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

Abstract

ObjectiveEmerging 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).DesignThis 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.ResultsThe 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.

Non-invasive tests of non-alcoholic fatty liver disease

“…Several studies have shown a correlation between a reduction in MRI-PDFF (usually taken as a ≥30% relative reduction) and a 2-point improvement in the NAFLD activity score, resolution of NASH, and fibrosis improvement. [ 35 , 36 ] This test has been used as an end point to examine efficacy of various drugs to assess treatment response in several early phase trials in NASH. However, the MRI-PDFF response is probably drug-specific, and some studies have failed to demonstrate an association with histologic response.…”

“…MRI-PDFF response is a potential surrogate for histologic improvement. Several studies have shown a correlation between a reduction in MRI-PDFF (usually taken as a ≥30% relative reduction) and a 2-point improvement in the NAFLD activity score, resolution of NASH, and fibrosis improvement [35,36] . This test has been used as an end point to examine efficacy of various drugs to assess treatment response in several early phase trials in NASH.…”

Longitudinal association of magnetic resonance elastography‐associated liver stiffness with complications and mortality

“…Furthermore, magnetic resonance imaging (MRI)-based assessment of liver features including proton density fat fraction (PDFF) is better than histological evaluation in assessing quantitative changes in liver features. [39][40][41]…”

Letter: association of laboratory indexes and magnetic resonance elastography‐associated liver stiffness with complications and mortality—authors' reply

“…Emerging data suggest that magnetic resonance imaging-proton density fat fraction (MRI-PDFF) is better than histology to assess clinical changes. 3,4 Change in MRI-PDFF is associated with change in fibrosis 5 and, furthermore, changes in MRE are associated with changes in fibrosis. 6 As a prognostic factor, MRE may be better than liver biopsy, because MRE can evaluate fibrosis status from minimal fibrosis through to decompensation.…”