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  • Title: Aspartate aminotransferase to platelet ratio and fibrosis-4 as biomarkers in biopsy-validated pediatric cystic fibrosis liver disease.
    Author: Leung DH, Khan M, Minard CG, Guffey D, Ramm LE, Clouston AD, Miller G, Lewindon PJ, Shepherd RW, Ramm GA.
    Journal: Hepatology; 2015 Nov; 62(5):1576-83. PubMed ID: 26223427.
    Abstract:
    UNLABELLED: Up to 10% of cystic fibrosis (CF) children develop cirrhosis by the first decade. We evaluated the utility of two simple biomarkers, aspartate aminotransferase to platelet ratio index (APRI) and FIB-4, in predicting degree of fibrosis in pediatric CF 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 sex-matched CF children without liver disease (CFnoLD) had serum to calculate APRI and FIB-4 collected at enrollment. CFLD was defined as having two of the following: (1) hepatomegaly±splenomegaly; (2)>6 months elevation of ALT (>1.5× upper limit of normal ULN); or (3) abnormal liver ultrasound findings. Biopsies were staged according to Metavir classification by two blinded pathologists. Receiver operating characteristic (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 cut-off 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-F4) (0.81). An APRI score>0.264 demonstrated a sensitivity (95% confidence interval [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 one stage 73% of the time. Only FIB-4 predicted portal hypertension at diagnosis (area under the receiver operator characteristic curve [AUC 0.91; P<0.001). CONCLUSION: 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 versus CFnoLD. APRI also exhibited a high AUC in predicting severe liver fibrosis with specific cutoffs for lower stages.
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