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.
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.
Authors: Xi-Xi Wu; Kenneth I Zheng; Jérôme Boursier; Wah-Kheong Chan; Yusuf Yilmaz; Manuel Romero-Gómez; Mohamed El Kassas; Giovanni Targher; Christopher D Byrne; Zhi-Ming Huang; Ming-Hua Zheng Journal: EClinicalMedicine Date: 2021-10-01
Authors: Ferenc Emil Mózes; Jenny A Lee; Emmanuel Anandraj Selvaraj; Arjun Narayan Ajmer Jayaswal; Michael Trauner; Jerome Boursier; Céline Fournier; Katharina Staufer; Rudolf E Stauber; Elisabetta Bugianesi; Ramy Younes; Silvia Gaia; Monica Lupșor-Platon; Salvatore Petta; Toshihide Shima; Takeshi Okanoue; Sanjiv Mahadeva; Wah-Kheong Chan; Peter J Eddowes; Gideon M Hirschfield; Philip Noel Newsome; Vincent Wai-Sun Wong; Victor de Ledinghen; Jiangao Fan; Feng Shen; Jeremy F Cobbold; Yoshio Sumida; Akira Okajima; Jörn M Schattenberg; Christian Labenz; Won Kim; Myoung Seok Lee; Johannes Wiegand; Thomas Karlas; Yusuf Yılmaz; Guruprasad Padur Aithal; Naaventhan Palaniyappan; Christophe Cassinotto; Sandeep Aggarwal; Harshit Garg; Geraldine J Ooi; Atsushi Nakajima; Masato Yoneda; Marianne Ziol; Nathalie Barget; Andreas Geier; Theresa Tuthill; M Julia Brosnan; Quentin Mark Anstee; Stefan Neubauer; Stephen A Harrison; Patrick M Bossuyt; Michael Pavlides Journal: Gut Date: 2021-05-17 Impact factor: 23.059