Nedim Hadžić1, Zohreh Nademi2, Maesha Deheragoda3, Yoh Zen3, Reem Elfeky4, Austen Worth2, Paul Veys5, Giorgina Mieli-Vergani6, E Graham Davies2. 1. Pediatric Liver Center for Hepatology, Gastroenterology, and Nutrition, King's College Hospital, London, United Kingdom; Institute of Liver Studies, MowatLabs, King's College Hospital, London, United Kingdom. Electronic address: nedim.hadzic@kcl.ac.uk. 2. Immunology Department, Great Ormond Street Hospital, London, United Kingdom. 3. Institute of Liver Studies, MowatLabs, King's College Hospital, London, United Kingdom. 4. Immunology Department, Great Ormond Street Hospital, London, United Kingdom; Bone Marrow Transplant Unit, Great Ormond Street Hospital, London, United Kingdom. 5. Bone Marrow Transplant Unit, Great Ormond Street Hospital, London, United Kingdom. 6. Pediatric Liver Center for Hepatology, Gastroenterology, and Nutrition, King's College Hospital, London, United Kingdom; Institute of Liver Studies, MowatLabs, King's College Hospital, London, United Kingdom.
Abstract
OBJECTIVES: To investigate effects and outcome of hematopoietic stem cell transplantation (HSCT) on sclerosing cholangitis, in pediatric patients with different primary immunodeficiencies (PIDs). STUDY DESIGN: From databases in 2 tertiary centers for immunodeficiencies and liver disease, we have identified children with PIDs and sclerosing cholangitis, who have paired clinical, radiologic, and histologic information before and after HSCT and studied their clinical progress and outcome. RESULTS: Seven of 13 children (53.8%) died at a median interval of 4 months (range, 3 months-5 years) after HSCT. However, 6 surviving children (46.2%) with different PIDs and less severe cholangiopathies showed an improvement in markers of liver injury within months of successful unrelated reduced intensity conditioning HSCT. The repeated native liver biopsy, performed in 4 patients at a median of 96 (range, 4-144) months post-HSCT, showed a considerable improvement. Biochemical markers of liver function in the survivors completely normalized after a median of 13 months (range, 2-48). All patients continue to have a mildly dilated extrahepatic biliary system on ultrasonography with no intrahepatic ductal changes on magnetic resonance cholangiography after a follow-up of median 18 years (range, 2-20). CONCLUSIONS: Effective HSCT has the potential to improve biochemical and histologic features of cholangiopathy in children with PIDs, presumably by clearance of chronic infection following establishment of immune competence. However, careful patient selection is critical as advanced liver injury is often associated with serious complications and mortality. Crown
OBJECTIVES: To investigate effects and outcome of hematopoietic stem cell transplantation (HSCT) on sclerosing cholangitis, in pediatric patients with different primary immunodeficiencies (PIDs). STUDY DESIGN: From databases in 2 tertiary centers for immunodeficiencies and liver disease, we have identified children with PIDs and sclerosing cholangitis, who have paired clinical, radiologic, and histologic information before and after HSCT and studied their clinical progress and outcome. RESULTS: Seven of 13 children (53.8%) died at a median interval of 4 months (range, 3 months-5 years) after HSCT. However, 6 surviving children (46.2%) with different PIDs and less severe cholangiopathies showed an improvement in markers of liver injury within months of successful unrelated reduced intensity conditioning HSCT. The repeated native liver biopsy, performed in 4 patients at a median of 96 (range, 4-144) months post-HSCT, showed a considerable improvement. Biochemical markers of liver function in the survivors completely normalized after a median of 13 months (range, 2-48). All patients continue to have a mildly dilated extrahepatic biliary system on ultrasonography with no intrahepatic ductal changes on magnetic resonance cholangiography after a follow-up of median 18 years (range, 2-20). CONCLUSIONS: Effective HSCT has the potential to improve biochemical and histologic features of cholangiopathy in children with PIDs, presumably by clearance of chronic infection following establishment of immune competence. However, careful patient selection is critical as advanced liver injury is often associated with serious complications and mortality. Crown
Authors: Gil Ben Yakov; Disha Sharma; Min H Cho; Nirali N Shah; Dennis Hickstein; Amanda Urban; Dirk Darnell; Devika Kapuria; Jamie Marko; David E Kleiner; Colleen M Hadigan; Jeffrey Danielson; Hyoungjun Ham; Anusha Vittal; Helen C Su; Alexandra F Freeman; Theo Heller Journal: J Allergy Clin Immunol Pract Date: 2020-06-22
Authors: Alexis R Gibson; Adam Sateriale; Jennifer E Dumaine; Julie B Engiles; Ryan D Pardy; Jodi A Gullicksrud; Keenan M O'Dea; John G Doench; Daniel P Beiting; Christopher A Hunter; Boris Striepen Journal: PLoS Pathog Date: 2022-05-18 Impact factor: 7.464