小儿肝性脑病（HE）的病理生理机制尚不清楚。与HE相关的各种血清生物标志物可能有助于了解其病理学，但它们在诊断和预后的临床实践中的使用和解释仍未确定。我们旨在调查报道的血清生物标志物与儿童HE存在和程度的相关性。我们在PubMed、Embase、Lilacs和Scopus上对涉及儿童的HE的新型血清生物标志物和细胞因子进行研究的系统评价。我们利用Covidence对每项研究的摘要和正文进行两个独立评审者的评审。我们评审了2824份独特的出版物；其中15份符合标准。报道的生物标志物类别包括炎性细胞因子、氨基酸代谢产物、微量元素和维生素，以及肝和神经生物标记物。在19种个体生物标志物中，只有五种在多个研究中被测量。升高的白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）最常见地报道与HE相关。值得注意的是，我们发现仅研究小儿的IL-6和TNF-α水平明显低于混合年龄的研究。总体而言，我们观察到高偏倚和对我们的审查问题适用性差。我们遇到了少量的以小儿为重点的研究，也很少进行低偏倚的研究设计。研究的生物标志物涵盖了广泛的类别，并暗示了与HE有潜在有用的相关性。进一步进行设计良好的前瞻性生物标志物研究有必要更好地阐明小儿HE的发病机制并改善早期检测和临床护理。版权所有©2023年欧洲小儿胃肠病、肝病和营养学协会及北美小儿胃肠病、肝病和营养学协会。

The pathophysiology of pediatric hepatic encephalopathy (HE) is not well understood. Various serum biomarkers associated with HE may provide insight into its pathology, but their use and interpretation in clinical practice for diagnosis and prognostication remain undetermined. We sought to investigate reported correlations of serum biomarkers with presence and degree of HE in children.We conducted a systematic review of studies examining novel serum biomarkers and cytokines in association with HE that included children on PubMed, Embase, Lilacs, and Scopus. We utilized Covidence for abstract and text review by two independent reviewers for each study.We reviewed 2,824 unique publications; 15 met criteria for inclusion. Categories of biomarkers reported were inflammatory cytokines, products of amino acid metabolism, trace elements and vitamins, and hepatic and neuro biomarkers. Of 19 individual biomarkers, only five were measured in more than one study. Elevations in interleukin-6 (IL-6) and tumor necrosis factor- alpha (TNF-alpha) were most commonly reported as associated with HE. Notably, we observed lower average IL-6 and TNF-alpha levels in pediatric-only studies compared to mixed age studies. Overall, high bias and poor applicability to our review question was observed. We encountered low numbers of studies with pediatric focus, and few conducted with low bias study designs.Investigated biomarkers span a large range of categories and suggest potentially useful correlations with HE. Further well-designed prospective biomarker research is necessary to better elucidate the pathogenesis of HE in children and improve early detection and clinical care.Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.