An individual patient data meta-analysis to determine cut-offs for and confounders of NAFLD-fibrosis staging with magnetic resonance elastography
Year: 2023
Type: review
Study designs: Systematic Review, Meta-Analysis
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.
Source: Journal of Hepatology
Institutions: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Biomedicina de Sevilla, Zhengzhou People's Hospital, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Instituto de Salud Carlos III, Instituto de Investigación Biomédica de Málaga, Universidad de Málaga, Yokohama City University, Cedars-Sinai Medical Center, University of Pittsburgh, University of Pittsburgh Medical Center, Gachon University, Gachon University Gil Medical Center, Mayo Clinic, Uppsala University, University of Oxford, NIHR Newcastle Biomedical Research Centre, Newcastle University, University of California San Diego
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,950
Funders: Bristol-Myers Squibb, Pfizer, AstraZeneca, GlaxoSmithKline, Gilead Sciences, Celgene, European Federation of Pharmaceutical Industries and Associations, National Institute for Health and Care Research, Newcastle University, European Commission, Ministry of Health and Welfare, Korea Health Industry Development Institute, Innovative Medicines Initiative, Norgine, National Institutes of Health, Genentech, Allergan, Horizon 2020 Framework Programme, Horizon 2020, NIHR Newcastle Biomedical Research Centre, NIHR Oxford Biomedical Research Centre, National Institute on Alcohol Abuse and Alcoholism, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Biomedical Imaging and Bioengineering, National Center for Advancing Translational Sciences
Awards: G1039249451, G1316440902, G1370780335, G1494183008, G155322889, G1622551803, Liver Investigation: Testing Marker Utility in Steatohepatitis, G2928778974, Novel IL-23 inhibitor for the treatment of alcohol associated liver disease, G434337789, G5278105062, G5680773987, NIHR Senior Investigator Award, G7074422602, G745677937, G7501542120, G8105098291, Alcoholic Hepatitis Clinical and Translational Network Late Phase Clinical Trials and Observational Studies 7/9, G9000110146, San Diego Digestive Diseases Research Center, Clinical Research on Nonalcoholic Fatty Liver Disease, San Diego Cirrhosis Clinical Research Network
OpenAlex ID: W4367301730