Prediction, identification and progression of histopathological liver disease activity in children with intestinal
Annika Mutanen1, Jouko Lohi2, Laura Merras-Salmio3
1Department of Pediatric Surgery, Pediatric Liver and Gut Research Group, Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Insights
Intestinal failure-associated liver disease (IFALD) in children can be predicted by parenteral nutrition (PN) dependency and intestinal disruption. Non-invasive markers like GGT, citrulline, and liver stiffness accurately detect IFALD, enabling better monitoring and liver protection.
Area of Science:
- Pediatric Gastroenterology
- Hepatology
- Clinical Nutrition
Background:
- Intestinal failure-associated liver disease (IFALD) poses a significant risk in children requiring parenteral nutrition (PN).
- Diagnostic criteria, progression, and monitoring for IFALD remain undefined, necessitating further research.
Purpose of the Study:
- To assess predictors, non-invasive markers, and progression of histopathological liver disease in pediatric patients with intestinal failure (IF).
- To identify reliable methods for diagnosing and monitoring IFALD without invasive liver biopsies.
Main Methods:
- 77 children with IF underwent diagnostic liver biopsy, with 48 having follow-up biopsies.
- Evaluated liver biochemistry, liver stiffness, serum citrulline, spleen size, esophageal varices, and clinical data.
- Classified IFALD into active, chronic, or no IFALD based on histopathology.
Main Results:
- Active IFALD was associated with low serum citrulline, PN dependency, and younger age.
- Most patients showed normalized or improved liver histopathology, but 19% retained active IFALD and 6.3% progressed.
- Gamma-glutamyltransferase (GGT), citrulline, and liver stiffness accurately identified active IFALD (AUROC > 0.90).
Conclusions:
- Intestinal disruption and PN dependency predict active IFALD.
- Non-invasive markers (GGT, citrulline, liver stiffness) offer accurate detection and monitoring of IFALD.
- These findings pave the way for improved monitoring and targeted liver protection strategies in IF patients.
Background & Aims:
Diagnostic criteria, progression risk and optimal monitoring for intestinal failure (IF)-associated liver disease (IFALD) remain undefined. We assessed predictors, non-invasive markers and progression of histopathological liver disease in patients with IF.
Methods:
In total, 77 children with IF and median age of 1.7 years underwent diagnostic liver biopsy, which was repeated in 48 patients after 2.9 years with simultaneous evaluation of liver biochemistry, liver stiffness, serum citrulline (a surrogate for viable enterocyte mass), spleen size, esophageal varices and clinical data. Patients were staged according to histopathological liver disease activity: active IFALD (cholestasis and/or inflammation), chronic IFALD (significant fibrosis and/or steatosis), or no IFALD (none of these features).
Results:
Diagnostic liver biopsy revealed active, chronic or no IFALD in 48%, 21% and 31% of patients. Active IFALD was segregated by low serum citrulline, parenteral nutrition (PN) dependency and young age, while weaning off PN and older age predicted chronic IFALD. Although the liver histopathology in most patients either normalized (52%) or transformed to a less reactive (chronic) disease stage (23%), 19% of patients retained and 6.3% progressed to an active cholestatic/inflammatory IFALD phenotype. Decreased serum citrulline and PN-dependency also predicted active IFALD in follow-up biopsies. Increased median liver biochemistry values and liver stiffness only associated with active IFALD, which was accurately identified by gamma-glutamyltransferase (GGT), citrulline and liver stiffness, their combinations reaching diagnostic and follow-up AUROC values above 0.90.
Conclusions:
Active IFALD, essentially predicted by intestinal disruption and PN-dependency, was accurately detected by GGT, liver stiffness and citrulline, which together with recent advances in clinical management options, provides new avenues for monitoring and targeted liver protection in patients with IF.
Lay Summary:
Liver disease is a common and critical complication in patients with intestinal failure, who require intravenous nutrition for survival due to severe intestinal dysfunction. We showed that both intravenous nutrition dependency and intestinal disruption essentially predicted development of active histopathological liver disease, which persisted in 25% of patients during long-term follow-up and could be accurately detected without the need for liver biopsy. Identification of the active and potentially progressive histopathology offers new possibilities for monitoring and targeted liver protection in patients with intestinal failure.
