Suzanne R. Sharpton, Luis Antonio Diaz, Kay Pepin, Maral Amangurbanova, Egbert Madamba, Ricki Bettencourt, Seema Singh, Mark A. Valasek, Mary Dalupang, Kaleb Tesfai, Michael S. Middleton, C Behling, Winston Dunn, Atsushi Nakajima, Kento Imajo, Yuji Ogawa, Cyrielle Caussy, Dina Halegoua‐DeMarzio, Arpan Mohanty, Daniel Q. Huang, Michael Fuchs, Bilal Hameed, Jonathan G. Stine, Maya Balakrishnan, Meagan Gray, Manuel Rodriguez, Andre DeLeon, Rohit Puskoor, Raj Vuppalanchi, Jaideep Behari, Lars Hansen, Cynthia Miller, Valentina Medici, Souvik Sarkar, Jerome Boursier, Monica A. Tincopa, Veeral Ajmera, Lisa Richards, Claude B. Sirlin, Richard L. Ehman, Rohit Loomba
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) exhibits marked heterogeneity in fibrosis progression and liver-related outcomes. Liver biopsy is not feasible for longitudinal risk stratification at scale, creating a need for validated non-invasive biomarkers, particularly imaging biomarkers, that can predict clinically meaningful disease progression and liver-related outcomes. AIMS: To describe the design and rationale of the GOLDMINE study, established to determine whether non-invasive imaging biomarkers predict MASLD progression and liver-related clinical outcomes. METHODS: GOLDMINE is an investigator-initiated, multi-centre, international longitudinal cohort enrolling up to 1000 adults with either biopsy-proven MASLD or MASLD cirrhosis across the full fibrosis spectrum. Participants are recruited from 15 sites in the US and 4 international sites (Japan, Singapore and France). At baseline, participants undergo clinical phenotyping, vibration-controlled transient elastography, and advanced magnetic resonance imaging (MRI), including proton-density-fat-fraction and magnetic resonance elastography (MRE). MRI (and biospecimen banking) is repeated at 2-year intervals (years 2 and 4), with annual follow-up visits for up to 10 years. Baseline liver histology is centrally processed, digitized and reviewed by a single expert hepatopathologist; all MRI/MREs are centrally interpreted. RESULTS: The prespecified clinical outcomes include progression to cirrhosis, clinically significant portal hypertension, major adverse liver-related outcomes (ascites, hepatic encephalopathy, portal hypertensive bleeding, liver transplantation/qualification), hepatocellular carcinoma, major adverse cardiovascular events, and all-cause mortality, with independent central adjudication of all events. CONCLUSIONS: GOLDMINE establishes a rigorously phenotyped MASLD cohort integrating centralized histology, advanced MRI-based biomarkers, longitudinal biobanking, and adjudicated outcomes, providing a platform to validate imaging and blood-based prognostic biomarkers in MASLD.