title: The development of the pediatric NAFLD fibrosis score (PNFS) to predict the presence of advanced fibrosis in children with nonalcoholic fatty liver disease.
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 = 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatric Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, United States of America; Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Naim
authors.initials: N
authors.lastname: Alkhouri
authors.affiliation: Department of Pediatric Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Sana
authors.initials: S
authors.lastname: Mansoor
authors.affiliation: The Liver Unit, Bambino Gesu Children's Hospital, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Giammaria
authors.affiliation: The Liver Unit, Bambino Gesu Children's Hospital, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Liccardo
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Rocio
authors.initials: R
authors.lastname: Lopez
authors.affiliation: The Liver Unit, Bambino Gesu Children's Hospital, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Nobili
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D001219:Aspartate Aminotransferases; D001706:Biopsy; D001792:Blood Platelets / Q000378:metabolism; D002648:Child; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D016015:Logistic Models; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism / Q000473:pathology*; D010976:Platelet Count / Q000379:methods; D012720:Severity of Illness Index
chemical_list: D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase