title: Utility of magnetic resonance imaging versus histology for quantifying changes in liver fat in nonalcoholic fatty liver disease trials.
abstract: The magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) is a novel imaging-based biomarker that allows fat mapping of the entire liver, whereas the magnetic resonance spectroscopy-measured proton density fat fraction (MRS-PDFF) provides a biochemical measure of liver fat in small regions of interest. Cross-sectional studies have shown that MRI-PDFF correlates with MRS-PDFF. The aim of this study was to show the utility of MRI-PDFF in assessing quantitative changes in liver fat through a three-way comparison of MRI-PDFF and MRS-PDFF with the liver histology-determined steatosis grade at two time points in patients with nonalcoholic fatty liver disease (NAFLD). Fifty patients with biopsy-proven NAFLD who participated in a randomized trial underwent a paired evaluation with liver biopsy, MRI-PDFF, and MRS-PDFF at the baseline and 24 weeks. The mean age and body mass index were 47.8 ± 11.7 years and 30.7 ± 6.5 kg/m(2), respectively. MRI-PDFF showed a robust correlation with MRS-PDFF both at week 0 and at week 24 (r = 0.98, P < 0.0001 for both). Cross-sectionally, MRI-PDFF and MRS-PDFF increased with increases in the histology-determined steatosis grade both at week 0 and at week 24 (P < 0.05 for all). Longitudinally, patients who had a decrease (≥ 1%) or increase (≥ 1%) in MRI-PDFF (confirmed by MRS-PDFF) showed a parallel decrease or increase in their body weight and serum alanine aminotransferase and aspartate aminotransferase levels at week 24 (P < 0.05). This small increase or decrease in liver fat could not be quantified with histology.
  
  
  CONCLUSIONS
  In this longitudinal study, MRI-PDFF correlated well with MRS-PDFF and was more sensitive than the histology-determined steatosis grade in quantifying increases or decreases in the liver fat content. Therefore, it could be used to quantify changes in liver fat in future clinical trials.
authors.affiliation: Departments of Medicine (Division of Gastroenterology), University of California San Diego, San Diego, CA.
authors.forename: Mazen
authors.initials: M
authors.lastname: Noureddin
authors.forename: Jessica
authors.initials: J
authors.lastname: Lam
authors.forename: Michael R
authors.initials: MR
authors.lastname: Peterson
authors.forename: Michael
authors.initials: M
authors.lastname: Middleton
authors.forename: Gavin
authors.initials: G
authors.lastname: Hamilton
authors.forename: Thuy-Anh
authors.initials: TA
authors.lastname: Le
authors.forename: Ricki
authors.initials: R
authors.lastname: Bettencourt
authors.forename: Chris
authors.initials: C
authors.lastname: Changchien
authors.forename: David A
authors.initials: DA
authors.lastname: Brenner
authors.forename: Claude
authors.initials: C
authors.lastname: Sirlin
authors.forename: Rohit
authors.initials: R
authors.lastname: Loomba
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D001706:Biopsy; D001835:Body Weight; D005234:Fatty Liver / Q000473:pathology*; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease
chemical_list: D015415:Biomarkers