Multicenter Validation of Association Between Decline in MRI-PDFF and Histologic Response in NASH
Rohit Loomba, Brent A Neuschwander-Tetri, Arun Sanyal, Naga Chalasani, Anna Mae Diehl, Norah Terrault, Kris Kowdley, Srinivasan Dasarathy, David Kleiner, Cynthia Behling, Joel Lavine, Mark Van Natta, Michael Middleton, James Tonascia, Claude Sirlin, NASH Clinical Research Network, Daniela Allende, Srinivasan Dasarathy, Arthur J McCullough, Revathi Penumatsa, Jaividhya Dasarathy, Joel E Lavine, Manal F Abdelmalek, Mustafa Bashir, Stephanie Buie, Anna Mae Diehl, Cynthia Guy, Christopher Kigongo, Mariko Kopping, David Malik, Dawn Piercy, Naga Chalasani, Oscar W Cummings, Samer Gawrieh, Linda Ragozzino, Kumar Sandrasegaran, Raj Vuppalanchi, Elizabeth M Brunt, Theresa Cattoor, Danielle Carpenter, Janet Freebersyser, Debra King, Jinping Lai, Brent A Neuschwander-Tetri, Joan Siegner, Susan Stewart, Susan Torretta, Kristina Wriston, Maria Cardona Gonzalez, Jodie Davila, Manan Jhaveri, Kris V Kowdley, Nizar Mukhtar, Erik Ness, Michelle Poitevin, Brook Quist, Sherilynn Soo, Brandon Ang, Cynthia Behling, Archana Bhatt, Rohit Loomba, Michael S Middleton, Claude Sirlin, Maheen F Akhter, Nathan M Bass, Danielle Brandman, Ryan Gill, Bilal Hameed, Jacqueline Maher, Norah Terrault, Ashley Ungermann, Matthew Yeh, Sherry Boyett, Melissa J Contos, Sherri Kirwin, Velimir A C Luketic, Puneet Puri, Arun J Sanyal, Jolene Schlosser, Mohammad S Siddiqui, Leslie Yost-Schomer, Elizabeth M Brunt, Kathryn Fowler, David E Kleiner, Edward C Doo, Sherry Hall, Jay H Hoofnagle, Patricia R Robuck, Averell H Sherker, Rebecca Torrance, Patricia Belt, Jeanne M Clark, John Dodge, Michele Donithan, Milana Isaacson, Mariana Lazo, Jill Meinert, Laura Miriel, Emily P Sharkey, Jacqueline Smith, Michael Smith, Alice Sternberg, James Tonascia, Mark L Van Natta, Annette Wagoner, Laura A Wilson, Goro Yamada, Katherine Yates, Yesenia Covarrubias, Anthony Gamst, Gavin Hamilton, Walter Henderson, Jonathan Hooker, Joel E Lavine, Rohit Loomba, Michael S Middleton, Alexandria Schlein, Jeffrey B Schwimmer, Wei Shen, Claude Sirlin, Tanya Wolfson, Rohit Loomba, Brent A Neuschwander-Tetri, Arun Sanyal, Naga Chalasani, Anna Mae Diehl, Norah Terrault, Kris Kowdley, Srinivasan Dasarathy, David Kleiner, Cynthia Behling, Joel Lavine, Mark Van Natta, Michael Middleton, James Tonascia, Claude Sirlin, NASH Clinical Research Network, Daniela Allende, Srinivasan Dasarathy, Arthur J McCullough, Revathi Penumatsa, Jaividhya Dasarathy, Joel E Lavine, Manal F Abdelmalek, Mustafa Bashir, Stephanie Buie, Anna Mae Diehl, Cynthia Guy, Christopher Kigongo, Mariko Kopping, David Malik, Dawn Piercy, Naga Chalasani, Oscar W Cummings, Samer Gawrieh, Linda Ragozzino, Kumar Sandrasegaran, Raj Vuppalanchi, Elizabeth M Brunt, Theresa Cattoor, Danielle Carpenter, Janet Freebersyser, Debra King, Jinping Lai, Brent A Neuschwander-Tetri, Joan Siegner, Susan Stewart, Susan Torretta, Kristina Wriston, Maria Cardona Gonzalez, Jodie Davila, Manan Jhaveri, Kris V Kowdley, Nizar Mukhtar, Erik Ness, Michelle Poitevin, Brook Quist, Sherilynn Soo, Brandon Ang, Cynthia Behling, Archana Bhatt, Rohit Loomba, Michael S Middleton, Claude Sirlin, Maheen F Akhter, Nathan M Bass, Danielle Brandman, Ryan Gill, Bilal Hameed, Jacqueline Maher, Norah Terrault, Ashley Ungermann, Matthew Yeh, Sherry Boyett, Melissa J Contos, Sherri Kirwin, Velimir A C Luketic, Puneet Puri, Arun J Sanyal, Jolene Schlosser, Mohammad S Siddiqui, Leslie Yost-Schomer, Elizabeth M Brunt, Kathryn Fowler, David E Kleiner, Edward C Doo, Sherry Hall, Jay H Hoofnagle, Patricia R Robuck, Averell H Sherker, Rebecca Torrance, Patricia Belt, Jeanne M Clark, John Dodge, Michele Donithan, Milana Isaacson, Mariana Lazo, Jill Meinert, Laura Miriel, Emily P Sharkey, Jacqueline Smith, Michael Smith, Alice Sternberg, James Tonascia, Mark L Van Natta, Annette Wagoner, Laura A Wilson, Goro Yamada, Katherine Yates, Yesenia Covarrubias, Anthony Gamst, Gavin Hamilton, Walter Henderson, Jonathan Hooker, Joel E Lavine, Rohit Loomba, Michael S Middleton, Alexandria Schlein, Jeffrey B Schwimmer, Wei Shen, Claude Sirlin, Tanya Wolfson
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.
Trial registration: ClinicalTrials.gov NCT01265498.
© 2020 by the American Association for the Study of Liver Diseases.
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Source: PubMed