title: Assessment of treatment response in non-alcoholic steatohepatitis using advanced magnetic resonance imaging.
abstract: Magnetic resonance imaging-derived measures of liver fat and volume are emerging as accurate, non-invasive imaging biomarkers in non-alcoholic steatohepatitis (NASH). Little is known about these measures in relation to histology longitudinally.
  
  
  
  To examine any relationship between MRI-derived proton-density fat-fraction (PDFF), total liver volume (TLV), total liver fat index (TLFI), vs. histology in a NASH trial.
  
  
  
  This is a secondary analysis of a 24-week randomised, double-blind, placebo-controlled trial of 50 patients with biopsy-proven NASH randomised to oral ezetimibe 10 mg daily (n = 25) vs. placebo (n = 25). Baseline and post-treatment anthropometrics, biochemical profiling, MRI and biopsies were obtained.
  
  
  
  Baseline mean PDFF correlated strongly with TLFI (Spearman's ρ = 0.94, n = 45, P < 0.0001) and had good correlation with TLV (ρ = 0.57, n = 45, P < 0.0001). Mean TLV correlated strongly with TLFI (ρ = 0.78, n = 45, P < 0.0001). After 24 weeks, PDFF remained strongly correlated with TLFI (ρ = 0.94, n = 45, P < 0.0001), maintaining good correlation with TLV (ρ = 0.51, n = 45, P = 0.0004). TLV remained strongly correlated with TLFI (ρ = 0.74, n = 45, P < 0.0001). Patients with Grade 1 vs. 3 steatosis had lower PDFF, TLV, and TLFI (P < 0.0001, P = 0.0003, P < 0.0001 respectively). Regression analysis of changes in MRI-PDFF vs. TLV indicates that 10% reduction in MRI-PDFF predicts 257 mL reduction in TLV.
  
  
  
  The MRI-PDFF and TLV strongly correlated with TLFI. Decreases in steatosis were associated with an improvement in hepatomegaly. Lower values of these measures reflect lower histologic steatosis grades. MRI-derived measures of liver fat and volume may be used as dynamic and more responsive imaging biomarkers in a NASH trial, than histology.
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|NAFLD Research Center, University of California at San Diego, La Jolla, CA, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Lin
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Heba
authors.affiliation: NAFLD Research Center, University of California at San Diego, La Jolla, CA, USA.|Division of Epidemiology, Department of Family Medicine and Public Health, University of California at San Diego, La Jolla, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Bettencourt
authors.affiliation: Department of Pathology, University of California at San Diego, La Jolla, CA, USA.
authors.forename: G Y
authors.initials: GY
authors.lastname: Lin
authors.affiliation: Department of Pathology, University of California at San Diego, La Jolla, CA, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Valasek
authors.affiliation: Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
authors.forename: O
authors.initials: O
authors.lastname: Lunde
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Hamilton
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, USA.
authors.forename: C B
authors.initials: CB
authors.lastname: Sirlin
authors.affiliation: NAFLD Research Center, University of California at San Diego, La Jolla, CA, USA.|Division of Epidemiology, Department of Family Medicine and Public Health, University of California at San Diego, La Jolla, CA, USA.|Division of Gastroenterology, University of California at San Diego, La Jolla, CA, USA.
authors.forename: R
authors.identifier: 0000-0002-4845-9991
authors.initials: R
authors.lastname: Loomba
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D003430:Cross-Sectional Studies; D018752:Diet, Fat-Restricted / Q000379:methods; D004311:Double-Blind Method; D000069438:Ezetimibe / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D015415:Biomarkers; D000069438:Ezetimibe