Clinical utility of 30% relative decline in MRI-PDFF in predicting fibrosis regression in non-alcoholic fatty liver disease.

OBJECTIVE: Emerging data suggest that a 30% relative decline in liver fat, as assessed by MRI-proton density fat fraction (MRI-PDFF), may be associated with Non-Alcoholic Fatty Liver Disease Activity Score improvement, but the association between decline in MRI-PDFF and fibrosis regression is not known. Therefore, we aimed to examine the association between ≥30% relative decline in MRI-PDFF and fibrosis regression in non-alcoholic fatty liver disease (NAFLD). DESIGN: This prospective study included 100 well-characterised patients with biopsy-proven NAFLD with paired contemporaneous MRI-PDFF assessment at two time points. MRI-PDFF response was defined as ≥30% relative decline in MRI-PDFF. The primary outcome was ≥1 stage histological fibrosis regression. RESULTS: The median (IQR) age was 54 (43-62) years and body mass index was 31.9 (29-36) kg/m2. In multivariable-adjusted logistic regression analysis (adjusted for age, gender, diabetes status, race/ethnicity, interval between biopsies, gamma-glutamyl transferase, liver stiffness by magnetic resonance elastography and change in platelet counts), MRI-PDFF response was an independent predictor of fibrosis regression with an adjusted OR of 6.46 (95% CI 1.1 to 37.0, p=0.04). The proportion of patients with MRI-PDFF response with fibrosis regression, no change in fibrosis and fibrosis progression was 40.0%, 24.6% and 13.0%, respectively, and the proportion of patients with MRI-PDFF response increased with fibrosis regression (p=0.03). CONCLUSION: ≥30% reduction in MRI-PDFF in early phase trials can provide a useful estimate of odds of ≥1 stage improvement in fibrosis. These data may be helpful in sample size estimation in non-alcoholic steatohepatitis trials.

Clinical Utility of Change in Nonalcoholic Fatty Liver Disease Activity Score and Change in Fibrosis in NAFLD.

The Nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) has been applied as a method for evaluating treatment response, and a ≥2-point improvement in NAS has been commonly used as an accepted end point in phase 2b clinical trials in nonalcoholic steatohepatitis.1,2 Although liver fibrosis is the strongest histologic predictor of liver-related outcome and all-cause mortality in NAFLD,3,4 the association between change in NAS and change in fibrosis stage has not been fully verified. Therefore, we aimed to examine the association between change in NAS and change in fibrosis stage in well-characterized patients with NAFLD who had a paired liver biopsy assessment.