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Proton density fat fraction accurately classifies hepatic changes in NASH

Proton density fat fraction, or PDFF, estimated by magnetic resonance imaging scanners of different field strength and at different sites accurately classified changes in hepatic steatosis compared with histologic analysis of biopsies, according to a recently published study.

“We found that PDFF correlates well with histologic hepatic steatosis grade cross-sectionally, and that change in PDFF correlates well with change in histologic hepatic steatosis grade longitudinally,” Michael S. Middleton, MD, PhD, from the University of California, San Diego, and colleagues wrote. “Although we did not perform a direct comparison of [controlled attenuation parameter (CAP)] and PDFF, the accuracy of MRI to estimate PDFF has been reported to be higher than that of CAP, using histology as reference standard.”

To assess the diagnostic performance of PDFF to grade hepatic steatosis, the researchers enrolled 283 adults from the Farnesoid X Receptor Ligand Obeticholic Acid in NASH Treatment (FLINT) trial. Of those enrolled, 113 had MRI and liver biopsy at baseline, 85 had MRI and liver biopsy at end of treatment, and 78 had MRI and liver biopsy at both time points.

After controlling for other histologic features, the researchers found that PDFF correlated significantly with steatosis (Pearson Partial Correlation < 0.8; 95% CI, 0.73-0.86) and with change in histologic steatosis grade (Pearson Partial Correlation < 0.63; 95% CI, 0.47-0.75).

As a surrogate, PDFF measurement by MRI showed high agreement with biopsies as reference for steatosis grade 0 to 1 (area under receiving operating curve = 0.95; 95% CI, 0.91-0.98) and grade 0 to 2 vs. 3 (AUROC = 0.96; 95% CI, 0.93-0.99). The cut-off values for discrimination at 90% specificity were16.3% for grades 2 to 3 and 21.7% for grade 3.

At the end of treatment, PDFF classification of histologic hepatic steatosis grade improvement (AUROC = 0.81; 95 CI, 0.71-0.91) and worsening (AUROC = 0.81; 95% CI, 0.63-0.99) was inferior to baseline measurements but still showed high agreement with biopsies. At the end of treatment, cut-off values for change at 90% specificity were –5.1% for improvement and 5.6% for worsening.

“As emphasized previously by others, PDFF is a quantitative marker of MRI-visible fat content while histology scoring is a semi-quantitative marker of proportion of steatotic hepatocytes. Because PDFF and histology do not attempt to measure the same quantity, perfect agreement is not expected,” the researchers concluded. “Importantly, change in PDFF accurately classified change in [end-of-treatment] histologic hepatic steatosis grade. These findings support wider use of PDFF in multi-center trials in adults as a biomarker for hepatic steatosis at baseline, and for change in hepatic steatosis with treatment.” – by Talitha Bennett

Disclosure: Middleton reports has contracted work or discussion for contracted work with Alexion, AstraZeneca, Bioclinica, Biomedical Systems, Bristol-Myers Squibb, Celgene, Galmed, Genentech, General Electric, Genzyme, Gilead, Icon Pharmaceuticals, Isis, Janssen, NuSirt, Perspectum, Pfizer, Profil, Sanofi, Shire, Siemens, Synageva, Takeda, Virtualscopics and Zydus; is a stockholder with General Electric and Pfizer; and received grants from General Electric, Gilead and Guerbet. Please see the full study for the other researchers’ relevant financial disclosures.