Utility of magnetic resonance imaging versus histology for quantifying changes in liver fat in nonalcoholic fatty liver disease trials

Abstract

The magnetic resonance imaging–estimated proton density fat fraction (MRI-PDFF) is a novel imaging-based biomarker that allows fat mapping of the entire liver, whereas the magnetic resonance spectroscopy–measured proton density fat fraction (MRS-PDFF) provides a biochemical measure of liver fat in small regions of interest. Cross-sectional studies have shown that MRI-PDFF correlates with MRS-PDFF. The aim of this study was to show the utility of MRI-PDFF in assessing quantitative changes in liver fat through a three-way comparison of MRI-PDFF and MRS-PDFF with the liver histology–determined steatosis grade at two time points in patients with nonalcoholic fatty liver disease (NAFLD). Fifty patients with biopsy-proven NAFLD who participated in a randomized trial underwent a paired evaluation with liver biopsy, MRI-PDFF, and MRS-PDFF at the baseline and 24 weeks. The mean age and body mass index were 47.8 ± 11.7 years and 30.7 ± 6.5 kg/m2, respectively. MRI-PDFF showed a robust correlation with MRS-PDFF both at week 0 and at week 24 (r = 0.98, P < 0.0001 for both). Cross-sectionally, MRI-PDFF and MRS-PDFF increased with increases in the histology-determined steatosis grade both at week 0 and at week 24 (P < 0.05 for all). Longitudinally, patients who had a decrease (≥1%) or increase (≥1%) in MRI-PDFF (confirmed by MRS-PDFF) showed a parallel decrease or increase in their body weight and serum alanine aminotransferase and aspartate aminotransferase levels at week 24 (P < 0.05). This small increase or decrease in liver fat could not be quantified with histology. Conclusion In this longitudinal study, MRI-PDFF correlated well with MRS-PDFF and was more sensitive than the histology-determined steatosis grade in quantifying increases or decreases in the liver fat content. Therefore, it could be used to quantify changes in liver fat in future clinical trials.

Time to Replace Assessment of Liver Histology With MR-Based Imaging Tests to Assess Efficacy of Interventions for Nonalcoholic Fatty Liver Disease

“…For the majority of patients with NAFLD, early disease is characterised by development of excess liver lipid (containing intra-hepatic triglyceride) and liver triglyceride can be easily and accurately quantified by magnetic resonance-based imaging techniques. Indeed, the quantification of liver triglyceride with these imaging techniques correlates very well with hepatic steatosis identified by histology 16 . In addition, these imaging techniques are more sensitive than the histology-determined steatosis grade in quantifying increases or decreases in the liver fat content and also provide better results than histology when steatosis has not involved the liver in a uniform manner 16,17 .…”

“…Indeed, the quantification of liver triglyceride with these imaging techniques correlates very well with hepatic steatosis identified by histology 16 . In addition, these imaging techniques are more sensitive than the histology-determined steatosis grade in quantifying increases or decreases in the liver fat content and also provide better results than histology when steatosis has not involved the liver in a uniform manner 16,17 . Improving intra-hepatic triglyceride content assessed non-invasively by either the magnetic resonance spectroscopy-proton density fat fraction or the magnetic resonance imagingproton density fat fraction 16,17 , would allow a focus on the early stages of disease in NAFLD.…”

“…In addition, these imaging techniques are more sensitive than the histology-determined steatosis grade in quantifying increases or decreases in the liver fat content and also provide better results than histology when steatosis has not involved the liver in a uniform manner 16,17 . Improving intra-hepatic triglyceride content assessed non-invasively by either the magnetic resonance spectroscopy-proton density fat fraction or the magnetic resonance imagingproton density fat fraction 16,17 , would allow a focus on the early stages of disease in NAFLD. Such an approach has been used recently by us 18 and by other investigators 19,20 , and the use of magnetic resonance-based techniques would also consistently improve retention of participants within clinical trials.…”

947 Shared Genetic Effects Between Hepatic Steatosis and Fibrosis: A Prospective Twin Study

“…MRI-PDFF has been previously shown to be a highly precise, accurate, and reproducible noninvasive biomarker to quantify hepatic fat content. (25,26), correlates well with MR spectroscopy (r 2 =0.99, p<0.001) (22,23), and is superior to noninvasive imaging techniques such as ultrasound and computed tomography for measuring hepatic fat content (27) even in iron-overloaded livers that may coexist with NAFLD livers. (28) MRI-PDFF has also been shown to correlate well with histology from contemporaneous liver biopsies.…”

Imaging-Based Assessment of Steatosis, Inflammation and Fibrosis in NAFLD

“…MRI-PDFF has shown promise in longitudinal studies assessing changes in steatosis with treatment [30][31][32]. In the FLINT study, a randomized controlled trial (RCT) of obeticholic acid vs. placebo for 72 weeks, MRI-PDFF accurately differentiated steatosis S0-1 from S2-3 (AUROC 0.95) and S0-2 from S3 (AUROC 0.96) at baseline [33•].…”