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Abstract Details
Week 4 Liver Fat Reduction on MRI as an Early Predictor of Treatment Response in Participants with Nonalcoholic Steatohepatitis
Radiology. 2021 Jun 1;204325. doi: 10.1148/radiol.2021204325. Online ahead of print.
Hanyu Jiang1, Hubert C Chen1, Kyle J Lafata1, Mustafa R Bashir1
Author information
1From the Department of Radiology (H.J., K.J.L., M.R.B.), Center for Advanced MR Development (M.R.B.), Division of Gastroenterology, Department of Medicine (M.R.B.), and Department of Radiation Oncology (K.J.L.), Duke University Medical Center, School of Medicine, and Department of Electrical and Computer Engineering, Pratt School of Engineering (K.J.L.), Duke University, Box 3808, Durham, NC 27710; Department of Radiology, West China Hospital, Sichuan University, Chengdu, China (H.J.); and Metacrine, San Diego, Calif (H.C.C.).
Abstract
Background Pharmacologic treatment of nonalcoholic steatohepatitis (NASH) is long term in nature; thus, early noninvasive treatment response assessment is important for therapeutic decision making. Purpose To investigate potential early predictors of the 12-week treatment response estimated by using the MRI-based proton-density fat fraction (PDFF). Materials and Methods In this secondary analysis of a prospective phase Ib clinical trial evaluating a candidate treatment (MET409, a farnesoid X receptor agonist) for NASH, participants were analyzed at baseline and at 4 and 12 weeks after either active treatment with MET409 or placebo treatment between June 2019 and January 2020. Correlation and multiple linear regression analyses were used to identify clinical, laboratory, and imaging predictors of the relative PDFF change at week 12 (W12). Multivariate logistic regression analysis was used to develop predictive models for an at least 30% relative PDFF reduction at W12, a well-validated indicator of histologic improvement. Model performance was characterized by using area under the receiver operating characteristic curve (AUC) analysis, sensitivity, and specificity. Results A total of 48 participants were analyzed (median age, 57 years; age range, 40-62 years; 32 women), among whom 30 received MET409 and 18 received a placebo. The week 4 (W4) relative changes in PDFF (regression coefficient = 1.24, P < .001) and the serum alkaline phosphatase (ALP) level (regression coefficient = -0.29, P = .03) were predictors of the W12 relative PDFF change. An at least 19.3% relative PDFF reduction at W4 yielded an AUC of 0.98 (sensitivity, 89%; specificity, 95%) for predicting an at least 30% relative PDFF reduction at W12. The addition of ALP to the predictive model did not improve model performance. Conclusion In participants with nonalcoholic steatohepatitis enrolled in a phase Ib treatment trial, the relative change in the MRI-based proton-density fat fraction (PDFF) at week 4 was highly predictive of the treatment response estimated by using the week 12 MRI-based PDFF.