Editorial: Refining the Natural History of MASLD by Imaging‐Based Markers: The GOLDMINE Study

In Alimentary Pharmacology & Therapeutics, Sharpton et al. [1] describe the protocol of a multicentric, prospective study of clinical outcomes by magnetic resonance imaging (MRI)-based markers in Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) – the GOLDMINE (Global Longitudinal Assessment of MASLD using Magnetic Resonance Elastography [MRE]) study. This project, coordinated by the University of California, San Diego, United States, involves international partners and is anticipated to enrol 1000 patients with MASLD followed up for 10 years. Notably, the full spectrum of MASLD will be included, ranging from simple steatosis to Metabolic dysfunction-Associated Steatohepatitis (MASH)-related cirrhosis. Adjudicated events will include progression to cirrhosis and clinically significant portal hypertension, liver decompensation, hepatocellular carcinoma, and liver-related death or transplantation, with competing events including cardiovascular outcomes and non-liver-related mortality. This study offers a unique opportunity to explore the natural history of biopsy-proven MASLD across different ethnicities, risk factors, and undergoing current or future MASH-related drug therapy. Additionally, this exploration will be performed in a real-world context, exploiting MRI-based tools, which are the most accurate non-invasive tests (NITs) for fibrosis staging in MASLD as well as promising tools for prognostication. In a global context of NIT implementation and increasing accessibility to drug treatment by regulation agencies, this cohort will provide physicians with useful information in a contemporary setting. Over the last years, increasing evidence has acknowledged the role of MRE for disease monitoring and outcome prediction in MASLD (Table 1), but the evidence is so far limited by heterogeneity in study populations and follow up of observation. 4.39 kPa MRE cut-off to identify cirrhosis (AUC 0.92) 6.48 kPa MRE cut-off to predict decompensation (AUC 0.71) Progressively higher odds of decompensation along with MRE-stiffness values Gidener et al. [3] 829 MASLD subjects (639 without cirrhosis, 194 with compensated cirrhosis) Baseline LSM predictive of future cirrhosis development (age-adjusted HR 2.93; 95% CI 1.86–4.62; p < 0.0001) Baseline LSM predictive of future decompensation per 1 kPa increment (HR 1.32; 95% CI 1.13–1.56; p = 0.0007) In MASLD patients without cirrhosis, progressive MRE-LSM was associated with 7-fold increase of incident cirrhosis (p = 0.059) In MASH-related cirrhosis, progressive LSM values led to decompensation or death in 100% of cases (p 0.001) Baseline MRE-LSM values were significantly associated with liver decompensation, HCC, and overall mortality Progressors (delta LSM ≥ 19%) had significantly higher HRs for decompensated cirrhosis, HCC, and liver-related events Progressive MRE-LSM values associated with cirrhosis (60.1 HR) and liver-related events, even for low baseline values (stages 0–2 fibrosis) In GOLDMINE, a histological comparison with MRI/MRE (all centrally read) will provide evidence of the accuracy of MRI/MRE for either fibrosis staging or outcome prediction, expanding the imaging-based NIT allocation, similarly to what has been previously shown for vibration-controlled transient elastography [9]. Furthermore, the 2- and 4-year repetition of MRI/MRE will help integrate (1) metabolic phenotype, (2) prevalent and incident co-morbidities, (3) MASH-related drug treatment (e.g., resmetirom and semaglutide), (4) ethnic and anthropometric features, (5) gene variant susceptibility (e.g., PNPLA3 polymorphisms), with clinical outcomes across changes in NITs. This aspect is of utmost relevance, and currently the cornerstone of eligibility assessment to drug treatment as well as treatment response (utility versus futility) in a population-based, biopsy-free environment [10]. Further, the joint collection of serum/plasma for biobanking will support the analysis/validation of fibrogenesis markers as well as omics platforming for a joint dry/liquid picture of disease activity across time, with potentially a better understanding of the factors leading to accelerated versus decelerated progression to cirrhosis and more advanced stages liver disease towards decompensation. MASLD displays an extraordinary variability in phenotypes and disease progression, as part of a complex spectrum inside the systemic inflammation driven by metabolic syndrome. The monitoring of fibrosis progression, the identification of key drivers of liver damage at the individual level, and patient selection of specific treatments as well as for interdisciplinary management are only a few of the unmet needs that MASLD still currently bears. By developing this protocol study, Sharpton and Colleagues have established a robust basis for addressing these needs, with relevant benefits and advances in knowledge. Federico Perna: writing – original draft, data curation. Angelo Armandi: conceptualization, writing – original draft, writing – review and editing, data curation, supervision. The authors have nothing to report. This article is linked to Sharpton et al. paper. To view this article, https://doi.org/10.1111/apt.70696. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.