The development of the Pediatric NAFLD Fibrosis Score (PNFS) to predict the presence of advanced fibrosis in children with nonalcoholic fatty liver disease

Naim Alkhouri, Sana Mansoor, Paola Giammaria, Daniela Liccardo, Rocio Lopez, Valerio Nobili

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: 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. Methods: Consecutive 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. Results: Our 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 = 1006exp(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. Conclusion: Noninvasive 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.

Original languageEnglish
Article numbere104558
JournalPLoS One
Volume9
Issue number8
DOIs
Publication statusPublished - Aug 14 2014

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Pediatrics
fatty liver
Platelets
fibrosis
Liver
Fibrosis
Alkaline Phosphatase
Logistics
Biopsy
Regression analysis
Probability distributions
Blood Platelets
Non-alcoholic Fatty Liver Disease
liver cirrhosis
Logistic Models
alkaline phosphatase
blood platelet count

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

The development of the Pediatric NAFLD Fibrosis Score (PNFS) to predict the presence of advanced fibrosis in children with nonalcoholic fatty liver disease. / Alkhouri, Naim; Mansoor, Sana; Giammaria, Paola; Liccardo, Daniela; Lopez, Rocio; Nobili, Valerio.

In: PLoS One, Vol. 9, No. 8, e104558, 14.08.2014.

Research output: Contribution to journalArticle

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abstract = "Background: 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. Methods: Consecutive 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. Results: Our 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 = 1006exp(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. Conclusion: Noninvasive 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.",
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