The Effect of Multi-Parametric Magnetic Resonance Imaging in Standard of Care for Nonalcoholic Fatty Liver Disease: Protocol for a Randomized Control Trial

Abstract

Background The rising prevalence of nonalcoholic fatty liver disease (NAFLD) and the more aggressive subtype, nonalcoholic steatohepatitis (NASH), is a global public health concern. Left untreated, NAFLD/NASH can lead to cirrhosis, liver failure, and death. The current standard for diagnosing and staging liver disease is a liver biopsy, which is costly, invasive, and carries risk for the patient. Therefore, there is a growing need for a reliable, feasible, and cost-effective, noninvasive diagnostic tool for these conditions. LiverMultiScan is one such promising tool that uses multi-parametric magnetic resonance imaging (mpMRI) to characterize liver tissue and to aid in the diagnosis and monitoring of liver diseases of various etiologies. Objective The primary objective of this trial (RADIcAL1) is to evaluate the cost-effectiveness of the introduction of LiverMultiScan as a standardized diagnostic test for liver disease in comparison to standard care for NAFLD, in different EU territories. Methods RADIcAL1 is a multi-center randomized control trial with 2 arms conducted in 4 European territories (13 sites, from across Germany, Netherlands, Portugal, and the United Kingdom). In total, 1072 adult patients with suspected fatty liver disease will be randomized to be treated according to the result of the mpMRI in the intervention arm, so that further diagnostic evaluation is recommended only when values for metrics of liver fat or fibro-inflammation are elevated. Patients in the control arm will be treated as per center guidelines for standard of care. The primary outcome for this trial is to compare the difference in the proportion of patients with suspected NAFLD incurring liver-related hospital consultations or liver biopsies between the study arms, from the date of randomization to the end of the study follow-up. Secondary outcomes include patient feedback from a patient satisfaction questionnaire, at baseline and all follow-up visits to the end of the study, and time, from randomization to diagnosis by the physician, as recorded at the final follow-up visit. Results This trial is currently open for recruitment. The anticipated completion date for the study is December 2020. Conclusions This randomized controlled trial will provide the evidence to accelerate decision making regarding the inclusion of mpMRI-based tools in existing NAFLD/NASH clinical care. RADIcAL1 is among the first and largest European health economic studies of imaging technologies for fatty liver disease. Strengths of the trial include a high-quality research design and an in-depth assessment of the implementation of the cost-effectiveness of the mpMRI diagnostic. If effective, the trial may highlight the health economic burden on tertiary-referral hepatology clinics imposed by unnecessary consultations and invasive diagnostic investigations, and demonstrate that including LiverMultiScan as a NAFLD diagnostic test may be cost-effective compared to liver-related hospital consultations or liver biopsies. Trial Registration ClinicalTrials.gov NCT03289897 https://clinicaltrials.gov/ct2/show/NCT03289897 International Registered Report Identifier (IRRID) DERR1-10.2196/19189

Clinical Utility of Magnetic Resonance Imaging Biomarkers for Identifying Nonalcoholic Steatohepatitis Patients at High Risk of Progression: A Multicenter Pooled Data and Meta-Analysis

“…The diagnostic performance of cT1 for separating NAFLD from NASH in this study showed good sensitivity and specificity at a cT1 cut-off value of 800ms. This result further justifies the use of a previously defined cut-off value of cT1 ≥ 800ms, below which no further diagnostic evaluation is warranted [39,40] . The healthy participants from the UK biobank imaging study had a cT1 range of between 619-755ms suggesting that 800ms can be considered as the upper limit of normal for cT1.…”

“…Biomarker performance for discriminating those with NASH from simple NAFLD was assessed using a cutoff of cT1≥800ms, MRI liver fat ≥5% or a combination of both. These cut-off values have been described previously as indicators for recommending further diagnostic evaluation [39,40] . Using the cut-off of cT1≥800ms to discriminate those with NASH resulted in a sensitivity of 75%, specificity of 66% and PPV and NPV both of 71%.…”

Simultaneous T2 and mapping of multiple sclerosis lesions with radial RARE‐EPI

“…The potential of the proposed 2in1‐RARE‐EPI hybrid is not limited to MS lesions or even brain imaging. 2in1‐RARE‐EPI offers the capacity for simultaneous T 2 and mapping in applications dealing with bulk or physiological motion, such as cardiac imaging including myocardial T 2 and mapping, 102‐104 as well as multi‐parametric MRI of the eye, kidney, abdomen, and liver 105‐110 . For these applications in moving organs, motion correction approaches such as 1D or 2D linear phase correction promise to ensure immunity to bulk motion 111,112 .…”

“…2in1-RARE-EPI offers the capacity for simultaneous T 2 and T * 2 mapping in applications dealing with bulk or physiological motion, such as cardiac imaging including myocardial T 2 and T * 2 mapping, [102][103][104] as well as multi-parametric MRI of the eye, kidney, abdomen, and liver. [105][106][107][108][109][110] For these applications in moving organs, motion correction approaches such as 1D or 2D linear phase correction promise to ensure immunity to bulk motion. 111,112 The use of radial k-space trajectories shown in the current study holds the promise to render additional navigator data unnecessary because the densely sampled k-space center can be deployed for phase correction of motion corrupted data.…”

Aspirin for Metabolic Dysfunction–Associated Steatotic Liver Disease Without Cirrhosis

“…[20][21][22][23] While no MCID was prespecified, prior studies support a relative reduction in hepatic fat of 30% or greater as clinically meaningful because that degree of change was associated with histological improvements in steatohepatitis [20][21][22][23] and fibrosis. 26 Prespecified nonkey secondary end points consisted of 6-month absolute changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), iron-corrected T 1 score, a validated composite MRI estimate of hepatic inflammation and fibrosis, 18,[27][28][29] VCTE-estimated liver fibrosis, body weight, and body mass index (calculated as weight in kilograms divided by height in meters squared). No MCID was prespecified for nonkey secondary outcomes.…”