title: The development of a non-invasive model to predict the presence of non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease.
abstract: BACKGROUND
  Non-alcoholic steatohepatitis (NASH) is an advanced and aggressive form of non-alcoholic fatty liver disease (NAFLD), which remains difficult to diagnose without a liver biopsy. Hyperferritinemia has increasingly been associated with the presence of NASH. Hence, we sought to explore the relationship between ferritin and NASH and to develop a composite model based on ferritin to predict the presence of NASH.
  
  
  METHODS
  A total of 405 patients with biopsy-proven NAFLD were enrolled in the study. Comparison was explored to assess differences between patients with and without NASH, upon which a scoring model was established using variables found to be independent predictors of NASH.
  
  
  RESULTS
  Among all patients with NAFLD, 291 (72%) had biopsy-proven NASH, and 114 (28%) had non-NASH. Mean age was 48 ± 12 years, and 56% were female. Ferritin was significantly higher in NASH compared with non-NASH patients (184 vs 126, respectively; P < 0.001) but lacked diagnostic accuracy for predicting NASH alone (area under the curve [AUC 0.62]). The addition of other significant variables such as aspartate aminotransferase, body mass index, platelet count, diabetes, and hypertension to ferritin improved the prediction of NASH with an AUC 0.81 (95% confidence interval: 0.76-0.86). Internal validation of the model using imputed data sets demonstrated that AUC did not change materially.
  
  
  CONCLUSIONS
  While higher ferritin was significantly associated with NASH, ferritin alone lacked diagnostic accuracy to predict NASH. However, incorporating several easily obtainable variables with ferritin allowed the construction of a novel scoring system that can be easily applied in the clinical setting to guide management of NAFLD.
authors.affiliation: Department of Gastroenterology, Metrohealth Medical Center, Cleveland, Ohio, USA.
authors.forename: George Bb
authors.initials: GB
authors.lastname: Goh
authors.affiliation: Department of Gastroenterology, Metrohealth Medical Center, Cleveland, Ohio, USA.|Department of Gastroenterology, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Danny
authors.initials: D
authors.lastname: Issa
authors.affiliation: Quantitative Health Services, Metrohealth Medical Center, Cleveland, Ohio, USA.
authors.forename: Rocio
authors.initials: R
authors.lastname: Lopez
authors.affiliation: Department of Gastroenterology, Metrohealth Medical Center, Cleveland, Ohio, USA.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Dasarathy
authors.affiliation: Departments of Family Practice, Cleveland Clinic at the Cleveland Clinic Lerner College of Medicine at Case Western University, Richmond, Virginia, USA.
authors.forename: Jaividhya
authors.initials: J
authors.lastname: Dasarathy
authors.affiliation: Department of Gastroenterology, Metrohealth Medical Center, Cleveland, Ohio, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Sargent
authors.affiliation: Gastroenterology, Cleveland Clinic at the Cleveland Clinic Lerner College of Medicine at Case Western University, Cleveland, Ohio, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Hawkins
authors.affiliation: Pathology, Metrohealth Medical Center, Richmond, Virginia, USA.
authors.forename: Rish K
authors.initials: RK
authors.lastname: Pai
authors.affiliation: Pathology, Metrohealth Medical Center, Richmond, Virginia, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Yerian
authors.affiliation: Pathology, Metrohealth Medical Center, Cleveland Clinic at the Cleveland Clinic Lerner College of Medicine at Case Western University, Cleveland, Ohio, USA.
authors.forename: Amer
authors.initials: A
authors.lastname: Khiyami
authors.affiliation: Department of Gastroenterology, Metrohealth Medical Center, Cleveland, Ohio, USA.
authors.forename: Mangesh R
authors.initials: MR
authors.lastname: Pagadala
authors.affiliation: Department of Gastroenterology, Metrohealth Medical Center, Cleveland, Ohio, USA.
authors.forename: Achuthan
authors.initials: A
authors.lastname: Sourianarayanane
authors.affiliation: Department of Gastroenterology, Metrohealth Medical Center, Cleveland, Ohio, USA.|Pediatric Gastroenterology, Cleveland Clinic at the Cleveland Clinic Lerner College of Medicine at Case Western University, Richmond, Virginia, USA.
authors.forename: Naim
authors.initials: N
authors.lastname: Alkhouri
authors.affiliation: Department of Gastroenterology, Metrohealth Medical Center, Cleveland, Ohio, USA.
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: McCullough
mesh_terms: D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D003430:Cross-Sectional Studies; D003661:Decision Support Techniques; D018450:Disease Progression; D005260:Female; D005293:Ferritins / Q000097:blood*; D006304:Health Status; D006305:Health Status Indicators; D006801:Humans; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000175:diagnosis*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D005293:Ferritins
keywords: NAFLD; NASH < hepatology; clinical < hepatology; pathogenesis < hepatology