TY - JOUR
T1 - The natural history of primary sclerosing cholangitis in 781 children
T2 - A multicenter, international collaboration
AU - Deneau, Mark R.
AU - El-Matary, Wael
AU - Valentino, Pamela L.
AU - Abdou, Reham
AU - Alqoaer, Khaled
AU - Amin, Mansi
AU - Amir, Achiya Z.
AU - Auth, Marcus
AU - Bazerbachi, Fateh
AU - Broderick, Annemarie
AU - Chan, Albert
AU - Cotter, Jillian
AU - Doan, Sylvia
AU - El-Youssef, Mounif
AU - Ferrari, Federica
AU - Furuya, Katryn N.
AU - Gottrand, Madeleine
AU - Gottrand, Frederic
AU - Gupta, Nitika
AU - Homan, Matjaz
AU - Kamath, Binita M.
AU - Kim, Kyung Mo
AU - Kolho, Kaija Leena
AU - Konidari, Anastasia
AU - Koot, Bart
AU - Iorio, Raffaele
AU - Ledder, Oren
AU - Mack, Cara
AU - Martinez, Mercedes
AU - Miloh, Tamir
AU - Mohan, Parvathi
AU - O'Cathain, Niamh
AU - Papadopoulou, Alexandra
AU - Ricciuto, Amanda
AU - Saubermann, Lawrence
AU - Sathya, Pushpa
AU - Shteyer, Eyal
AU - Smolka, Vratislav
AU - Tanaka, Atushi
AU - Varier, Raghu
AU - Venkat, Veena
AU - Vitola, Bernadette
AU - Vos, Miriam B.
AU - Woynarowski, Marek
AU - Yap, Jason
AU - Jensen, M. Kyle
N1 - Publisher Copyright:
© 2017 by the American Association for the Study of Liver Diseases.
PY - 2017/8
Y1 - 2017/8
N2 - There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC–inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. Conclusion: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC–inflammatory bowel disease are more favorable disease phenotypes. (Hepatology 2017;66:518–527).
AB - There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC–inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. Conclusion: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC–inflammatory bowel disease are more favorable disease phenotypes. (Hepatology 2017;66:518–527).
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U2 - 10.1002/hep.29204
DO - 10.1002/hep.29204
M3 - Article
C2 - 28390159
AN - SCOPUS:85021369385
SN - 0270-9139
VL - 66
SP - 518
EP - 527
JO - Hepatology
JF - Hepatology
IS - 2
ER -