title: Association of noninvasive quantitative decline in liver fat content on MRI with histologic response in nonalcoholic steatohepatitis.
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.
authors: Department of Internal Medicine, University of California at San Diego, La Jolla, CA, USA.
authors: Janki
authors: J
authors: Patel
authors: 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.
authors: Ricki
authors: R
authors: Bettencourt
authors: NAFLD Translational Research Unit, Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
authors: Jeffrey
authors: J
authors: Cui
authors: 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.
authors: Joanie
authors: J
authors: Salotti
authors: Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, USA.
authors: Jonathan
authors: J
authors: Hooker
authors: NAFLD Translational Research Unit, Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
authors: Archana
authors: A
authors: Bhatt
authors: NAFLD Translational Research Unit, Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
authors: Carolyn
authors: C
authors: Hernandez
authors: 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.
authors: Phirum
authors: P
authors: Nguyen
authors: Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, USA.
authors: Hamed
authors: H
authors: Aryafar
authors: Department of Pathology, University of California at San Diego, La Jolla, CA, USA.
authors: Mark
authors: M
authors: Valasek
authors: Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, USA.
authors: William
authors: W
authors: Haufe
authors: Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, USA.
authors: Catherine
authors: C
authors: Hooker
authors: 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.
authors: Lisa
authors: L
authors: Richards
authors: Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, USA.
authors: Claude B
authors: CB
authors: Sirlin
authors: 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.
authors: Rohit
authors: R
authors: Loomba
keywords: MRI-proton-density-fat-fraction (PDFF); advanced fibrosis; biomarker; fat mapping; magnetic resonance imaging (MRI); nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; noninvasive assessment