Diagnosis of Primary Sclerosing Cholangitis Beyond Childhood is Associated with Worse Outcomes

Stefani Tica; Saad Alghamdi; Christopher Tait; Bonsa Nemera; Yumirle Turmelle; Jaquelyn Fleckenstein; Janis Stoll; Sakil Kulkarni

doi:10.1016/j.jceh.2021.03.006

Diagnosis of Primary Sclerosing Cholangitis Beyond Childhood is Associated with Worse Outcomes

J Clin Exp Hepatol. 2022 Jan-Feb;12(1):110-117. doi: 10.1016/j.jceh.2021.03.006. Epub 2021 Mar 26.

Authors

Stefani Tica¹, Saad Alghamdi², Christopher Tait², Bonsa Nemera¹, Yumirle Turmelle^{1

2}, Jaquelyn Fleckenstein², Janis Stoll¹, Sakil Kulkarni¹

Affiliations

¹ Department of Pediatrics, Washington University in St. Louis, St. Louis Children's Hospital, St. Louis, MO, USA.
² Department of Internal Medicine, Washington University in St. Louis, Barnes Jewish Hospital, St. Louis, MO, USA.

Abstract

Background: The elucidation of differences between adult and pediatric-onset primary sclerosing cholangitis (PSC) may inform clinical decision making, and whether results of adult PSC clinical trials can be extrapolated to pediatric subjects.

Methods: A single-center retrospective analysis of PSC subjects diagnosed during the epoch 2000-13 was conducted. Demographic, clinical, and laboratory data were compared between PSC subjects diagnosed between 0-18 (pediatric) and 19+ (adult) years of age. An adverse outcome was defined as PSC-related death, liver transplant, or malignancy. Survival without any of these was defined as event-free survival.

Results: Analyses of 28 pediatric-diagnosed and 59 adult-diagnosed subjects revealed that incidence of early portal hypertension (PHT; P = 0.2), laboratory parameters of liver disease severity, and fibrosis grade at diagnosis were comparable between adult and pediatric PSC subjects. Adult-diagnosed PSC subjects had higher incidences of adverse outcomes compared to pediatric-diagnosed PSC subjects (P = 0.02). The age group 0-18 years (n = 30) had significantly better event-free survival compared to the age group more than 40 years (n = 25; P = 0.03). The prevalence of PHT in adult PSC subjects was 2.6 that of pediatric PSC subjects. PHT adversely affected outcomes in both adult (P < 0.001) and pediatric (P = 0.01) subjects. Adult PSC subjects were more likely to develop biliary complications (BCs; P = 0.001), ascites (P = 0.004), and variceal bleed (P = 0.03). Adult PSC subjects were more likely to have extra-hepatic co-morbidities (P < 0.001). Adult subjects had a longer follow-up duration compared to pediatric subjects (P = 0.06).

Conclusion: Despite having a comparable clinical, laboratory, and histologic biomarkers of liver disease severity at the time of diagnosis, adult PSC subjects had a worse outcome compared to pediatric PSC subjects. Possible reasons for this finding include higher incidence of PHT, BCs, extra-hepatic co-morbidities, and longer duration of follow-up.

Keywords: AIH, autoimmune hepatitis; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ERCP, endoscopic cholangiopancreatography; GGT, gamma-glutamyl transferase; GI, gastrointestinal; IBD, inflammatory bowel disease; INR, international normalized ratio; MR imaging, magnetic resonance imaging; MRCP, magnetic resonance cholangiopancreatography; PHT, portal hypertension; PSC, primary sclerosing cholangitis; age; cholangitis; outcome; primary; sclerosing; x ULN, times upper limit of normal.