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

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..

Liraglutide, Sitagliptin, and Insulin Glargine Added to Metformin: The Effect on Body Weight and Intrahepatic Lipid in Patients With Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease

“…Additionally, MRI rather than liver biopsy as the reference standard to measure IHL was used. In general, histological data is the golden standard for liver disease research, and MRI is recommended by guidelines to be adopted in clinical trials for its noninvasive advantage and high‐quality diagnostic performance …”

“…At baseline (2 weeks after screening), eligible patients underwent abdominal magnetic resonance imaging (MRI) (GE Discovery 750 3.0T MR) to assess visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) in participant centers. IHL were assessed using MRI‐PDFF, accurately measured by MRI iterative decomposition of water and fat with echo asymmetry and least‐squares estimation (IDEAL IQ) (GE Discovery 750 3.0T MR), as a surrogate biomarker owing to its practicality, reliability, and transferability . Whole liver was covered during axial IDEAL IQ examination.…”

Systematic Review: Noninvasive Assessments of Intestinal Failure–Associated Liver Disease in the Adult Population

“…However, so far 1H‐MRS and MRI‐PDFF have not been validated in the CIF population, yet these 2 modalities are considered as the most accurate ways to noninvasively assess liver steatosis, including the NAFLD/NASH population across patient subgroups and disease states . It was recently suggested to use these modalities to assess treatment response in the early‐phase NASH trials instead of liver biopsy . However, because of the equipment and costs associated with MR technology, along with the technical expertise required to perform and process the readings, more readily available tools to noninvasively quantify steatosis are desirable as a point‐of‐care test during an outpatient clinic visit.…”

Ad Libitum Mediterranean and Low‐Fat Diets Both Significantly Reduce Hepatic Steatosis: A Randomized Controlled Trial

“…Hepatic triglyceride content (HTGC) was quantified by MRS/proton density fat fraction (MRS‐PDFF) using a two‐voxel point‐resolved spectroscopy sequence performed on a Philips 3T Ingenia scanner (Philips Medical Systems, Best, The Netherlands). PDFF methods are recommended to assess treatment efficacy for clinical trials in NAFLD . For each patient, an e‐THRIVE sequence was run before the MRS sequence to obtain sagittal, coronal, and axial slices through the entire liver in order to position the volume of interest away from tissue boundaries, major blood vessels, or intrahepatic bile ducts.…”