TY - JOUR
T1 - Multicenter Validation of Association Between Decline in MRI-PDFF and Histologic Response in NASH
AU - the NASH Clinical Research Network
AU - Loomba, Rohit
AU - Neuschwander-Tetri, Brent A.
AU - Sanyal, Arun J.
AU - Chalasani, Naga
AU - Diehl, Anna Mae
AU - Terrault, Norah
AU - Kowdley, Kris V.
AU - Dasarathy, Srinivasan
AU - Kleiner, David E.
AU - Behling, Cynthia
AU - Lavine, Joel E.
AU - Van Natta, Mark L.
AU - Middleton, Michael S.
AU - Tonascia, James
AU - Sirlin, Claude
AU - Allende, Daniela
AU - McCullough, Arthur J.
AU - Penumatsa, Revathi
AU - Dasarathy, Jaividhya
AU - Abdelmalek, Manal F.
AU - Bashir, Mustafa
AU - Buie, Stephanie
AU - Guy, Cynthia
AU - Kigongo, Christopher
AU - Kopping, Mariko
AU - Malik, David
AU - Piercy, Dawn
AU - Cummings, Oscar W.
AU - Gawrieh, Samer
AU - Ragozzino, Linda
AU - Sandrasegaran, Kumar
AU - Vuppalanchi, Raj
AU - Brunt, Elizabeth M.
AU - Cattoor, Theresa
AU - Carpenter, Danielle
AU - Freebersyser, Janet
AU - King, Debra
AU - Lai, Jinping
AU - Siegner, Joan
AU - Stewart, Susan
AU - Torretta, Susan
AU - Wriston, Kristina
AU - Gonzalez, Maria Cardona
AU - Davila, Jodie
AU - Jhaveri, Manan
AU - Mukhtar, Nizar
AU - Ness, Erik
AU - Poitevin, Michelle
AU - Quist, Brook
AU - Soo, Sherilynn
N1 - Funding Information:
Support: The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, and U01DK061713). Additional support was received from the National Center for Advancing Translational Sciences (UL1TR000439, UL1TR000077, UL1TR000436, UL1TR000150, UL1TR000424, UL1TR000006, UL1TR000448, UL1TR000040, UL1TR000100, UL1TR000004, UL1TR000423, UL1TR000058, and UL1TR000454). This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. The FLINT trial was conducted by the NASH CRN and supported in part by a Collaborative Research and Development Agreement between NIDDK and Intercept Pharmaceuticals (FLINT: NCT01265498).
Funding Information:
This is a secondary analysis of the FLINT trial: a multicenter, randomized, double‐masked, placebo‐controlled, phase 2b clinical trial in which patients without cirrhosis with biopsy‐proven NASH were randomized to either OCA (25 mg orally daily) or placebo for 72 weeks. The FLINT trial included 283 patients who were recruited at eight sites of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN), a consortium funded by the National Institute of Diabetes and Digestive and Kidney Diseases. All participants provided written informed consent, and the studies were approved by the institutional review boards of the participating centers.
Publisher Copyright:
© 2020 by the American Association for the Study of Liver Diseases.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85088419374&partnerID=8YFLogxK
U2 - 10.1002/hep.31121
DO - 10.1002/hep.31121
M3 - Article
C2 - 31965579
AN - SCOPUS:85088419374
VL - 72
SP - 1219
EP - 1229
JO - Hepatology
JF - Hepatology
SN - 0270-9139
IS - 4
ER -