Pediatric Liver Center, Digestive Health Institute, Children's Hospital Colorado, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine, Box B290, 13123 E. 16th Ave., Aurora, CO 80045, USA.
Pediatric Liver Center, Digestive Health Institute, Children's Hospital Colorado, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine, Box B290, 13123 E. 16th Ave., Aurora, CO 80045, USA; Colorado Clinical and Translational Sciences Institute, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Semin Pediatr Surg. 2020 Aug;29(4):150945. doi: 10.1016/j.sempedsurg.2020.150945. Epub 2020 Jul 23.
Neonatal cholestasis is characterized by conjugated hyperbilirubinemia in the newborn and young infant and is a sign common to over 100 hepatobiliary and/or metabolic disorders. A timely evaluation for its etiology is critical in order to quickly identify treatable causes such as biliary atresia, many of which benefit from early therapy. An expanding group of molecularly defined disorders involving bile formation, canalicular transporters, tight junction proteins and inborn errors of metabolism are being continuously discovered because of advances in genetic testing and bioinformatics. The advent of next generation sequencing has transformed our ability to test for multiple genes and whole exome or whole genome sequencing within days to weeks, enabling rapid and affordable molecular diagnosis for disorders that cannot be directly diagnosed from standard blood tests or liver biopsy. Thus, our diagnostic algorithms for neonatal cholestasis are undergoing transformation, moving genetic sequencing to earlier in the evaluation pathway once biliary atresia, "red flag" disorders and treatable disorders are excluded. Current therapies focus on promoting bile flow, reducing pruritus, ensuring optimal nutrition, and monitoring for complications, without addressing the underlying cause of cholestasis in most instances. Our improved understanding of bile formation and the enterohepatic circulation of bile acids has led to emerging therapies for cholestasis which require appropriate pediatric clinical trials. Despite these advances, the cause and optimal therapy for biliary atresia remain elusive. The goals of this review are to outline the etiologies, diagnostic pathways and current and emerging management strategies for neonatal cholestasis.
新生儿胆汁淤积症的特征是新生儿和婴儿的结合胆红素血症，是 100 多种肝胆和/或代谢疾病的共同标志。及时评估其病因对于快速识别可治疗的病因至关重要，例如胆道闭锁，其中许多病因受益于早期治疗。由于遗传测试和生物信息学的进步，不断发现涉及胆汁形成、胆管转运蛋白、紧密连接蛋白和先天性代谢错误的分子定义疾病。下一代测序的出现改变了我们在几天到几周内测试多个基因和整个外显子或全基因组测序的能力，使无法直接从标准血液检查或肝活检诊断的疾病能够快速且负担得起地进行分子诊断。因此，我们对新生儿胆汁淤积症的诊断算法正在发生转变，一旦排除胆道闭锁、“红旗”疾病和可治疗疾病，遗传测序就会更早地纳入评估途径。目前的治疗方法主要集中在促进胆汁流动、减少瘙痒、确保最佳营养和监测并发症上，而大多数情况下都没有解决胆汁淤积的根本原因。我们对胆汁形成和胆汁酸的肠肝循环的理解的提高导致了针对胆汁淤积症的新兴治疗方法，这些方法需要进行适当的儿科临床试验。尽管取得了这些进展，但胆道闭锁的病因和最佳治疗方法仍然难以捉摸。本篇综述的目的是概述新生儿胆汁淤积症的病因、诊断途径以及当前和新兴的管理策略。
