Disease progression in paediatric‐ and adult‐onset sclerosing cholangitis: Results from two independent Dutch registries

Abstract

Background & Aims Sclerosing cholangitis (SC) is a severe liver disease leading to destruction of bile ducts. It is believed to run a milder course in children than in adults. To test this assumption, we evaluated time‐to‐complication curves in two independent paediatric‐onset cohorts from the same geographical area. Methods Short‐term disease outcomes were evaluated with an online clinical registry that was filled with data on children with SC diagnosed between 2000 and 2017 and who were followed bi‐annually thereafter. Long‐term disease outcomes were evaluated in a paediatric‐onset subcohort derived from a previously published population‐based study from the Netherlands. Time‐to‐complication in the first cohort was defined as the time from diagnosis until portal hypertension, biliary obstructions and infections, development of malignancy, or liver transplantation, whichever came first. In the second cohort time‐to‐complication was defined as the time until liver transplantation or PSC‐related death. Results Median age at diagnosis in the first cohort (n = 86) was 12.3 years. In the first 5 years post‐diagnosis 23% of patients developed complications. The patients in the population‐based study (n = 683) were stratified into those diagnosed before the age of 18 years (‘paediatric‐onset’ subcohort, n = 43) and those diagnosed after the age of 18 years (‘adult‐onset’ subcohort, n = 640). Median age at diagnosis was 14.6 and 40.2 years, respectively. Median time‐to‐complication in the paediatric‐onset and adult‐onset subcohorts was not statistically different. Conclusion Paediatric and adult‐onset SC run a similar long‐term disease course. Paediatricians who treat children with SC should monitor them closely to recognize early complications and control long‐term sequelae.

Gamma‐glutamyl transferase and disease course in pediatric‐onset primary sclerosing cholangitis: A single‐center cohort study

“…The Ethical Review Board of the Erasmus MC in Rotterdam, who assessed the initial study protocol on pediatric PSC patients conducted by Joose et al, 5 waived the need for informed consent due to the anonymous and noninterventional fashion of the study. For the present study, we obtained secondary approval from the Ethical Review Board of the UMCG.…”

“…The diagnosis of PSC was based on the biochemical profile (elevation of GGT, elevated conjugated bilirubin levels, or both) with either bile duct irregularities on imaging (MRCP or endoscopic retrograde cholangiopancreatography [ERCP]) or abnormal liver histology characteristic for PSC. 3 , 5 The presence of bile duct irregularities on cholangiography classified patients as having large duct PSC, whereas a normal cholangiogram in combination with histopathological findings supporting PSC classified patients as having small duct PSC. Patients who did not undergo cholangiography and liver histology at the time of diagnosis were excluded from analysis.…”

“…Patients who did not undergo cholangiography and liver histology at the time of diagnosis were excluded from analysis. Co‐occurrence of AIH was diagnosed in case of simultaneously increased levels of transaminases and immunoglobulin G, and/or the presence of autoantibodies (including antismooth muscle, antiliver cytosol, antiliver kidney microsome type 1, or antinuclear antibodies 5 . We excluded patients with a baseline GGT <50 U/L as well as patients with missing baseline GGT or GGT results at 1 year after diagnosis.…”

“… 3 , 4 Patients with fibrosing cholangiopathy on histology, but without cholangiographic abnormalities, are usually classified as having “small duct disease.” PSC can coexist with autoimmune hepatitis (AIH), which is more frequently recognized in children compared with adults (33% vs. 7%). 5 , 6 This condition has been described as overlap syndrome based on the frequent concurrence of increased levels of autoantibodies, transaminases, and hypergammaglobulinemia. 5 These patients usually respond to steroids, at least biochemically.…”

“… 5 , 6 This condition has been described as overlap syndrome based on the frequent concurrence of increased levels of autoantibodies, transaminases, and hypergammaglobulinemia. 5 These patients usually respond to steroids, at least biochemically. 7 PSC has a strong association with inflammatory bowel disease (IBD).…”