Abstract
BackgroundNoninvasive hepatic fibrosis scores that predict the presence of advanced fibrosis have been developed and validated in adult patients with NAFLD. The aims of our study were to assess the utility of commonly used adult fibrosis scores in pediatric NAFLD and to develop a pediatric specific fibrosis score that can predict advanced fibrosis.MethodsConsecutive children with biopsy-proven NAFLD were included. Fibrosis was determined by an experienced pathologist (F0–4). Advanced fibrosis was defined as fibrosis stage ≥3. The following adult fibrosis scores were calculated for each child: AST/ALT ratio, AST/platelet ratio index (APRI), NAFLD fibrosis score (NFS), and FIB-4 Index. Multivariable logistic regression analysis was performed to build a new pediatric model for predicting advanced fibrosis.ResultsOur cohort consisted of 242 children with a mean age of 12.4±3.1 years and 63% were female. 36 (15%) subjects had advanced fibrosis. APRI and FIB-4 were higher in patients with advanced fibrosis compared to those with fibrosis stage 0–2; however, AST/ALT ratio and NFS were not different between the two groups. We used our data to develop a new model to predict advanced fibrosis which included: ALT, alkaline phosphatase, platelet counts and GGT. The multivariable logistic regression model (z) was defined as follows: z = 1.1+(0.34*sqrt(ALT))+(0.002*alkaline phosphatase) – (1.1*log(platelets) – (0.02*GGT). This value was then converted into a probability distribution (p) with a value between 0 to 100 by the following formula: p = 100×exp(z)/[1+exp(z)]. The AUCROC for this model was 0.74 (95% CI: 0.66, 0.82). This was found to be significantly better than APRI, NAFLD Fibrosis Score and FIB-4 Index.ConclusionNoninvasive hepatic fibrosis scores developed in adults had poor performance in diagnosing advanced fibrosis in children with NAFLD. We developed a new pediatric NAFLD fibrosis score with improved performance characteristics.
Highlights
Due to the epidemic of childhood obesity, nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children [1,2]
Several noninvasive fibrosis scoring systems comprised of routinely measured clinical and laboratory variables have been developed in adult patients with NAFLD to identify those with advanced fibrosis including the AST/ALT ratio, NAFLD fibrosis score (NFS), the AST/platelet ratio index (APR), and the FIB4-score [5]
The main findings of this large study in children with biopsy-proven NAFLD are that: (1) simple noninvasive scores that have been validated to predict advanced fibrosis in adult patients with NAFLD are not accurate in children, (2) the newly developed Pediatric NAFLD Fibrosis Score (PNFS) is more accurate than AST/platelet ratio index (APRI), FIB-4 index or NFS for predicting the presence of advanced fibrosis in children with fatty liver disease and may become a useful tool to determine patients that need more intensive evaluation and management
Summary
Due to the epidemic of childhood obesity, nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children [1,2]. Pediatric NAFLD is relatively benign but some children can develop major hepatic complications including cirrhosis and the need for liver transplantation [3]. The presence of advanced fibrosis, which includes bridging fibrosis and cirrhosis, may be the most important factor in determining the prognosis of NAFLD and its risk of progression to end-stage liver disease. Children with bridging fibrosis are very likely to progress to developing cirrhosis in the absence of effective treatment for NAFLD which requires close monitoring for signs of portal hypertension and hepatic decompensation. There is an urgent need to develop simple noninvasive tests to identify children with advanced fibrosis. Noninvasive hepatic fibrosis scores that predict the presence of advanced fibrosis have been developed and validated in adult patients with NAFLD. The aims of our study were to assess the utility of commonly used adult fibrosis scores in pediatric NAFLD and to develop a pediatric specific fibrosis score that can predict advanced fibrosis
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