CHILDREN with paediatric primary sclerosing cholangitis (PSC) could be stratified into distinct risk groups using changes in gamma-glutamyl transferase (GGT) during the first six months after diagnosis, according to a study of 782 patients.
The findings suggest that early biochemical response, rather than baseline GGT alone, COULD provide a more reliable indicator of long-term transplant-free survival.
PSC is a chronic cholestatic liver disease in which progressive inflammation and scarring of the bile ducts can lead to cirrhosis, liver failure and cholangiocarcinoma. The condition follows a highly variable clinical course, making it difficult to identify which children are most likely to experience disease progression.
GGT Trajectories Reveal Distinct Paediatric PSC Outcomes
Researchers analysed serial GGT measurements from 782 children enrolled in the Paediatric PSC Consortium who had a baseline result and at least one additional measurement during three years of follow-up. Using latent class mixed modelling, they identified four GGT trajectory phenotypes: persistently elevated (23%), moderate-stable (30%), elevated-declining (26%) and persistently low (21%).
Five-year transplant-free survival differed significantly across the four trajectory groups (p<0.0001), ranging from 74% in the persistently elevated cluster to 98% in the elevated-declining cluster. Children with persistently low GGT had a 96% transplant-free survival rate, while those in the moderate-stable group achieved 86%.
Notably, patients with elevated GGT at baseline who experienced normalisation by one year had transplant-free survival comparable with those whose GGT remained consistently low, despite similar starting values.
Early Biochemical Response May Support Risk Stratification
After adjustment for baseline characteristics, children in the persistently elevated and moderate-stable groups had significantly greater transplant hazards than those with persistently low GGT (HR 6.45 and HR 3.00, respectively). By contrast, outcomes for the elevated-declining group did not differ significantly from the persistently low cluster.
The investigators also found that trajectory membership could be predicted using baseline and six-month GGT values, achieving an area under the curve of 0.83. This suggests repeated early GGT measurements could help clinicians identify higher-risk patients sooner than relying on a single assessment.
Potential Implications for Clinical Care and Research
Baseline characteristics also differed between trajectory groups. Less favourable phenotypes tended to include older children, more boys, greater large duct involvement, lower albumin and higher liver enzyme concentrations. More favourable trajectories were linked with younger age, higher platelet counts and albumin, and a greater prevalence of inflammatory bowel disease.
The authors suggest trajectory-based phenotyping could improve prognostic assessment in paediatric PSC and support clinical trial design through patient enrichment strategies and potential early surrogate endpoints. They add that monitoring changes in GGT over time captures clinically meaningful differences that single timepoint biomarker measurements may overlook.
Reference
Denier D et al. Longitudinal GGT trajectories identify prognostic phenotypes in paediatric primary sclerosing cholangitis. JHEP Rep. 2026;DOI:10.1016/j.jhepr.2026.101940.
Featured image: Molekuul.be on Adobe Stock
- Author:
