Multicenter Validation of Association Between Decline in MRI‐PDFF and Histologic Response in NASH. Issue 4 (9th October 2020)

• Record Type: Journal Article
• Authors: Loomba, Rohit; Neuschwander‐Tetri, Brent A; Sanyal, Arun; Chalasani, Naga; Diehl, Anna Mae; Terrault, Norah; Kowdley, Kris; Dasarathy, Srinivasan; Kleiner, David; Behling, Cynthia; Lavine, Joel; Van Natta, Mark; Middleton, Michael; Tonascia, James; Sirlin, Claude
• Other Names: Allende Daniela investigator.; Dasarathy Srinivasan investigator.; McCullough Arthur J. investigator.; Penumatsa Revathi investigator.; Dasarathy Jaividhya investigator.; Lavine Joel E. investigator.; Abdelmalek Manal F. investigator.; Bashir Mustafa investigator.; Buie Stephanie investigator.; Diehl Anna Mae investigator.; Guy Cynthia investigator.; Kigongo Christopher investigator.; Kopping Mariko investigator.; Malik David investigator.; Piercy Dawn investigator.; Chalasani Naga investigator.; Cummings Oscar W. investigator.; Gawrieh Samer investigator.; Ragozzino Linda investigator.; Sandrasegaran Kumar investigator.; Vuppalanchi Raj investigator.; Brunt Elizabeth M. investigator.; Cattoor Theresa investigator.; Carpenter Danielle investigator.; Freebersyser Janet investigator.; King Debra investigator.; Lai Jinping investigator.; Neuschwander‐Tetri Brent A. investigator.; Siegner Joan investigator.; Stewart Susan investigator.; Torretta Susan investigator.; Wriston Kristina investigator.; Gonzalez Maria Cardona investigator.; Davila Jodie investigator.; Jhaveri Manan investigator.; Kowdley Kris V. investigator.; Mukhtar Nizar investigator.; Ness Erik investigator.; Poitevin Michelle investigator.; Quist Brook investigator.; Soo Sherilynn investigator.; Ang Brandon investigator.; Behling Cynthia investigator.; Bhatt Archana investigator.; Loomba Rohit investigator.; Middleton Michael S. investigator.; Sirlin Claude investigator.; Akhter Maheen F. investigator.; Bass Nathan M. investigator.; Brandman Danielle investigator.; Gill Ryan investigator.; Hameed Bilal investigator.; Maher Jacqueline investigator.; Terrault Norah investigator.; Ungermann Ashley investigator.; Yeh Matthew investigator.; Boyett Sherry investigator.; Contos Melissa J. investigator.; Kirwin Sherri investigator.; Luketic Velimir A.C. investigator.; Puri Puneet investigator.; Sanyal Arun J. investigator.; Schlosser Jolene investigator.; Siddiqui Mohammad S. investigator.; Yost‐Schomer Leslie investigator.; Brunt Elizabeth M. investigator.; Fowler Kathryn investigator.; Kleiner David E. investigator.; Doo Edward C. investigator.; Hall Sherry investigator.; Hoofnagle Jay H. investigator.; Robuck Patricia R. investigator.; Sherker Averell H. investigator.; Torrance Rebecca investigator.; Belt Patricia investigator.; Clark Jeanne M. investigator.; Dodge John investigator.; Donithan Michele investigator.; Isaacson Milana investigator.; Lazo Mariana investigator.; Meinert Jill investigator.; Miriel Laura investigator.; Sharkey Emily P. investigator.; Smith Jacqueline investigator.; Smith Michael investigator.; Sternberg Alice investigator.; Tonascia James investigator.; Van Natta Mark L. investigator.; Wagoner Annette investigator.; Wilson Laura A. investigator.; Yamada Goro investigator.; Yates Katherine investigator.; Covarrubias Yesenia investigator.; Gamst Anthony investigator.; Hamilton Gavin investigator.; Henderson Walter investigator.; Hooker Jonathan investigator.; Lavine Joel E. investigator.; Loomba Rohit investigator.; Middleton Michael S. investigator.; Schlein Alexandria investigator.; Schwimmer Jeffrey B. investigator.; Shen Wei investigator.; Sirlin Claude investigator.; Wolfson Tanya investigator.;
• Is Part Of: Hepatology. Volume 72:Issue 4(2020)
• Page Start: 1219
• Page End: 1229
• Publication Date: 2020-10-09
• Subjects: Heart -- Diseases -- Nursing -- Periodicals; Lungs -- Diseases -- Nursing -- Periodicals; Intensive care nursing -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1002/hep.31121
• Languages: English
• ISSNs: 0270-9139

Abstract

Abstract : Background and Aims: Emerging data from a single‐center study suggests that a 30% relative reduction in liver fat content as assessed by magnetic resonance imaging–proton density fat fraction (MRI‐PDFF) from baseline may be associated with histologic improvement in nonalcoholic steatohepatitis (NASH). There are limited multicenter data comparing an active drug versus placebo on the association between the quantity of liver fat reduction assessed by MRI‐PDFF and histologic response in NASH. This study aims to examine the association between 30% relative reduction in MRI‐PDFF and histologic response in obeticholic acid (OCA) versus placebo‐treated patients in the FLINT (farnesoid X receptor ligand obeticholic acid in NASH trial). Approach and Results: This is a secondary analysis of the FLINT trial including 78 patients with MRI‐PDFF measured before and after treatment along with paired liver histology assessment. Histologic response was defined as a 2‐point improvement in nonalcoholic fatty liver disease activity score without worsening of fibrosis. OCA (25 mg orally once daily) was better than placebo in improving MRI‐PDFF by an absolute difference of −3.4% (95% confidence interval [CI], −6.5 to −0.2%, P value = 0.04) and relative difference of −17% (95% CI, −34 to 0%, P value = 0.05). The optimal cutoff point for relative decline in MRI‐PDFF for histologic response was 30% (using Youden's index). The rate of histologic response in those who achieved less than 30% decline in MRI‐PDFF versus those who achieved a 30% or greater decline in MRI‐PDFF ( MRI‐PDFF responders ) relative to baseline was 19% versus 50%, respectively. Compared with MRI‐PDFF nonresponders, MRI‐PDFF responders demonstrated both a statistically and clinically significant higher odds 4.86 (95% CI, 1.4‐12.8, P value < 0.009) of histologic response, including significant improvements in both steatosis and ballooning. Conclusion: OCA was better than placebo in reducing liver fat. This multicenter trial provides data regarding the association between 30% decline in MRI‐PDFF relative to baseline and histologic response in NASH.