Multicenter Validation of Association Between Decline in MRI‐PDFF and Histologic Response in NASH
Year: 2020
Type: article
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.
Source: Hepatology
DOI: 10.1002/hep.31121
Institutions: University of California San Diego, Saint Louis University, Virginia Commonwealth University, Virginia Commonwealth University Medical Center, Indiana University Hospital, Indiana University Indianapolis, Duke University, University of California, San Francisco, Swedish Medical Center, Cleveland Clinic, National Institutes of Health, National Cancer Institute, Columbia University Irving Medical Center, Columbia University, Johns Hopkins University
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network, San Diego Clinical and Translational Research Institute, Institute of Translational Health Sciences, Duke CTSA, Center for Clinical and Translational Research, Center for Clinical and Translational Research, Multidisciplinary Clinical and Translational Science (MCTS) Program (UL1), Clinical and Translational Science Institute, Atlanta Clinical and Translational Science Institute (ACTSI) Renewal, QUS Technology for Diagnosis and Grading of Hepatic Steatosis in NAFLD, Washington University Institute of Clinical and Translational Sciences, Institute for Clinical and Translational Research, Johns Hopkins Institute for Clinical and Translational Research, Indiana Clinical and Translational Science Institute (UL1), Clinical and Translational Science Award, Clinical and Translational Science Collaborative of Cleveland, Cincinnati Center for Clinical and Translational Sciences and Training, Clinical and Translational Science Collaborative of Cleveland, UC San Diego Clinical and Translational Research Institute, Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN), Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN), Data Coordinating Center for the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Continuation, San Diego Digestive Diseases Research Center, Clinical Research Network in Nonalcoholic Steatohepatitis, Collaborative Clinical Research in Nonalcoholic Steatohepatitis, Washington University Institute of Clinical and Translational Sciences, Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Clinical Center-Cleveland site, Clinical Research on Nonalcoholic Fatty Liver Disease, The Saint Louis University Component of the NASH Clinical Research Network, Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)
OpenAlex ID: W3001786135