Clinical Center for Cholestatic Liver Disease in Children

儿童胆汁淤积性肝病临床中心

• 批准号: 10631943
• 负责人: Alexander Miethke
• 金额: $ 80.1万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10631943
• 关键词: Acetylcysteine; Acute; Alagille Syndrome; Ancillary Study; Antioxidants; Bile Acids; Biliary; Biliary Atresia; Biological Markers; Caring; Child; Child Care; Childhood; Cholestasis; Clinical; Clinical Data; Clinical Research; Clinical Research Protocols; Clinical Trials; Collection; Cystic Fibrosis; Data; Data Analyses; Data Coordinating Center; Defect; Development; Disease; Disease Outcome; Drainage procedure; Education; Enrollment; Epithelium; Etiology; Funding; Genetic; Goals; Grant; IL8 gene; Infant; Infrastructure; Injury; Institutional Review Boards; Intervention; Intestines; Intravenous Immunoglobulins; Knowledge; Leadership; Liver; Liver Fibrosis; Liver diseases; Logic; Longitudinal Studies; Magnetic Resonance Imaging; Maintenance; Matrilysin; Measures; Mitochondria; Molecular; National Institute of Diabetes and Digestive and Kidney Diseases; Neonatal; Observational Study; Outcome; Paper; Pathogenesis; Pathology; Patients; Performance; Portal Hypertension; Positioning Attribute; Progressive intrahepatic cholestasis; Prospective Studies; Protocols documentation; Pruritus; Publications; Quality of life; RNA purification; Radiology Specialty; Reporting; Research; Research Infrastructure; Research Personnel; Role; Safety; Serum; Services; Sodium; Steroids; Tissue Sample; Tissues; Translational Research; U-Series Cooperative Agreements; United States National Institutes of Health; Vancomycin; Work; alpha 1-Antitrypsin Deficiency; bile acid transporter; chronic liver disease; clinical center; clinical development; clinical research site; clinical translation; clinical trial protocol; data submission; design; disease natural history; efficacy evaluation; elastography; improved; improved outcome; innovation; intrahepatic; liver cystic fibrosis; liver stiffness; member; open label; primary sclerosing cholangitis; prospective; protocol development; response; small molecule inhibitor; support network; symposium; translational study

PROJECT SUMMARY/ABSTRACT We propose to remain a Member of the Childhood Liver Disease Research Network (ChiLDReN). As a Charter Member of the Network, our proposal represents a logical extension of the long-standing commitment of our Center to improve the care of children with chronic liver disease through innovative patient-based research. In the previous member of the Network, we worked collaboratively with investigators from other Centers and with the Data Coordinating Center to build a strong infrastructure to conduct patient-based studies on biliary atresia, cholestatic syndromes, mitochondrial hepatopathies and cystic fibrosis, with initial work to develop an observational and interventional protocol for children with primary sclerosing cholangitis (PSC). Our key contributions in the previous cycle included: 1) leadership and/or partnership in the development of network-wide clinical studies, with data analyses and publication of 11 original papers; 2) completion of the first two clinical trials (the steroid trial START and the IV-IG trial PRIME); 3) high enrollment and retention of subjects into prospective studies, including the new FORCE study; 4) timely processing of liver tissue by the staff of RNA Purification Service, Bile Acid Analysis Service, and Pathology Service to support Network studies; and 5) co-leading the organization of an NIH symposium on biliary atresia, with publication of its proceedings. We look forward to significantly contributing to the scientific goals and operational excellence of ChiLDReN through three aims. In Aim 1, we will enroll subjects into prospective ChiLDReN protocols to enable observational studies and translational science. This will be done by pursuing high enrollment rate of subjects into approved protocols, with the timely collection and submission of data and tissue samples to meet the enrollment goals established by the Network. In Aim 2, we will develop and implement research protocols for clinical trials. We are working with Network investigators to conduct a trial to determine the efficacy and safety of a small molecule inhibitor of the intestinal sodium-dependent bile acid transporter (IMAGINE-II trial) in children with cholestasis-associated pruritus. We are also developing a clinical trial to determine the efficacy of Vancomycin in children with PSC. And in Aim 3, we propose a new clinical trial focusing on the use of anti- oxidants to decrease biliary injury in infants who acquire biliary drainage after hepatoportoenterostomy for biliary atresia. We also propose an ancillary study to determine the role of matrix metalloproteinase-7 as a biomarker of hepatic fibrosis in biliary atresia. By pursuing the three aims, we will be well positioned to fully execute the new Network aims of pursuing translational science projects and conducting trials to improve the outcome of children with cholestatic liver diseases.

项目总结/文摘

项目成果

Large-scale proteomics identifies MMP-7 as a sentinel of epithelial injury and of biliary atresia.

• DOI: 10.1126/scitranslmed.aan8462
• 发表时间: 2017-11-22
• 期刊: Science translational medicine
• 影响因子: 17.1
• 作者: Lertudomphonwanit C;Mourya R;Fei L;Zhang Y;Gutta S;Yang L;Bove KE;Shivakumar P;Bezerra JA
• 通讯作者: Bezerra JA

Exome Sequencing in Individuals with Isolated Biliary Atresia.

孤立性胆道闭锁个体的外显子组测序。

• DOI: 10.1038/s41598-020-59379-4
• 发表时间: 2020
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Rajagopalan,Ramakrishnan;Tsai,EllenA;Grochowski,ChristopherM;Kelly,SusanM;Loomes,KathleenM;Spinner,NancyB;Devoto,Marcella
• 通讯作者: Devoto,Marcella

Treatment of bile acid amidation defects with glycocholic acid.

• DOI: 10.1002/hep.27401
• 发表时间: 2015-01
• 期刊: HEPATOLOGY
• 影响因子: 13.5
• 作者: Heubi, James E.;Setchell, Kenneth D. R.;Jha, Pinky;Buckley, Donna;Zhang, Wujuan;Rosenthal, Philip;Potter, Carol;Horslen, Simon;Suskind, David
• 通讯作者: Suskind, David

Dendritic cells regulate natural killer cell activation and epithelial injury in experimental biliary atresia.

• DOI: 10.1126/scitranslmed.3002069
• 发表时间: 2011-09-28
• 期刊: Science translational medicine
• 影响因子: 17.1
• 作者: Saxena V;Shivakumar P;Sabla G;Mourya R;Chougnet C;Bezerra JA
• 通讯作者: Bezerra JA

Biliary atresia: will blocking inflammation tame the disease?

• DOI: 10.1146/annurev-med-042909-093734
• 发表时间: 2011
• 期刊: Annual review of medicine
• 影响因子: 10.5
• 作者: Bessho K;Bezerra JA
• 通讯作者: Bezerra JA