An individual patient data meta-analysis to determine cut-offs for and confounders of NAFLD-fibrosis staging with magnetic resonance elastography

•Magnetic resonance elastography demonstrated excellent diagnostic accuracy for staging liver fibrosis in patients with NAFLD.•Assessment of fibrosis was not confounded by steatosis or high body mass index.•Cut-offs for significant fibrosis, advanced fibrosis, and cirrhosis were found to be 3.14, 3.53, and 4.45 kPa, respectively.•Raised GGT levels and increased lobular inflammatory activity may result in overestimation of early-stage fibrosis (F0–F1). Background & AimsWe 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.MethodsA 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.ResultsEight 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.ConclusionsMRE 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 implicationsThis 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. 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. 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. 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. 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.