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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.

  • Author(s): Jayakumar, Saumya
  • Middleton, Michael S
  • Lawitz, Eric J
  • Mantry, Parvez S
  • Caldwell, Stephen H
  • Arnold, Hays
  • Mae Diehl, Anna
  • Ghalib, Reem
  • Elkhashab, Magdy
  • Abdelmalek, Manal F
  • Kowdley, Kris V
  • Stephen Djedjos, C
  • Xu, Ren
  • Han, Ling
  • Mani Subramanian, G
  • Myers, Robert P
  • Goodman, Zachary D
  • Afdhal, Nezam H
  • Charlton, Michael R
  • Sirlin, Claude B
  • Loomba, Rohit
  • et al.
Abstract

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.

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