Usefulness of the index of NASH – ION for the diagnosis of steatohepatitis in patients with non‐alcoholic fatty liver: An external validation study

Background & Aims The non‐invasive identification of steatohepatitis (NASH) in patients with Non‐Alcoholic Fatty Liver Disease is an unmet need in clinical practice. Index of NASH (ION) is a new tool for the prediction of NASH. We aimed to externally validate ION and to compare it with CK‐18. Since necroinflammation precedes fibrosis, we also tested ION in combination with non‐invasive tools for fibrosis. Methods We analysed data from 292 Italian patients (169 Southern cohort, and 123 Northern cohort) with an histological diagnosis of NAFLD. The ION, FIB‐4 and NFS scores were calculated according to published algorithms. Serum cytokeratin18‐Aspartate396 levels and liver stiffness (LS) by Fibroscan were assessed within three months from liver biopsy. Results The diagnostic accuracy of ION for the identification of NASH was not as satisfactory as reported (area under the ROC curve, AUROC = 0.687 [95% CI = 0.62‐0.75]). The proposed cut‐off value ≥50 showed a poor sensitivity (Se) (28%) and a good specificity (Sp) (92%), with a positive predictive value (PPV) of 91% and a negative predictive value (NPV) of 30%. A new cut‐off value >26 improved Se (73%) but decreased Sp (60%) (PPV of 84% and a NPV of 43%). ION performed slightly better in obese NAFLD (AUROC = 0.700). The combination of ION and markers of fibrosis did not improve the identification of advanced liver disease. Conclusions ION is not feasible for the non‐invasive diagnosis of NASH across different populations of NAFLD patients, mainly because its limited reproducibility in non‐obese subjects.