Aspartate aminotransferase to platelet ratio and fibrosis‐4 as biomarkers in biopsy‐validated pediatric cystic fibrosis liver disease

Daniel H Leung, Mahjabeen Khan, Charles G Minard, Danielle Guffey, Louise E Ramm, Andrew D Clouston, Gregory Miller, Peter J Lewindon, Ross W Shepherd, Grant A Ramm

Up to 10% of CF children develop cirrhosis by the first decade. We evaluated the utility of 2 simple biomarkers, APRi and FIB-4 in predicting the degree of fibrosis in pediatric cystic fibrosis liver disease (CFLD) validated by liver biopsy. In this retrospective cross-sectional study, 67 children with CFLD had dual pass liver biopsies and 104 age and gender matched CF children without liver disease (CFnoLD) had serum to calculate APRi and FIB-4 collected at enrollment. CFLD was defined as having 2 of the following: 1) hepatomegaly ± splenomegaly, 2) >6 months elevation of ALT (>1.5x ULN), or 3) abnormal liver ultrasound findings. Biopsies were staged according to Metavir classification by two blinded pathologists. ROC analysis and continuation ratio logistic regression were performed to assess the predictability of these biomarkers to distinguish CFLD from CFnoLD and determine fibrosis stage specific cutoff values. The AUC for APRi was better than FIB-4 (0.75 vs 0.60, p=0.005) for predicting CFLD and severe CFLD (F3-4) (0.81). An APRi score > 0.264 demonstrated a sensitivity (95% CI) of 73.1% (60.9,83.2) and specificity of 70.2% (60.4, 78.8) in predicting CFLD. A 50% increase in APRi was associated with a 2.4 fold (95% CI: 1.7,3.3) increased odds of having CFLD. APRi demonstrated full agreement with histology staging 37% of the time, but was within 1 stage 73% of the time. Only FIB-4 predicted portal hypertension at diagnosis (AUC=0.91, p<0.001). This is the first liver biopsy validated study of APRi and FIB-4 in pediatric CFLD. APRi appears superior to FIB-4 in differentiating CFLD vs CFnoLD. APRi also exhibited a high AUC in predicting severe liver fibrosis with specific cut-offs for lower stages. This article is protected by copyright. All rights reserved.