Utility and cost-effectiveness of LiverMultiScan for MASLD diagnosis: a real-world multi-national randomised clinical trial

Abstract

Background: Increasing prevalence of metabolic dysfunction-associated liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) poses a growing healthcare burden. Noninvasive diagnostic tools to replace liver biopsy are urgently needed. We investigated the utility and cost-effectiveness of including multiparametric magnetic resonance imaging (mpMRI) to the management of adults with suspected MASLD multi-nationally.

Methods: RADIcAL-1, a 1:1 randomised controlled trial (standard-of-care [SoC] vs. imaging arm [IA; SoC+mpMRI]) included 802 participants from Germany, Netherlands, Portugal and UK. Wilcoxon-rank tests were used to compare access to healthcare practitioners, patient assessments and proportion of patients with a diagnosis (%diagnosis). Liver fat and disease activity (corrected T1 [cT1]) were used to identify patients not requiring biopsy in the imaging arm. Primary endpoint was mpMRI cost-effectiveness and improvement in resource use (visits avoided) using mpMRI.

Results: mpMRI is cost-effective with an ICER of €4968/QALY gained. 403 were randomised to IA and 399 to SoC. SoC has significantly more specialist appointments (p = 0.015) and patient assessments (p < 0.001). Across all involved hospitals, %diagnosis is significantly higher in the imaging arm (p = 0.0012). cT1 correctly classifies 50% of patients without MASH with fibrosis and can avoid biopsy. Including all costs, the imaging arm incurs higher short-term per-patient healthcare expenditure compared to the SoC arm (€1,300 vs. €830).

Conclusion: Adding mpMRI to SoC for the management of adults with suspected MASLD multi-nationally is cost-effective, enhances rate of diagnosis multi-nationally and increases rate of diagnosis without increasing other liver-related health care resource use. Due to the need for standardisation of SoC, widespread use can support optimisation of the MASLD clinical pathway and improve long-term patient management.

Fig. 1. Summary of study visits for all participants and the RADIcAL1 trial profile including a case study for two female patients with suspected MASLD.

Summary of study visits for (a) all participants and (b) RADIcAL1 trial profile. Also shown in (a) is the proportion of patients who received a biopsy following clinician discretion but did not have Metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis (MAS < 4 and fibrosis <2), and those who received a final diagnosis in both the standard-of-care (SoC) and imaging arms, and (b) the study visits for only those randomised into the imaging arm (SoC + mpMRI), the proportion of patients classified as high risk using mpMRI (PDFF ≥ 10% or cT1 ≥ 800 ms), those who received a liver biopsy and those with cT1 < 875 ms who could have avoided a liver biopsy to assess for MASH with fibrosis. (c) cT1 and PDFF maps for two female patients with suspected Metabolic dysfunction–associated steatotic liver disease (MASLD), both with BMI 33, no diabetes, with elevated liver enzymes (ALT and AST) who underwent liver biopsy following clinician discretion to confirm diagnosis. Arrows indicate elevated biochemical markers (above the upper limit of normal) and histological stage. In the cT1 maps, lower values (cooler colours) represent areas with lower cT1 values, and therefore, lower disease activity, whereas higher cT1 values (warmer colours) represent areas of the liver with higher disease activity. In the PDFF maps, darker shades represent lower liver fat, whilst lighter shades represent higher liver fat. BMI body mass index, ALT alanine aminotransferase, AST aspartate aminotransferase; cT1 corrected T1, PDFF proton density fat fraction, mpMRI multiparametric MRI.

Fig. 2. Proportion of patients in the imaging and standard-of-care arms who received a final diagnosis by the end of the trial, along with the total number of healthcare visits, patient assessments, and associated costs in the standard-of-care management for both arms.

a Proportion of patients in the imaging and standard-of-care (SoC) arms (total/whole cohort and regional) who received a certain diagnosis by the end of the trial period. Aggregate (b) number of visits with health care practitioners (general practitioner, specialist outside hospital visit, specialist at hospital visit and therapist) and patient assessments (blood tests, biopsy and ultrasound testing) between the imaging arm (SoC + multiparametric MRI) and standard of care arms, and (c) costs incurred in the standard of care management of patients in the imaging arm (without inclusion of MRI costs) and the SoC arm. All significantly different comparisons between the imaging and SoC arms are denoted with the following levels of significance: *p < 0.05; **p < 0.01; ***p < 0.001. There were N = 802 participants in the whole study, N = 403 imaging arm (Germany: 107, Netherlands: 89, Portugal: 79, UK:128), and N = 399 in the SoC arm (Germany: 109, Netherlands: 88, Portugal: 75, UK: 127).