Department of Pediatric Surgery, Hannover Medical School, Hannover, Germany.
Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany.
Cytokine. 2018 Nov;111:382-388. doi: 10.1016/j.cyto.2018.09.010. Epub 2018 Oct 6.
Biliary atresia (BA) is a rare disease of unknown pathogenesis in infants characterized by an inflammatory, progressive destruction of the biliary system and deterioration of liver function. The standard treatment for BA is a Kasai-hepatoportoenterostomy (KPE). However, liver transplantation (LTX) becomes necessary in about 50-80% of cases. Therefore, some authors advocate for primary LTX in BA, but this would require early markers to predict which children would benefit from KPE or to show rapid progression to liver cirrhosis (RLC) instead.
Snap-frozen liver biopsies and sera samples of 57 infants with BA were collected during KPE. Clinical and follow-up data were assessed via the biliary atresia and related diseases registry (BARD-online.com). Protein-levels of 25 pro- and anti-inflammatory mediators of 49 infants were assessed via multiplex protein-immunoassay and analyzed by t-test as well as multidimensional principal component analysis.
22 different immunomodulatory mediators were detectable in livers of children with BA, while serum protein levels were very low to undetectable. Following KPE, 33 BA patients showed RLC that required early LTX, while 24 had favorable course of disease with long-term survival with native liver (SNL). There were no significant differences between RLC and SNL in terms of local (from liver samples) nor systemic (from sera) immunomodulatory mediators. Protein levels were much lower in sera than in livers without statistical correlation.
Our data suggest that local or systemic immunomodulatory mediators are unsuitable for predicting the disease course of BA. Thus, no deduction for optimal treatment strategy can be drawn. Collectively, we conclude that in BA, the degree of inflammation and protein microenvironment in the liver at the time-point of KPE are dismissible factors for the future course of disease.
婴儿先天性胆道闭锁（BA）是一种病因不明的罕见疾病，其特征为胆道的炎症性、进行性破坏和肝功能恶化。BA 的标准治疗方法是葛西肝门肠吻合术（KPE）。然而，约 50-80%的病例需要进行肝移植（LTX）。因此，一些作者主张对 BA 进行原发性 LTX，但这需要早期标志物来预测哪些患儿将从 KPE 中受益，或者显示出快速进展为肝硬化（RLC）。
在 KPE 期间收集了 57 名 BA 婴儿的冷冻肝活检和血清样本。通过胆道闭锁和相关疾病登记处（BARD-online.com）评估临床和随访数据。通过多重蛋白质免疫分析法评估 49 名婴儿的 25 种促炎和抗炎介质的蛋白水平，并通过 t 检验和多维主成分分析进行分析。
在 BA 患儿的肝脏中可检测到 22 种不同的免疫调节介质，而血清蛋白水平非常低或无法检测到。在 KPE 后，33 名 BA 患儿出现 RLC，需要早期进行 LTX，而 24 名患儿具有良好的疾病进程，长期保留原生肝脏（SNL）。在局部（来自肝组织样本）和全身（来自血清）免疫调节介质方面，RLC 和 SNL 之间没有显著差异。血清蛋白水平明显低于肝脏，且无统计学相关性。
我们的数据表明，局部或全身免疫调节介质不适合预测 BA 的疾病进程。因此，无法得出最佳治疗策略的结论。总的来说，我们的结论是，在 BA 中，KPE 时肝脏的炎症程度和蛋白质微环境是疾病未来进程的无关因素。
