Longitudinal correlations between MRE, MRI-PDFF, and liver histology in patients with non-alcoholic steatohepatitis: Analysis of data from a phase II trial of selonsertib

Background & Aims: Non-invasive tools for monitoring treatment response and disease progression in non-alcoholic steatohepatitis (NASH) are needed. Our objective was to evaluate the utility of magnetic resonance (MR)-based hepatic imaging measures for the assessment of liver histology in patients with NASH. Methods: We analyzed data from patients with NASH and stage 2 or 3 fibrosis enrolled in a phase II study of selonsertib. Pre-and post-treatment assessments included centrally read MR elastography (MRE)-estimated liver stiffness, MR imaging-estimated proton density fat fraction (MRI-PDFF), and liver biopsies evaluated according to the NASH Clinical Research Network classification and the non-alcoholic fatty liver disease activity score (NAS). Results: Among 54 patients with MRE and biopsies at baseline and week 24, 18 (33%) had fibrosis improvement (>= 1-stage reduction) after undergoing 24 weeks of treatment with the study drug. The area under the receiver operating characteristic curve (AUROC) of MRE-stiffness to predict fibrosis improvement was 0.62 (95% CI 0.46-0.78) and the optimal threshold was a >= 0% relative reduction. At this threshold, MRE had 67% sensitivity, 64% specificity, 48% positive predictive value, 79% negative predictive value. Among 65 patients with MRI-PDFF and biopsies at baseline and week 24, a >= 1-grade reduction in steatosis was observed in 18 (28%). The AUROC of MRI-PDFF to predict steatosis response was 0.70 (95% CI 0.57-0.83) and the optimal threshold was a >= 0% relative reduction. At this threshold, MRI-PDFF had 89% sensitivity and 47% specificity, 39% positive predictive value, and 92% negative predictive value. Conclusions: These preliminary data support the further evaluation of MRE-stiffness and MRI-PDFF for the longitudinal assessment of histologic response in patients with NASH. Lay summary: Liver biopsy is a potentially painful and risky method to assess damage to the liver due to non-alcoholic steatohepatitis (NASH). We analyzed data from a clinical trial to determine if 2 methods of magnetic resonance imaging - 1 to measure liver fat and 1 to measure liver fibrosis (scarring) - could potentially replace liver biopsy in evaluating NASH-related liver injury. Both imaging methods were correlated with biopsy in showing the effects of NASH on the liver. (C) 2018 European Association for the Study of the Liver. Published by Elsevier B.V.