Development and Validation of a Score for Fibrotic Non-Alcoholic Steatohepatitis

Background and aims: Non-invasive assessment of histological features of non-alcoholic fatty liver disease (NAFLD) has been an intensive research area over the last decade. Herein, we aimed to develop a simple non-invasive score using routine laboratory tests to identify, among individuals at high risk for NAFLD, those with fibrotic non-alcoholic steatohepatitis (NASH) defined as NASH, NAFLD activity score (NAS) ≥4, and fibrosis stage ≥2. Methods: The derivation cohort included 264 morbidly obese individuals undergoing intraoperative liver biopsy in Rome, Italy. The best predictive model was developed and internally validated using a bootstrapping stepwise logistic regression analysis (2000 bootstrap samples). Performance was estimated by the area under the receiver operating characteristic curve (AUROC). External validation was assessed in three independent European cohorts (Finland, n=370; Italy n=947; England n=5,368) of individuals at high risk for NAFLD. Results: The final predictive model, designated as Fibrotic NASH Index (FNI), combined aspartate aminotransferase (AST), high-density lipoprotein (HDL) cholesterol, and hemoglobin A1c (HbA1c). The performance of FNI for fibrotic NASH was satisfactory in both derivation and external validation cohorts (AUROCs 0.78 and 0.80-0.95, respectively). In the derivation cohort, rule-out and rule-in cut-offs were 0.10 for sensitivity ≥0.89 (negative predictive value [NPV] 0.93) and 0.33 for specificity ≥0.90 (positive predictive value [PPV] 0.57), respectively. In the external validation cohorts, sensitivity ranged from 0.87 to 1 (NPV 0.99-1) and specificity from 0.73 to 0.94 (PPV 0.12-0.49) for rule-out and rule-in cut-off, respectively. Conclusion: FNI is an accurate, simple, and affordable non-invasive score which can be used in primary healthcare to screen for fibrotic NASH individuals with dysmetabolism.