Section of Pediatric Surgery, Pediatric Liver and Gut Research Group, Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, P.O. Box 281, 00029 HUS Helsinki, Finland.
Pediatric Liver and Gut Research Group, Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Semin Pediatr Surg. 2020 Aug;29(4):150943. doi: 10.1016/j.sempedsurg.2020.150943. Epub 2020 Jul 24.
Several patient and treatment related factors significantly modify outcomes of biliary atresia. The extremely variable prognosis mandates intensive postoperative monitoring following portoenterostomy. Accurate prediction of outcome and progression of liver injury would enable individualized treatment and follow-up protocols, patient counseling and meaningful stratification of patients into clinical trials. While results on most biomarkers of cholestasis, hepatocyte function, fibrosis and inflammation studied so far are inconsistent or have not been validated in independent patient cohorts, postoperative serum bilirubin level 3 months after portoenterostomy remains the most accurate clinically feasible predictor of native liver survival. Although liver stiffness and a novel marker of cholangiocyte integrity, serum matrix metalloproteinase-7, correlate with liver fibrosis and may discriminate biliary atresia from other causes of neonatal cholestasis, further information on their ability to predict portoenterostomy outcomes is needed. Recent gene expression profiling has shown promise in overcoming the sampling error associated with histological quantification of liver fibrosis, and provides an important possibility to stratify patients for clinical trials according to the prognosis of native liver survival already preoperatively. As activity and extent of ductular reaction is linked with progression of liver fibrosis in cholangiopathies, further research is also warranted to evaluate predictive value of ductular reaction, matrix metalloproteinase-7 and the underlying gene expression signatures in relation to circulating bile acids in biliary atresia. Discovery of accurate predictive tools will ultimately increase our understanding of the unpredictable response to surgery and pathophysiology of progressive liver injury in biliary atresia.
许多患者和治疗相关因素显著改变胆道闭锁的结局。由于预后差异极大，因此在进行门腔分流术后需要进行密集的术后监测。准确预测结局和肝损伤进展将能够实现个体化治疗和随访方案、患者咨询，并将患者有意义地分层纳入临床试验。尽管迄今为止研究的大多数胆汁淤积、肝细胞功能、纤维化和炎症的生物标志物的结果不一致，或者尚未在独立患者队列中得到验证，但门腔分流术后 3 个月的血清胆红素水平仍然是预测肝固有生存最准确的临床可行预测指标。尽管肝硬度和一种新的胆管细胞完整性标志物，血清基质金属蛋白酶-7，与肝纤维化相关，并且可以区分胆道闭锁与其他新生儿胆汁淤积的原因，但仍需要进一步了解它们预测门腔分流术结局的能力。最近的基因表达谱分析显示有希望克服与肝纤维化组织学定量相关的取样误差，并为根据肝固有生存的预后在术前对患者进行临床试验分层提供了重要可能性。由于胆管反应的活性和程度与胆管病中的肝纤维化进展相关，因此还需要进一步研究以评估胆管反应、基质金属蛋白酶-7 以及与胆道闭锁相关的循环胆汁酸的潜在基因表达特征的预测价值。发现准确的预测工具将最终增加我们对手术反应不可预测性以及胆道闭锁中进行性肝损伤的病理生理学的理解。
