Association of noninvasive quantitative decline in liver fat content on MRI with histologic response in nonalcoholic steatohepatitis

Janki Patel; Ricki Bettencourt; Jeffrey Cui; Joanie Salotti; Jonathan Hooker; Archana Bhatt; Carolyn Hernandez; Phirum Nguyen; Hamed Aryafar; Mark Valasek; William Haufe; Catherine Hooker; Lisa Richards; Claude B Sirlin; Rohit Loomba

doi:10.1177/1756283X16656735

Association of noninvasive quantitative decline in liver fat content on MRI with histologic response in nonalcoholic steatohepatitis

Therap Adv Gastroenterol. 2016 Sep;9(5):692-701. doi: 10.1177/1756283X16656735. Epub 2016 Jul 5.

Authors

Affiliations

¹ Department of Internal Medicine, University of California at San Diego, La Jolla, CA, USA.
² NAFLD Translational Research Unit, Department of Medicine, University of California at San Diego, La Jolla, CA, USA Division of Epidemiology, Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, CA, USA.
³ NAFLD Translational Research Unit, Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
⁴ NAFLD Translational Research Unit, Department of Medicine, University of California at San Diego, La Jolla, CA, USA Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
⁵ Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, USA.
⁶ Department of Pathology, University of California at San Diego, La Jolla, CA, USA.
⁷ NAFLD Translational Research Unit, Division of Gastroenterology and Epidemiology, University of California at San Diego, 9500 Gilman Drive, MC 0063, La Jolla, CA 92093, USA.

Abstract

Background: Magnetic resonance imaging-estimated proton-density-fat-fraction (MRI-PDFF) has been shown to be a noninvasive, accurate and reproducible imaging-based biomarker for assessing steatosis and treatment response in nonalcoholic steatohepatitis (NASH) clinical trials. However, there are no data on the magnitude of MRI-PDFF reduction corresponding to histologic response in the setting of a NASH clinical trial. The aim of this study was to quantitatively compare the magnitude of MRI-PDFF reduction between histologic responders versus histologic nonresponders in NASH patients.

Methods: This study is a secondary analysis of the MOZART trial, which included 50 patients with biopsy-proven NASH randomized to ezetimibe 10 mg/day orally or placebo for 24 weeks. The primary aim was to perform a head-to-head comparative analysis of histologic responders [defined as a ⩾2-point reduction in the nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) without worsening fibrosis] versus nonresponders, and the corresponding quantitative change in liver fat content measured via MRI-PDFF.

Results: Of the 35 patients who underwent paired liver biopsy and MRI-PDFF assessment at the beginning and end of treatment, 10 demonstrated a histologic response. Compared with histologic nonresponders, histologic responders had a statistically significant reduction in MRI-PDFF of -4.1% ± 4.9 versus -0.6 ± 4.1 (p < 0.04) with a mean relative percent change of -29.3% ± 33.0 versus +2.0% ± 24.0 (p < 0.004), respectively.

Conclusions: Utilizing paired MRI-PDFF and liver histology data, we demonstrate that a relative reduction of 29% in liver fat on MRI-PDFF is associated with a histologic response in NASH. After external validation by independent research groups, these results can be incorporated into designing future NASH clinical trials, especially those utilizing change in hepatic fat quantified by MRI-PDFF, as a treatment endpoint.

Keywords: MRI-proton-density-fat-fraction (PDFF); advanced fibrosis; biomarker; fat mapping; magnetic resonance imaging (MRI); nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; noninvasive assessment.

Grants and funding

K23 DK090303/DK/NIDDK NIH HHS/United States