Performance of ELF Serum Markers in Predicting Fibrosis Stage in Pediatric Non-Alcoholic Fatty Liver Disease

Background & Aims

Nonalcoholic fatty liver disease (NAFLD) is the most frequent chronic liver disease in children and adolescents in industrialized countries. It is important to accurately determine the stage of fibrosis in these patients. The enhanced liver fibrosis (ELF) test has been validated for staging liver fibrosis in adult patients with chronic liver diseases, including NAFLD. We investigated the performance of this test in assessing liver fibrosis in children and adolescents with NAFLD, identified by biopsy.

Methods

The ELF test was performed on a panel of serum samples collected from 112 consecutive subjects that were likely to have NAFLD (64 male, mean age of 13.8 ± 3.3). A previously described and validated algorithm was used to analyze the data on hyaluronic acid (HA), amino-terminal propeptide of type III collagen (PIIINP), and tissue inhibitor of metalloproteinase 1 (TIMP-1) levels.

Results

In pediatric patients with NAFLD, the ELF test predicted liver fibrosis stage with a high degree of sensitivity and specificity; results were superior to those reported for adults. The area under receiver operating characteristic curves/best possible ELF test cut-off values for the prediction of “any” (≥stage 1), moderate-perisinusoidal (≥stage 1b), moderate-portal/periportal (≥stage 1c), significant (≥stage 2), or advanced (≥stage 3) fibrosis were 0.92/9.28, 0.92/9.33, 0.90/9.54, 0.98/10.18 and 0.99/10.51, respectively.

Conclusions

The ELF test can be used to accurately assess the level of liver fibrosis in pediatric patients with NAFLD. This information is important for identifying patients with progressive fibrosis that require further histopathological analysis or therapeutic follow-up.

Abbreviations used in this paper: ALP, alkaline-phosphate, ALT, alanine aminotransferase, AST, aspartate aminotransferase, AUROC, area under ROC, BMI, body mass index, CI, confidence interval, CLD, chronic liver disease, ELF, enhanced liver fibrosis, HA, hyaluronic acid, HABP, hyaluronic acid binding protein, HOMA, homeostatic model assessment, INR, international normalized ratio, ISI, insulin sensitivity index, IQR, interquartile range, γ-GT, gamma glutamil-transpeptidase, +LR, positive likelihood ratio, −LR, negative likelihood ratio, MAbs, monoclonal antibodies, OC, receiver operating characteristic OGTT, oral glucose tolerance test, NAFLD, nonalcoholic fatty liver disease, NAS, NAFLD Activity Score, NASH, nonalcoholic steatohepatitis, PIIINP, amino-terminal propeptide of type III collagen, PPV, positive predictive value, S, sensitivity, SD, standard deviation, Sp, specificity, NPV, negative predictive value, TIMP-1, tissue inhibitor of metalloproteinase 1