Marked difference in liver fat measured by histology vs. magnetic resonance-proton density fat fraction: A meta-analysis
S. U. Qadri, Emilia Vartiainen, Mari Lahelma, Kimmo Porthan, An Tang, Ilkay S. Idılman, Jurgen H. Runge, Anne Juuti, Anne Penttilä, Juhani Dabek, Tiina E. Lehtimäki, Wenla Seppänen, Johanna Arola, Perttu Arkkila, Jaap Stoker, Muşturay Karçaaltıncaba, Michael Pavlides, Rohit Loomba, Claude B. Sirlin, Taru Tukiainen, Hannele Yki‐Järvinen
Abstract
Background & Aims: Pathologists quantify liver steatosis as the fraction of lipid droplet-containing hepatocytes out of all hepatocytes, whereas the magnetic resonance-determined proton density fat fraction (PDFF) reflects the tissue triacylglycerol concentration. We investigated the linearity, agreement, and correspondence thresholds between histological steatosis and PDFF across the full clinical spectrum of liver fat content associated with non-alcoholic fatty liver disease. Methods: Using individual patient-level measurements, we conducted a systematic review and meta-analysis of studies comparing histological steatosis with PDFF determined by magnetic resonance spectroscopy or imaging in adults with suspected non-alcoholic fatty liver disease. Linearity was assessed by meta-analysis of correlation coefficients and by linear mixed modelling of pooled data, agreement by Bland-Altman analysis, and thresholds by receiver operating characteristic analysis. To explain observed differences between the methods, we used RNA-seq to determine the fraction of hepatocytes in human liver biopsies. Results: histology. Conclusions: Histological steatosis and PDFF have non-perfect linearity and fundamentally different scales of measurement. Liver fat values obtained using these methods may be rendered comparable by conversion equations or threshold values. Impact and implications: Magnetic resonance-proton density fat fraction (PDFF) is increasingly being used to measure liver fat in place of the invasive liver biopsy. Understanding the relationship between PDFF and histological steatosis fraction is important for preventing misjudgement of clinical status or treatment effects in patient care. Our analysis revealed that histological steatosis fraction is often significantly higher than PDFF, and their association varies across the spectrum of fatty liver severity. These findings are particularly important for physicians and clinical researchers, who may use these data to interpret PDFF measurements in the context of histologically evaluated liver fat content.