1Sezione di Gastroenterologia, PROMISE, University of Palermo, Italy.
2Department of Economics and Statistics, University of Palermo, Palermo, Italy.
3NIHR Nottingham Biomedical Research Centre (BRC), Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.
4Nottingham Digestive Diseases Centre, Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK.
5Department of Gastroenterology, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey.
6Hepato-Gastroenterology Department, Angers University Hospital, Angers, France.
7HIFIH Laboratory, UPRES EA3859, Angers University, Angers, France.
8Department of Diagnostic and Interventional Radiology, Saint-Eloi Hospital, University Hospital of Montpellier, Montpellier, France.
9Hepatology Unit, University Hospital Bordeaux and INSERM U-1053, Bordeaux University, Pessac, France.
10Department of Medicine, Faculty of Medicine, University of Malaya, Malaysia.
11Department of Oncology, Gastroenterology, Hepatology, Pulmonology and Infectious Diseases, University Hospital Leipzig, Leipzig, Germany.
12Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong.
13Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
14Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
15Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea.
16Department of Medical Imaging, Iuliu Hatieganu, University of Medicine and Pharmacy, Regional Institute of Gastroenterology and Hepatology "Prof. Dr. Octavian Fodor", Cluj-Napoca, Romania.
17Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
18Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
19Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria.
20Division of Transplantation, Department of General Surgery, Medical University of Vienna, Austria.
21Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Austria.
22Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan.
23Division of Gastroenterology and Hepatology, Department of Medical Sciences, University of Turin, Italy.
24Department of Hepatology, MAFLD Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
25Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China.
26Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK.
27Newcastle NIHR Biomedical Research Center, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, Tyne and Wear, UK.
28Radcliffe Department of Medical Sciences, Cardiovascular Medicine, University of Oxford, Oxford, UK.
Background and aims: We evaluated the diagnostic accuracy of simple, noninvasive tests (NITs) in NAFLD patients with type 2 diabetes (T2D).
Methods and results: This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score (NFS), aspartate aminotransferase-to-platelet ratio index, liver stiffness measurement (LSM) by vibration-controlled transient elastography, and AGILE 3+. The target conditions were advanced fibrosis, NASH, and fibrotic NASH(NASH plus F2-F4 fibrosis). The diagnostic performance of noninvasive tests. individually or in sequential combination, was assessed by area under the receiver operating characteristic curve and by decision curve analysis. Comparison with 2278 NAFLD patients without T2D was also made. In NAFLD with T2D LSM and AGILE 3+ outperformed, both NFS and FIB-4 for advanced fibrosis (area under the receiver operating characteristic curve:LSM 0.82, AGILE 3+ 0.82, NFS 0.72, FIB-4 0.75, aspartate aminotransferase-to-platelet ratio index 0.68; p < 0.001 of LSM-based versus simple serum tests), with an uncertainty area of 12%-20%. The combination of serum-based with LSM-based tests for advanced fibrosis led to a reduction of 40%-60% in necessary LSM tests. Decision curve analysis showed that all scores had a modest net benefit for ruling out advanced fibrosis at the risk threshold of 5%-10% of missing advanced fibrosis. LSM and AGILE 3+ outperformed both NFS and FIB-4 for fibrotic NASH (area under the receiver operating characteristic curve:LSM 0.79, AGILE 3+ 0.77, NFS 0.71, FIB-4 0.71; p < 0.001 of LSM-based versus simple serum tests). All noninvasive scores were suboptimal for diagnosing NASH.
Conclusions: LSM and AGILE 3+ individually or in low availability settings in sequential combination after FIB-4 or NFS have a similar good diagnostic accuracy for advanced fibrosis and an acceptable diagnostic accuracy for fibrotic NASH in NAFLD patients with T2D.