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

Leung, Daniel H., Khan, Mahjabeen, Minard, Charles G., Guffey, Danielle, Ramm, Louise E., Clouston, Andrew D., Miller, Gregory, Lewindon, Peter J., Shepherd, Ross W. and Ramm, Grant A. (2015) Aspartate aminotransferase to platelet ratio and fibrosis-4 as biomarkers in biopsy-validated pediatric cystic fibrosis liver disease. Hepatology, 62 5: 1576-1583. doi:10.1002/hep.28016


Author Leung, Daniel H.
Khan, Mahjabeen
Minard, Charles G.
Guffey, Danielle
Ramm, Louise E.
Clouston, Andrew D.
Miller, Gregory
Lewindon, Peter J.
Shepherd, Ross W.
Ramm, Grant A.
Title Aspartate aminotransferase to platelet ratio and fibrosis-4 as biomarkers in biopsy-validated pediatric cystic fibrosis liver disease
Journal name Hepatology   Check publisher's open access policy
ISSN 1527-3350
0270-9139
Publication date 2015-11-01
Year available 2015
Sub-type Article (original research)
DOI 10.1002/hep.28016
Open Access Status Not Open Access
Volume 62
Issue 5
Start page 1576
End page 1583
Total pages 8
Place of publication Hoboken, NJ, United States
Publisher John Wiley and Sons
Language eng
Abstract 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 (>1.5x 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. (Hepatology 2015;62:1576-1583)
Formatted abstract
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. (Hepatology 2015;62:1576–1583)
Keyword Gastroenterology & Hepatology
Gastroenterology & Hepatology
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID APP1048740
APP1061332
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Faculty of Medicine
Official 2016 Collection
School of Medicine Publications
 
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