Gamma-glutamyltransferase testing in paediatric inflammatory bowel disease to screen for primary sclerosing
Besrat Berhane1,2, Wouter Sjoerd van de Put1,2, Patrick Ferry van Rheenen3,2
1Department of Paediatric Gastroenterology and Hepatology, Beatrix Children's Hospital, University Medical Centre Groningen, Groningen, The Netherlands.
Insights
In children with inflammatory bowel disease (IBD), a gamma-glutamyltransferase (GGT) level below 2 times the upper limit of normal (ULN) indicates a very low risk of primary sclerosing cholangitis (PSC). This finding helps avoid unnecessary invasive tests for pediatric IBD patients.
Area of Science:
- Pediatric Gastroenterology
- Hepatology
- Inflammatory Bowel Disease Research
Background:
- Elevated liver enzymes, specifically gamma-glutamyltransferase (GGT), are common in children with inflammatory bowel disease (IBD).
- Primary sclerosing cholangitis (PSC) is a serious complication that can occur in children with IBD, necessitating accurate diagnostic approaches.
- Determining the optimal GGT threshold is crucial for distinguishing IBD patients with and without PSC, thereby guiding clinical management.
Purpose of the Study:
- To identify the most effective gamma-glutamyltransferase (GGT) threshold for differentiating primary sclerosing cholangitis (PSC) in pediatric patients with inflammatory bowel disease (IBD) and elevated liver enzymes.
- To evaluate the diagnostic performance of different GGT thresholds in identifying PSC among children with IBD.
Main Methods:
- A delayed-type diagnostic study with a paired design was conducted, involving regular GGT screening in children with IBD.
- Primary sclerosing cholangitis (PSC) diagnosis was confirmed using magnetic resonance cholangiopancreatography (MRCP) and/or liver histology.
- The study assessed the negative predictive value (NPV) of GGT thresholds at 1×, 2×, and 5× the upper limit of normal (ULN), alongside receiver operating characteristic (ROC) analysis for an optimal threshold.
Main Results:
- Out of 469 children with IBD, 132 (28.1%) had elevated GGT levels, and 34 (7.2%) were diagnosed with PSC.
- A GGT threshold of 2× ULN (approximately 100 U/L) demonstrated the best test characteristics, achieving an NPV of 98% and a negative likelihood ratio of 0.04.
- The optimal GGT threshold identified via ROC analysis was 103.5 U/L, with an area under the curve of 0.83, indicating good diagnostic accuracy.
Conclusions:
- In pediatric patients with IBD, a GGT level below 2× ULN suggests an extremely low likelihood of PSC, potentially obviating the need for MRCP and liver biopsy.
- Regular GGT monitoring is recommended for children with IBD, as PSC can develop over time even with initially normal or mildly elevated GGT levels.
- This study provides a valuable GGT threshold to refine diagnostic strategies for PSC in pediatric IBD populations, improving patient care and reducing unnecessary procedures.
Objective:
To investigate, among children with inflammatory bowel disease (IBD) and elevated liver enzymes, what threshold of gamma-glutamyltransferase (GGT) best distinguishes those with and without primary sclerosing cholangitis (PSC).
Method:
Delayed-type diagnostic study with a paired design. Children with IBD were regularly screened with GGT (index test). Confirmation of PSC was based on magnetic resonance cholangiopancreatography (MRCP) and/or liver histology (preferred reference standard). Children at low risk of PSC continued regular GGT testing for latent PSC to become visible (alternative reference test). The primary outcome was the negative predictive value (NPV) using three predefined test thresholds, respectively, 1, 2 and 5× the upper limit of normal (ULN). The secondary outcome was the GGT threshold based on receiver operating characteristic analysis.
Results:
132 of 469 children (28.1%) had elevated GGT levels at their first colonoscopy or during follow-up. Eventually, 34 children (7.2%) were diagnosed with PSC. Median GGT (IQR) for children with and without PSC was 227 (127-345) and 77 (59-138) U/L, respectively. Of the predefined GGT thresholds, 2× ULN (ie, 100 U/L) had the best test characteristics, including an NPV of 98% and a negative likelihood ratio of 0.04 (95% CI 0.01 to 0.31). The area under the curve was 0.83 (95% CI: 0.75 to 0.90) and the optimal GGT threshold was 103.5 U/L.
Conclusion:
In children with IBD who have GGT elevations less than 2× ULN, the likelihood of PSC is extremely low. In such cases, MRCP and liver biopsy can be omitted. Regular GGT monitoring is advised, as PSC may develop over time.
