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Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis: Predictors of Gamma Glutamyltransferase
Mark Deneau1, Emily Perito2, Amanda Ricciuto3
1Department of Pediatrics, University of Utah, Salt Lake City, UT.
Insights
Gamma glutamyltransferase (GGT) normalization occurred in 46% of children with primary sclerosing cholangitis treated with ursodeoxycholic acid (UDCA). Achieving GGT normalization predicted better long-term outcomes, suggesting UDCA benefits this subgroup.
Area of Science:
- Pediatric Gastroenterology
- Hepatology
- Clinical Pharmacology
Background:
- Primary sclerosing cholangitis (PSC) is a chronic liver disease affecting children, often requiring long-term management.
- Ursodeoxycholic acid (UDCA) is a common therapy for pediatric PSC, but predictors of treatment response are not fully understood.
- Gamma glutamyltransferase (GGT) is a key biomarker in cholestatic liver diseases, and its normalization is a treatment goal.
Purpose of the Study:
- To identify patient factors associated with normalization of gamma glutamyltransferase (GGT) levels in children with primary sclerosing cholangitis (PSC) treated with ursodeoxycholic acid (UDCA).
- To evaluate the impact of GGT normalization on long-term outcomes in pediatric PSC patients receiving UDCA.
Main Methods:
- Retrospective analysis of patient records from 46 centers.
- Inclusion criteria: pediatric PSC patients with baseline GGT ≥50 IU/L, initiating UDCA within 1 month of diagnosis, and continuing therapy for ≥1 year.
- GGT normalization defined as GGT <50 IU/L without major adverse events in the first year.
Main Results:
- Of 263 patients, 46% achieved GGT normalization within the first year of UDCA therapy.
- Factors associated with normalization included lower prevalence of Crohn's disease, lower total bilirubin, lower AST-to-Platelet Ratio Index (APRI), higher platelet count, and higher serum albumin at diagnosis.
- Patients achieving GGT normalization demonstrated significantly better 5-year native liver survival (99%) compared to those who did not (77%).
Conclusions:
- Less than half of pediatric PSC patients achieve GGT normalization with UDCA therapy within the first year.
- GGT normalization is linked to favorable long-term outcomes, suggesting a clinically meaningful response.
- Patients with Crohn's disease or markers of advanced fibrosis are less likely to normalize GGT, potentially indicating a need for alternative therapies.
Objective:
To investigate patient factors predictive of gamma glutamyltransferase (GGT) normalization following ursodeoxycholic acid (UDCA) therapy in children with primary sclerosing cholangitis.
Study Design:
We retrospectively reviewed patient records at 46 centers. We included patients with a baseline serum GGT level ≥50 IU/L at diagnosis of primary sclerosing cholangitis who initiated UDCA therapy within 1 month and continued therapy for at least 1 year. We defined "normalization" as a GGT level <50 IU/L without experiencing portal hypertensive or dominant stricture events, liver transplantation, or death during the first year.
Results:
We identified 263 patients, median age 12.1 years at diagnosis, treated with UDCA at a median dose of 15 mg/kg/d. Normalization occurred in 46%. Patients with normalization had a lower prevalence of Crohn's disease, lower total bilirubin level, lower aspartate aminotransferase to platelet ratio index, greater platelet count, and greater serum albumin level at diagnosis. The 5-year survival with native liver was 99% in those patients who achieved normalization vs 77% in those who did not.
Conclusions:
Less than one-half of the patients treated with UDCA have a complete GGT normalization in the first year after diagnosis, but this subset of patients has a favorable 5-year outcome. Normalization is less likely in patients with a Crohn's disease phenotype or a laboratory profile suggestive of more advanced hepatobiliary fibrosis. Patients who do not achieve normalization could reasonably stop UDCA, as they are likely not receiving clinical benefit. Alternative treatments with improved efficacy are needed, particularly for patients with already-advanced disease.
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