Abstract
Background and Aims: Liver fibrosis is common in children with NAFLD and is an important determinant of outcomes. High-performing noninvasive models to assess fibrosis in children are needed. The objectives of this study were to evaluate the performance of existing pediatric and adult fibrosis prediction models and to develop a clinical prediction rule for identifying moderate-to-severe fibrosis in children with NAFLD. Approach and Results: We enrolled children with biopsy-proven NAFLD in the Nonalcoholic Steatohepatitis Clinical Research Network within 90 days of liver biopsy. We staged liver fibrosis in consensus using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. We evaluated existing pediatric and adult models for fibrosis and developed a new pediatric model using the least absolute shrinkage and selection operator with linear and spline terms for discriminating moderate-to-severe fibrosis from none or mild fibrosis. The model was internally validated with 10-fold cross-validation. We evaluated 1055 children with NAFLD, of whom 26% had moderate-to-severe fibrosis. Existing models performed poorly in classifying fibrosis in children, with area under the receiver operator curves (AUC) ranging from 0.57 to 0.64. In contrast, our new model, fibrosis in pediatric NAFLD was derived from fourteen common clinical variables and had an AUC of 0.79 (95% CI: 0.77-0.81) with 72% sensitivity and 76% specificity for identifying moderate-to-severe fibrosis. Conclusion: Existing fibrosis prediction models have limited clinical utility in children with NAFLD. Fibrosis in pediatric NAFLD offers improved performance characteristics for risk stratification by identifying moderate-to-severe fibrosis in children with NAFLD.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1381-1392 |
| Number of pages | 12 |
| Journal | Hepatology |
| Volume | 79 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2024 |
Funding
Stavra A. Xanthakos received grants from Target. Miriam B. Vos consults for Albireo, Boehringer Ingelheim, Eli Lilly, and Intercept. She received grants from LabCorp, Quest, Sonic Incytes, and Target. She owns stock in Thiogenesis and Tern. Jean P. Molleston received grants from AbbVie, Albireo, CF Foundation, Gilead, and Mirium. Ajay K. Jain advises and received grants from Mirium. He consults for Camp4. The remaining authors have no conflicts to report. The authors thank the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) for its support of the NASH CRN and this research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. TONIC: The TONIC trial was conducted by the NASH CRN and supported in part by the Intramural Research Program of the National Cancer Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The vitamin E and matching placebo were provided by Pharmavite through a Clinical Trial Agreement with the NIH. CyNCh: The CyNCh trial was conducted by the NASH CRN and supported in part by the Intramural Research Program of the National Cancer Institute and by a Collaborative Research and Development Agreement (CRADA) between NIDDK and Raptor Pharmaceuticals. ClinicalTrials.gov numbers NAFLD Pediatric Database 2: NCT01061684 TONIC: NCT00063635 CyNCh: NCT01529268 The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (grants U01DK061713, U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U24DK061730). Additional support was received from the National Center for Advancing Translational Sciences (NCATS) (grants UL1TR000077, UL1TR000150, UL1TR000424, UL1TR000006, UL1TR000448, UL1TR000040, UL1TR000100, UL1TR000004, UL1TR000423, UL1TR000454). The content and opinions expressed in this article are the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. The CyNCh trial was conducted by the NASH CRN and supported in part by the Intramural Research Program of the National Cancer Institute and by a Collaborative Research and Development Agreement (CRADA) between NIDDK and Raptor Pharmaceuticals.
ASJC Scopus subject areas
- Hepatology