Week 4 Liver Fat Reduction on MRI as an Early Predictor of Treatment Response in Participants with Nonalcoholic Steatohepatitis

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 protondensity 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 MRIbased proton-density fat fraction (PDFF) at week 4 was highly predictive of the treatment response estimated by using the week 12 MRI-based PDFF. (C)RSNA, 2021

Automated summary

Early prediction of treatment response in NASH patients can be achieved by monitoring PDFF changes on MRI, with PDFF changes at week 4 and serum ALP level serving as important predictors for PDFF changes at week 12.