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Aliment Pharmacol Ther. 2017 Mar;45(6):844-854. doi: 10.1111/apt.13951. Epub 2017 Jan 24.

Assessment of treatment response in non-alcoholic steatohepatitis using advanced magnetic resonance imaging.

Author information

1
Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
2
NAFLD Research Center, University of California at San Diego, La Jolla, CA, USA.
3
Liver Imaging Group, Department of Radiology, University of California at San Diego, La Jolla, CA, USA.
4
Division of Epidemiology, Department of Family Medicine and Public Health, University of California at San Diego, La Jolla, CA, USA.
5
Department of Pathology, University of California at San Diego, La Jolla, CA, USA.
6
Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
7
Division of Gastroenterology, University of California at San Diego, La Jolla, CA, USA.

Abstract

BACKGROUND:

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.

AIM:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
28116801
PMCID:
PMC5346270
DOI:
10.1111/apt.13951
[Indexed for MEDLINE]
Free PMC Article

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