Agreement Between Magnetic Resonance Imaging Proton Density Fat Fraction Measurements and Pathologist-Assigned Steatosis Grades of Liver Biopsies From Adults With Nonalcoholic Steatohepatitis

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Abstract

Background & Aims We assessed the diagnostic performance of magnetic resonance imaging (MRI) proton density fat fraction (PDFF) in grading hepatic steatosis and change in hepatic steatosis in adults with nonalcoholic steatohepatitis (NASH) in a multi-center study, using central histology as reference. Methods We collected data from 113 adults with NASH participating in a multi-center, randomized, double-masked, placebo-controlled, phase 2b trial to compare the efficacy cross-sectionally and longitudinally of obeticholic acid vs placebo. Hepatic steatosis was assessed at baseline and after 72 weeks of obeticholic acid or placebo by liver biopsy and MRI (scanners from different manufacturers, at 1.5T or 3T). We compared steatosis estimates by PDFF vs histology. Histologic steatosis grade was scored in consensus by a pathology committee. Cross-validated receiver operating characteristic (ROC) analyses were performed. Results At baseline, 34% of subjects had steatosis grade 0 or 1, 39% had steatosis grade 2, and 27% had steatosis grade 3; corresponding mean PDFF values were 9.8%±3.7%, 18.1%±4.3%, and 30.1%±8.1%. PDFF classified steatosis grade 0–1 vs 2–3 with an area under the ROC curve (AUROC) of 0.95 (95% CI, 0.91–0.98), and grade 0–2 vs grade 3 steatosis with an AUROC of 0.96 (95% CI, 0.93–0.99). PDFF cut-off values at 90% specificity were 16.3% for grades 2–3 and 21.7% for grade 3, with corresponding sensitivities of 83% and 84%. After 72 weeks' of obeticholic vs placebo, 42% of subjects had a reduced steatosis grade (mean reduction in PDFF from baseline of 7.4%±8.7%), 49% had no change in steatosis grade (mean increase in PDFF from baseline of 0.3%±6.3%), and 9% had an increased steatosis grade (mean increase in PDFF from baseline of 7.7%±6.0%). PDFF change identified subjects with reduced steatosis grade with an AUROC of 0.81 (95% CI, 0.71–0.91) and increased steatosis grade with an AUROC of 0.81 (95% CI, 0.63–0.99). A PDFF reduction of 5.15% identified subjects with reduced steatosis grade with 90% specificity and 58% sensitivity, whereas a PDFF increase of 5.6% identified those with increased steatosis grade with 90% specificity and 57% sensitivity. Conclusions Based on data from a phase 2 randomized controlled trial of adults with NASH, PDFF estimated by MRI scanners of different field strength and at different sites, accurately classifies grades and changes in hepatic steatosis when histologic analysis of biopsies is used as a reference.

Original languageEnglish (US)
Pages (from-to)753-761
Number of pages9
JournalGastroenterology
Volume153
Issue number3
DOIs
StatePublished - Sep 1 2017

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Fatty Liver
Protons
Fats
Magnetic Resonance Imaging
Biopsy
ROC Curve
Placebos
Liver
Area Under Curve
Pathologists
Non-alcoholic Fatty Liver Disease
Histology
Sensitivity and Specificity
Randomized Controlled Trials
Pathology

Keywords

  • Direct Comparison
  • FLINT
  • NAFLD
  • Non-Invasive

ASJC Scopus subject areas

  • Gastroenterology

Cite this

@article{0b006919ecdb41938969090638aa6fca,
title = "Agreement Between Magnetic Resonance Imaging Proton Density Fat Fraction Measurements and Pathologist-Assigned Steatosis Grades of Liver Biopsies From Adults With Nonalcoholic Steatohepatitis",
abstract = "Background & Aims We assessed the diagnostic performance of magnetic resonance imaging (MRI) proton density fat fraction (PDFF) in grading hepatic steatosis and change in hepatic steatosis in adults with nonalcoholic steatohepatitis (NASH) in a multi-center study, using central histology as reference. Methods We collected data from 113 adults with NASH participating in a multi-center, randomized, double-masked, placebo-controlled, phase 2b trial to compare the efficacy cross-sectionally and longitudinally of obeticholic acid vs placebo. Hepatic steatosis was assessed at baseline and after 72 weeks of obeticholic acid or placebo by liver biopsy and MRI (scanners from different manufacturers, at 1.5T or 3T). We compared steatosis estimates by PDFF vs histology. Histologic steatosis grade was scored in consensus by a pathology committee. Cross-validated receiver operating characteristic (ROC) analyses were performed. Results At baseline, 34{\%} of subjects had steatosis grade 0 or 1, 39{\%} had steatosis grade 2, and 27{\%} had steatosis grade 3; corresponding mean PDFF values were 9.8{\%}±3.7{\%}, 18.1{\%}±4.3{\%}, and 30.1{\%}±8.1{\%}. PDFF classified steatosis grade 0–1 vs 2–3 with an area under the ROC curve (AUROC) of 0.95 (95{\%} CI, 0.91–0.98), and grade 0–2 vs grade 3 steatosis with an AUROC of 0.96 (95{\%} CI, 0.93–0.99). PDFF cut-off values at 90{\%} specificity were 16.3{\%} for grades 2–3 and 21.7{\%} for grade 3, with corresponding sensitivities of 83{\%} and 84{\%}. After 72 weeks' of obeticholic vs placebo, 42{\%} of subjects had a reduced steatosis grade (mean reduction in PDFF from baseline of 7.4{\%}±8.7{\%}), 49{\%} had no change in steatosis grade (mean increase in PDFF from baseline of 0.3{\%}±6.3{\%}), and 9{\%} had an increased steatosis grade (mean increase in PDFF from baseline of 7.7{\%}±6.0{\%}). PDFF change identified subjects with reduced steatosis grade with an AUROC of 0.81 (95{\%} CI, 0.71–0.91) and increased steatosis grade with an AUROC of 0.81 (95{\%} CI, 0.63–0.99). A PDFF reduction of 5.15{\%} identified subjects with reduced steatosis grade with 90{\%} specificity and 58{\%} sensitivity, whereas a PDFF increase of 5.6{\%} identified those with increased steatosis grade with 90{\%} specificity and 57{\%} sensitivity. Conclusions Based on data from a phase 2 randomized controlled trial of adults with NASH, PDFF estimated by MRI scanners of different field strength and at different sites, accurately classifies grades and changes in hepatic steatosis when histologic analysis of biopsies is used as a reference.",
keywords = "Direct Comparison, FLINT, NAFLD, Non-Invasive",
author = "{for the} and Middleton, {Michael S.} and Heba, {Elhamy R.} and Hooker, {Catherine A.} and Bashir, {Mustafa R.} and Fowler, {Kathryn J.} and Kumar Sandrasegaran and Brunt, {Elizabeth M.} and Kleiner, {David E.} and Edward Doo and {Van Natta}, {Mark L.} and Lavine, {Joel E.} and Neuschwander-Tetri, {Brent A.} and Arun Sanyal and Rohit Loomba and Sirlin, {Claude B.}",
year = "2017",
month = "9",
day = "1",
doi = "10.1053/j.gastro.2017.06.005",
language = "English (US)",
volume = "153",
pages = "753--761",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "3",

}

TY - JOUR

T1 - Agreement Between Magnetic Resonance Imaging Proton Density Fat Fraction Measurements and Pathologist-Assigned Steatosis Grades of Liver Biopsies From Adults With Nonalcoholic Steatohepatitis

AU - for the

AU - Middleton, Michael S.

AU - Heba, Elhamy R.

AU - Hooker, Catherine A.

AU - Bashir, Mustafa R.

AU - Fowler, Kathryn J.

AU - Sandrasegaran, Kumar

AU - Brunt, Elizabeth M.

AU - Kleiner, David E.

AU - Doo, Edward

AU - Van Natta, Mark L.

AU - Lavine, Joel E.

AU - Neuschwander-Tetri, Brent A.

AU - Sanyal, Arun

AU - Loomba, Rohit

AU - Sirlin, Claude B.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Background & Aims We assessed the diagnostic performance of magnetic resonance imaging (MRI) proton density fat fraction (PDFF) in grading hepatic steatosis and change in hepatic steatosis in adults with nonalcoholic steatohepatitis (NASH) in a multi-center study, using central histology as reference. Methods We collected data from 113 adults with NASH participating in a multi-center, randomized, double-masked, placebo-controlled, phase 2b trial to compare the efficacy cross-sectionally and longitudinally of obeticholic acid vs placebo. Hepatic steatosis was assessed at baseline and after 72 weeks of obeticholic acid or placebo by liver biopsy and MRI (scanners from different manufacturers, at 1.5T or 3T). We compared steatosis estimates by PDFF vs histology. Histologic steatosis grade was scored in consensus by a pathology committee. Cross-validated receiver operating characteristic (ROC) analyses were performed. Results At baseline, 34% of subjects had steatosis grade 0 or 1, 39% had steatosis grade 2, and 27% had steatosis grade 3; corresponding mean PDFF values were 9.8%±3.7%, 18.1%±4.3%, and 30.1%±8.1%. PDFF classified steatosis grade 0–1 vs 2–3 with an area under the ROC curve (AUROC) of 0.95 (95% CI, 0.91–0.98), and grade 0–2 vs grade 3 steatosis with an AUROC of 0.96 (95% CI, 0.93–0.99). PDFF cut-off values at 90% specificity were 16.3% for grades 2–3 and 21.7% for grade 3, with corresponding sensitivities of 83% and 84%. After 72 weeks' of obeticholic vs placebo, 42% of subjects had a reduced steatosis grade (mean reduction in PDFF from baseline of 7.4%±8.7%), 49% had no change in steatosis grade (mean increase in PDFF from baseline of 0.3%±6.3%), and 9% had an increased steatosis grade (mean increase in PDFF from baseline of 7.7%±6.0%). PDFF change identified subjects with reduced steatosis grade with an AUROC of 0.81 (95% CI, 0.71–0.91) and increased steatosis grade with an AUROC of 0.81 (95% CI, 0.63–0.99). A PDFF reduction of 5.15% identified subjects with reduced steatosis grade with 90% specificity and 58% sensitivity, whereas a PDFF increase of 5.6% identified those with increased steatosis grade with 90% specificity and 57% sensitivity. Conclusions Based on data from a phase 2 randomized controlled trial of adults with NASH, PDFF estimated by MRI scanners of different field strength and at different sites, accurately classifies grades and changes in hepatic steatosis when histologic analysis of biopsies is used as a reference.

AB - Background & Aims We assessed the diagnostic performance of magnetic resonance imaging (MRI) proton density fat fraction (PDFF) in grading hepatic steatosis and change in hepatic steatosis in adults with nonalcoholic steatohepatitis (NASH) in a multi-center study, using central histology as reference. Methods We collected data from 113 adults with NASH participating in a multi-center, randomized, double-masked, placebo-controlled, phase 2b trial to compare the efficacy cross-sectionally and longitudinally of obeticholic acid vs placebo. Hepatic steatosis was assessed at baseline and after 72 weeks of obeticholic acid or placebo by liver biopsy and MRI (scanners from different manufacturers, at 1.5T or 3T). We compared steatosis estimates by PDFF vs histology. Histologic steatosis grade was scored in consensus by a pathology committee. Cross-validated receiver operating characteristic (ROC) analyses were performed. Results At baseline, 34% of subjects had steatosis grade 0 or 1, 39% had steatosis grade 2, and 27% had steatosis grade 3; corresponding mean PDFF values were 9.8%±3.7%, 18.1%±4.3%, and 30.1%±8.1%. PDFF classified steatosis grade 0–1 vs 2–3 with an area under the ROC curve (AUROC) of 0.95 (95% CI, 0.91–0.98), and grade 0–2 vs grade 3 steatosis with an AUROC of 0.96 (95% CI, 0.93–0.99). PDFF cut-off values at 90% specificity were 16.3% for grades 2–3 and 21.7% for grade 3, with corresponding sensitivities of 83% and 84%. After 72 weeks' of obeticholic vs placebo, 42% of subjects had a reduced steatosis grade (mean reduction in PDFF from baseline of 7.4%±8.7%), 49% had no change in steatosis grade (mean increase in PDFF from baseline of 0.3%±6.3%), and 9% had an increased steatosis grade (mean increase in PDFF from baseline of 7.7%±6.0%). PDFF change identified subjects with reduced steatosis grade with an AUROC of 0.81 (95% CI, 0.71–0.91) and increased steatosis grade with an AUROC of 0.81 (95% CI, 0.63–0.99). A PDFF reduction of 5.15% identified subjects with reduced steatosis grade with 90% specificity and 58% sensitivity, whereas a PDFF increase of 5.6% identified those with increased steatosis grade with 90% specificity and 57% sensitivity. Conclusions Based on data from a phase 2 randomized controlled trial of adults with NASH, PDFF estimated by MRI scanners of different field strength and at different sites, accurately classifies grades and changes in hepatic steatosis when histologic analysis of biopsies is used as a reference.

KW - Direct Comparison

KW - FLINT

KW - NAFLD

KW - Non-Invasive

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U2 - 10.1053/j.gastro.2017.06.005

DO - 10.1053/j.gastro.2017.06.005

M3 - Article

VL - 153

SP - 753

EP - 761

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 3

ER -