Neonatal cholestasis: emerging molecular diagnostics and potential novel therapeutics
新生儿胆汁淤积：新兴的分子诊断和潜在的新疗法
Neonatal cholestasis is a group of rare disorders of impaired bile flow characterized by conjugated hyperbilirubinaemia in the newborn and young infant. Neonatal cholestasis is never physiological but rather is a sign of hepatobiliary and/or metabolic disorders, some of which might be fatal if not identified and treated rapidly. A step-wise timely evaluation is essential to quickly identify those causes amenable to treatment and to offer accurate prognosis. The aetiology of neonatal cholestasis now includes an expanding group of molecularly defined entities with overlapping clinical presentations. In the past two decades, our understanding of the molecular basis of many of these cholestatic diseases has improved markedly. Simultaneous next-generation sequencing for multiple genes and whole-exome or whole-genome sequencing now enable rapid and affordable molecular diagnosis for many of these disorders that cannot be directly diagnosed from standard blood tests or liver biopsy. Unfortunately , despite these advances, the aetiology and optimal therapeutic approach of the most common of these disorders, biliary atresia, remain unclear. The goals of this Review are to discuss the aetiologies, algorithms for evaluation and current and emerging therapeutic options for neonatal cholestasis.
新生儿胆汁淤积是一组罕见的胆汁受损疾病，其特征在于新生儿和幼儿的结合性高胆红素血症。新生儿胆汁淤积从来不是生理性的，而是肝胆和/或代谢紊乱的征兆，如果不能快速识别和治疗，其中一些可能是致命的。逐步及时评估对于快速确定适合治疗的原因并提供准确的预后至关重要。新生儿胆汁淤积的病因现在包括一组扩大的分子定义实体，具有重叠的临床表现。在过去的二十年中，我们对许多这些胆汁淤积性疾病的分子基础的理解有了显着的改善。对于多种基因和全外显子组或全基因组测序的同时下一代测序，现在能够对许多这些无法通过标准血液检查或肝脏活组织检查直接诊断的疾病进行快速且经济的分子诊断。 不幸的是，尽管有这些进展，但最常见的这些疾病，胆道闭锁的病因和最佳治疗方法仍不清楚。本评价的目的是讨论病因，评估算法以及新生儿胆汁淤积的当前和新兴治疗方案。