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Review
. 2018 Aug;68(2):763-772.
doi: 10.1002/hep.29797.

Noninvasive, Quantitative Assessment of Liver Fat by MRI-PDFF as an Endpoint in NASH Trials

Cyrielle Caussy  1   2 , Scott B Reeder  3 , Claude B Sirlin  4 , Rohit Loomba  1   5   6
Affiliations
Review

Noninvasive, Quantitative Assessment of Liver Fat by MRI-PDFF as an Endpoint in NASH Trials

Cyrielle Caussy et al. Hepatology. 2018 Aug.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide, and the progressive form of this condition, nonalcoholic steatohepatitis (NASH), has become one of the leading indications for liver transplantation. Despite intensive investigations, there are currently no United States Food and Drug Administration-approved therapies for treating NASH. A major barrier for drug development in NASH is that treatment response assessment continues to require liver biopsy, which is invasive and interpreted subjectively. Therefore, there is a major unmet need for developing noninvasive, objective, and quantitative biomarkers for diagnosis and assessment of treatment response. Emerging data support the use of magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) as a noninvasive, quantitative, and accurate measure of liver fat content to assess treatment response in early-phase NASH trials. In this review, we discuss the role and utility, including potential sample size reduction, of MRI-PDFF as a quantitative and noninvasive imaging-based biomarker in early-phase NASH trials. Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide.() NAFLD can be broadly classified into two categories: nonalcoholic fatty liver, which has a minimal risk of progression to cirrhosis, and nonalcoholic steatohepatitis (NASH), the more progressive form of NAFLD, which has a significantly increased risk of progression to cirrhosis.() Over the past two decades, NASH-related cirrhosis has become the second leading indication for liver transplantation in the United States.() For these reasons, pharmacological therapy for NASH is needed urgently. Despite intensive investigations, there are currently no therapies for treating NASH that have been approved by the United States Food and Drug Administration.().

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Conflict of interest statement

Conflict of interests: Dr. Sirlin consults, advises, and is on the speakers’ bureau for Bayer. Drs. Loomba and Sirlin received grants from GE Healthcare and Siemens Inc. Dr. Reeder reports that the University of Wisconsin receives research support from GE Healthcare and Bracco Diagnostics. Dr. Reeder consults for Parexel International and is a founder of Calimetrix, LLC. Dr. Caussy reports no other conflict of interests.

Figures

Figure 1
Figure 1. Correlation between MRI-PDFF and percentage of hepatocytes with steatosis by histology
Correlation between MRI-PDFF and histologic steatosis grade classified by the percentage of hepatocyte with steatosis using (25) in individuals with biopsy-proven NAFLD (60).
Figure 2
Figure 2. MRI-PDFF assessment and quantification of hepatic steatosis
Example PDFF maps using complex MRI (C-MRI, left) and magnitude MRI (M-MRI, right) both show elevated PDFF in the liver (~32%). M-MRI is limited to a dynamic range of 0–50% unlike C-MRI which has a full dynamic range from 0–100%.
Figure 3
Figure 3. Longitudinal changes in MRI-PDFF after weight loss surgery
PDFF is shown in a patient before (pre-op) and after (post-op) weight loss surgery. Images from left to right represent PDFF before a very low caloric diet (pre-VLCD) pre-op and the longitudinal follow-up showing a decrease in PDFF.
See this image and copyright information in PMC

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