Author information
1Digestive Diseases Unit and CIBERehd, Virgen del Rocío University Hospital, Seville, Spain; Institute of Biomedicine of Seville (HUVR/CSIC/US), University of Seville, Seville, Spain; Department of Diagnostic Radiology, The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital), Zhengzhou, China.
2Digestive Diseases Unit and CIBERehd, Virgen del Rocío University Hospital, Seville, Spain; Institute of Biomedicine of Seville (HUVR/CSIC/US), University of Seville, Seville, Spain.
3Digestive System and Clinical Pharmacology Unit, Virgen de la Victoria University Hospital, Biomedical Research Institute of Malaga and Nanomedicine Platform-IBIMA (Plataforma BIONAND), University of Malaga, Málaga, Spain; Biomedical Research Network Center for Hepatic and Digestive Diseases (CIBERehd), Carlos III Health Institute, Madrid, Spain.
4Department of Gastroenterology, Yokohama City University Graduate School of Medicine; Yokohama, Japan.
5Fatty Liver Program, Division of Digestive and Liver Diseases, Comprehensive Transplant Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
6Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Center for Liver Diseases, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
7Department of Internal Medicine, Gachon University College of Medicine (Gachon University Gil Medical Center), Incheon, South Korea.
8Department of Diagnostic Radiology, Mayo Clinic College of Medicine, Rochester, MN, USA.
9Department of Medical Sciences, Section of Gastroenterology and Hepatology, Uppsala University, Uppsala, Sweden.
10Biostatistics Unit, Department of Preventive Medicine and Public Health, University of Seville, Seville, Spain.
11Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
12Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
13Translational and Clinical Research Institute; Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK; Newcastle NIHR Biomedical Research Centre, Newcastle Upon Tyne Hospitals, NHS Trust, Newcastle Upon Tyne, UK.
14Department of Radiology, Virgen del Rocío University Hospital, Seville, Spain.
15Division of Epidemiology, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA; NAFLD Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
16Digestive Diseases Unit and CIBERehd, Virgen del Rocío University Hospital, Seville, Spain; Institute of Biomedicine of Seville (HUVR/CSIC/US), University of Seville, Seville, Spain. Electronic address: mromerogomez@us.es.
Abstract
Background & aims: We conducted an individual patient data meta-analysis to establish stiffness cut-off values for magnetic resonance elastography (MRE) in staging liver fibrosis and to assess potential confounding factors.
Methods: A systematic review of the literature identified studies reporting MRE data in patients with NAFLD. Data were obtained from the corresponding authors. The pooled diagnostic cut-off value for the various fibrosis stages was determined in a two-stage meta-analysis. Multilevel modelling methods were used to analyse potential confounding factors influencing the diagnostic accuracy of MRE in staging liver fibrosis.
Results: Eight independent cohorts comprising 798 patients were included in the meta-analysis. The area under the receiver operating characteristic curve (AUROC) for MRE in detecting significant fibrosis was 0.92 (sensitivity, 79%; specificity, 89%). For advanced fibrosis, the AUROC was 0.92 (sensitivity, 87%; specificity, 88%). For cirrhosis, the AUROC was 0.94 (sensitivity, 88%, specificity, 89%). Cut-offs were defined to explore concordance between MRE and histopathology: ≥F2, 3.14 kPa (pretest probability, 39.4%); ≥F3, 3.53 kPa (pretest probability, 24.1%); and F4, 4.45 kPa (pretest probability, 8.7%). In generalized linear mixed model analysis, histological steatohepatitis with higher inflammatory activity (odds ratio 2.448, 95% CI 1.180-5.079, p <0.05) and high gamma-glutamyl transferase (GGT) concentration (>120U/L) (odds ratio 3.388, 95% CI 1.577-7.278, p <0.01] were significantly associated with elevated liver stiffness, and thus affecting accuracy in staging early fibrosis (F0-F1). Steatosis, as measured by magnetic resonance imaging proton density fat fraction, and body mass index(BMI) were not confounders.
Conclusions: MRE has excellent diagnostic performance for significant, advanced fibrosis and cirrhosis in patients with NAFLD. Elevated inflammatory activity and GGT level may lead to overestimation of early liver fibrosis, but anthropometric measures such as BMI or the degree of steatosis do not.
Impact and implications: This individual patient data meta-analysis of eight international cohorts, including 798 patients, demonstrated that MRE achieves excellent diagnostic accuracy for significant, advanced fibrosis and cirrhosis in patients with NAFLD. Cut-off values (significant fibrosis, 3.14 kPa; advanced fibrosis, 3.53 kPa; and cirrhosis, 4.45 kPa) were established. Elevated inflammatory activity and gamma-glutamyltransferase level may affect the diagnostic accuracy of MRE, leading to overestimation of liver fibrosis in early stages. We observed no impact of diabetes, obesity, or any other metabolic disorder on the diagnostic accuracy of MRE.