Edward
Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
Department of Pediatrics at the University of Washington School of Medicine, Seattle Children's Hospital, Seattle, WA.
Hepatology. 2017 Mar;65(3):1026-1037. doi: 10.1002/hep.28944. Epub 2017 Jan 6.
Pediatric acute liver failure (PALF) is a potentially devastating condition that occurs in previously healthy children of all ages and frequently leads to a rapid clinical deterioration. An identified cause for liver injury is lacking in approximately 30% of cases. Children with undetermined diagnosis have lower spontaneous survival and higher rates of transplantation and death than other diagnostic groups. A single-day workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases brought together clinicians and basic scientists to integrate aligned research findings and develop a foundation for new mechanistic studies and future treatment trials. The clinical phenotype of indeterminate PALF shares important similarities to the hyperinflammatory state characteristic of hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). A failure of cytotoxic T cells to limit or contract inflammatory responses may propagate injury and lead to a local and systemic milieu that does not support normal hepatic regeneration. Evidence was presented that bone marrow (BM)-derived Sinusoidal endothelial cell PROgenitor Cells (sprocs) play a vital role in hepatic regeneration. Overwhelming systemic inflammatory responses may suppress mobilization of BM sprocs and dampen hepatic recovery.
Experience gained through treatment trials of HLH and MAS in childhood may inform study design for therapy of PALF. Successful approaches to limiting neuroinflammation through reduction of systemic inflammation and standardized neuroprotection protocols that limit glial injury could significantly improve intact survival. Finally, given that PALF is a rare disease, investigative efforts must include broad multicenter collaboration and careful stewardship of biorepository specimens. (Hepatology 2017;65:1026-1037).
小儿急性肝衰竭（PALF）是一种潜在的毁灭性疾病，可发生于各年龄段之前健康的儿童，常导致临床迅速恶化。约30%的病例缺乏明确的肝损伤病因。诊断未明的儿童比其他诊断组的自发存活率更低，移植率和死亡率更高。由美国国立糖尿病、消化和肾脏疾病研究所主办的为期一天的研讨会汇聚了临床医生和基础科学家，整合一致的研究结果，并为新的机制研究和未来治疗试验奠定基础。不明原因PALF的临床表型与噬血细胞性淋巴组织细胞增生症（HLH）和巨噬细胞活化综合征（MAS）的高炎症状态有重要相似之处。细胞毒性T细胞未能限制或控制炎症反应可能会加重损伤，并导致局部和全身环境不利于正常肝脏再生。有证据表明，骨髓（BM）来源的窦状内皮细胞祖细胞（sprocs）在肝脏再生中起关键作用。压倒性的全身炎症反应可能会抑制BM sprocs的动员并阻碍肝脏恢复。
通过儿童HLH和MAS治疗试验获得的经验可能为PALF治疗的研究设计提供参考。通过减轻全身炎症来限制神经炎症的成功方法以及限制神经胶质损伤的标准化神经保护方案可能会显著提高完整存活率。最后，鉴于PALF是一种罕见疾病，研究工作必须包括广泛的多中心合作以及对生物样本库标本的精心管理。（《肝脏病学》2017年；65:1026 - 1037）
