title: Clinical Model for NASH and Advanced Fibrosis in Adult Patients With Diabetes and NAFLD: Guidelines for Referral in NAFLD.
abstract: OBJECTIVE
  Approximately 18 million people in the U.S. have coexisting type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). It is not known who among these patients has nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Therefore, we aimed to determine factors that are associated with both NASH and advanced fibrosis in patients with diabetes and NAFLD in order to identify who should be prioritized for referral to a hepatologist for further diagnostic evaluation and treatment.
  
  
  METHODS
  This study was derived from the NASH Clinical Research Network studies and included 1,249 patients with biopsy-proven NAFLD (including a model development cohort of 346 patients and an independent validation cohort of 100 patients with type 2 diabetes as defined by the American Diabetes Association criteria). Outcome measures were presence of NASH or advanced fibrosis (stage 3 or 4) using cross-validated, by jackknife method, multivariable-adjusted area under the receiver operating characteristic curve (AUROC) and 95% CI.
  
  
  RESULTS
  The mean ± SD age and BMI of patients with diabetes and NAFLD was 52.5 ± 10.3 years and 35.8 ± 6.8 kg/m(2), respectively. The prevalence of NASH and advanced fibrosis was 69.2% and 41.0%, respectively. The model for NASH included white race, BMI, waist, alanine aminotransferase (ALT), Aspartate aminotransferase (AST), albumin, HbA1c, HOMA of insulin resistance, and ferritin with an AUROC of 0.80 (95% CI 0.75-0.84, P = 0.007). The specificity, sensitivity, negative predictive values (NPVs), and positive predictive values (PPVs) were 90.0%, 56.8%, 47.7%, and 93.2%, respectively, and the model correctly classified 67% of patients as having NASH. The model for predicting advanced fibrosis included age, Hispanic ethnicity, BMI, waist-to-hip ratio, hypertension, ALT-to-AST ratio, alkaline phosphatase, isolated abnormal alkaline phosphatase, bilirubin (total and direct), globulin, albumin, serum insulin, hematocrit, international normalized ratio, and platelet count with an AUROC of 0.80 (95% CI 0.76-0.85, P < 0.001). The specificity, sensitivity, NPV, and PPV were 90.0%, 57%, 75.1%, and 80.2%, respectively, and the model correctly classified 76.6% of patients as having advanced fibrosis. Results remained consistent for both models in the validation cohort. The proposed model performed better than the NAFLD fibrosis score in detecting advanced fibrosis.
  
  
  CONCLUSIONS
  Routinely available clinical variables can be used to quantify the likelihood of NASH or advanced fibrosis in adult diabetic patients with NAFLD. The clinical models presented can be used to guide clinical decision making about referrals of patients with diabetes and NAFLD to hepatologists.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Bazick
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
authors.forename: Michele
authors.initials: M
authors.lastname: Donithan
authors.affiliation: Division of Gastroenterology and Hepatology, Saint Louis University, St. Louis, MO.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Neuschwander-Tetri
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: David
authors.initials: D
authors.lastname: Kleiner
authors.affiliation: Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Brunt
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
authors.forename: Laura
authors.initials: L
authors.lastname: Wilson
authors.affiliation: Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.
authors.forename: Ed
authors.initials: E
authors.lastname: Doo
authors.affiliation: Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Columbia University, New York, NY.
authors.forename: Joel
authors.initials: J
authors.lastname: Lavine
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
authors.forename: James
authors.initials: J
authors.lastname: Tonascia
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA Divisions of Gastroenterology and Epidemiology, University of California, San Diego, La Jolla, CA roloomba@ucsd.edu.
authors.forename: Rohit
authors.initials: R
authors.lastname: Loomba
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D003661:Decision Support Techniques; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology / Q000628:therapy*; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy*; D017410:Practice Guidelines as Topic; D015995:Prevalence; D012017:Referral and Consultation / Q000592:standards*; D012680:Sensitivity and Specificity; D014481:United States / Q000453:epidemiology