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Longitudinal GGT Trajectories Identify Prognostic Phenotypes in Paediatric Primary Sclerosing Cholangitis
Daniela Denier1, Yiming Emmett Peng2, Mansi Amin3
1Division of Paediatric Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Switzerland.
JHEP Reports : Innovation in Hepatology
|June 26, 2026
Summary
Gamma-glutamyl transferase (GGT) trajectories identify distinct pediatric primary sclerosing cholangitis (PSC) patient groups. Early GGT normalization, not just baseline levels, predicts better transplant-free survival in PSC.
Area of Science:
- Pediatric gastroenterology and hepatology
- Biomarker trajectory analysis
- Clinical heterogeneity in rare diseases
Background:
- Primary sclerosing cholangitis (PSC) exhibits significant clinical variability in children.
- Current prognostic assessments rely on single timepoint biomarker measurements, missing dynamic changes.
- Gamma-glutamyl transferase (GGT) levels at one year are known indicators of favorable outcomes.
Purpose of the Study:
- To identify distinct GGT trajectory phenotypes in pediatric PSC using latent class mixed modeling.
- To evaluate the prognostic significance of these identified GGT trajectory clusters.
- To determine if early biochemical response predicts long-term transplant-free survival in pediatric PSC.
Main Methods:
- Analysis of 782 children with PSC from the Pediatric PSC Consortium with longitudinal GGT data.
- Application of latent class mixed models to log-transformed GGT values.
- Assessment of associations between trajectory clusters and transplant-free survival using Cox proportional hazards models.
Main Results:
- Four distinct GGT trajectory clusters were identified: persistently elevated (23%), moderate-stable (30%), elevated-declining (26%), and persistently low (21%).
- Significant differences in 5-year transplant-free survival were observed across clusters (74% to 96%, p<0.0001).
- The elevated-declining cluster normalized GGT by year one and had favorable outcomes, similar to the persistently low cluster.
Conclusions:
- GGT trajectory phenotypes define clinically meaningful subgroups within pediatric PSC, each with a distinct prognosis.
- Early normalization of GGT, observed in the elevated-declining cluster, is a strong predictor of favorable long-term outcomes.
- Trajectory-based phenotyping, predictable with early GGT values, offers a valuable tool for risk stratification and clinical trial design in pediatric PSC.