Biliary Atresia: Clinical and Research Challenges for the Twenty-First Century.
Biliary Atresia: Clinical and Research Challenges for the Twenty-First Century.
复制标题
DOI：
10.1002/hep.29905
复制
发表时间：
2018-09
期刊：
影响因子：
--
通讯作者：
Sokol RJ
中科院分区：
文献类型：
--
作者：
Bezerra JA;Wells RG;Mack CL;Karpen SJ;Hoofnagle JH;Doo E;Sokol RJ
胆道闭锁（BA）是一种肝内外胆道系统的纤维炎症性疾病.在没有药物治疗的情况下，外科肝门肠吻合术（HPE）可以恢复胆汁引流，但在大多数儿童中，肝内疾病的进展导致门静脉高压症和晚期肝硬化的并发症。认识到如果不更好地了解疾病的根本原因和发病机制，该领域的进一步进展是不可能的，美国国立糖尿病、消化和肾脏疾病研究所赞助了一个研究讲习班，重点是创新和有前途的方法，并确定未来的研究领域。研究者讨论了使用妊娠超声的最新进展和新生儿BA筛查的结果，血清直接（结合）胆红素支持出生前发生的胆道损伤。实验和人体研究表明，环境毒素（例如，biliatresone）和病毒（例如，CMV）对胆道系统具有毒性。在宿主因素中，与胆道发育和纤毛病相关的基因中的序列变异、新生儿肝外胆管中胆管细胞糖萼和粘膜下胶原束的显著缺乏以及新生儿免疫系统的先天促炎性偏倚导致上皮损伤后对损伤和阻塞的易感性增加。这些进展为未来的研究议程奠定了基础，重点是确定导致BA的环境和宿主因素，人群筛查的潜在用途，研究年幼婴儿中显著纤维化的机制，确定疾病进展的临床替代物，以及设计针对HPE后初始引流患者亚组的临床试验。
Biliary atresia (BA) is a fibroinflammatory disease of the intra- and extrahepatic biliary tree. Without medical treatment, surgical hepatic portoenterosmy (HPE) may restore bile drainage, but progression of the intrahepatic disease results in complications of portal hypertension and advanced cirrhosis in most children. Recognizing that further progress in the field is unlikely without a better understanding of the underlying cause(s) and pathogenesis of the disease, the National Institutes of Diabetes and Digestive and Kidney Diseases sponsored a research workshop focused on innovative and promising approaches and on identifying future areas of research. Investigators discussed recent advances using gestational ultrasound and results of newborn BA screening with serum direct (conjugated) bilirubin that support a pre-natal onset of biliary injury. Experimental and human studies implicate the toxic properties of environmental toxins (e.g. biliatresone) and of viruses (e.g. CMV) to the biliary system. Among host factors, sequence variants in genes related to biliary development and ciliopathies, a notable lack of a cholangiocyte glycocalyx and of submucosal collagen bundles in the neonatal extrahepatic bile ducts, and an innate pro-inflammatory bias of the neonatal immune system contribute to an increased susceptibility to damage and obstruction following an epithelial injury. These advances form the foundation for a future research agenda focused on identifying the environmental and host factor(s) that cause BA, the potential use of population screening, studies of the mechanisms of prominent fibrosis in young infants, determinations of clinical surrogates of disease progression, and the design of clinical trials that target subgroups of patients with initial drainage following HPE.
登录
查看更多内容
DOI：
10.1002/hep.29477
发表时间：
2018-05
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Friedman SL;Ratziu V;Harrison SA;Abdelmalek MF;Aithal GP;Caballeria J;Francque S;Farrell G;Kowdley KV;Craxi A;Simon K;Fischer L;Melchor-Khan L;Vest J;Wiens BL;Vig P;Seyedkazemi S;Goodman Z;Wong VW;Loomba R;Tacke F;Sanyal A;Lefebvre E
通讯作者：
Lefebvre E
影响因子：
25.7
作者：
Baghdasaryan, Anna;Fuchs, Claudia D.;Trauner, Michael
通讯作者：
Trauner, Michael
DOI：
10.1002/cjp2.50
发表时间：
2016-07
期刊：
The journal of pathology. Clinical research
影响因子：
--
作者：
Kerola A;Lampela H;Lohi J;Heikkilä P;Mutanen A;Hagström J;Tervahartiala T;Sorsa T;Haglund C;Jalanko H;Pakarinen MP
通讯作者：
Pakarinen MP
影响因子：
120.7
作者：
Bezerra, Jorge A.;Spino, Cathie;Magee, John C.;Shneider, Benjamin L.;Rosenthal, Philip;Wang, Kasper S.;Erlichman, Jessi;Haber, Barbara;Hertel, Paula M.;Karpen, Saul J.;Kerkar, Nanda;Loomes, Kathleen M.;Molleston, Jean P.;Murray, Karen F.;Romero, Rene;Schwarz, Kathleen B.;Shepherd, Ross;Suchy, Frederick J.;Turmelle, Yumirle P.;Whitington, Peter F.;Moore, Jeffrey;Sherker, Averell H.;Robuck, Patricia R.;Sokol, Ronald J.
通讯作者：
Sokol, Ronald J.
影响因子：
5.1
作者：
de Vries, Willemien;de Langen, Zacharias J.;Verkade, Henkjan J.
通讯作者：
Verkade, Henkjan J.