Ogawa, Yuji

ABSTRACT 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.

Abstract Background and Aims Despite that hepatic fibrosis often affects the liver globally, spatial distribution can be heterogeneous. This study aimed to investigate the effect of liver stiffness (LS) heterogeneity on concordance between MR elastography (MRE)‐based fibrosis staging and biopsy staging in patients with NAFLD. Approach and Results We retrospectively evaluated data from 155 NAFLD patients who underwent liver biopsy and 3 Tesla MRE and undertook a retrospective validation study of 169 NAFLD patients at three hepatology centers. Heterogeneity of stiffness was assessed by measuring the range between minimum and maximum MRE‐based LS measurement (LSM). Variability of LSM was defined as the stiffness range divided by the maximum stiffness value. The cohort was divided into two groups (homogenous or heterogeneous), according to whether variability was below or above the average for the training cohort. Based on histopathology and receiver operating characteristic (ROC) analysis, optimum LSM thresholds were determined for MRE‐based fibrosis staging of stage 4 (4.43, kPa; AUROC, 0.89) and stage ≥3 (3.93, kPa; AUROC, 0.89). In total, 53 had LSM above the threshold for stage 4. Within this group, 30 had a biopsy stage of <4. In 86.7% of these discordant cases, variability of LSM was classified as heterogeneous. In MRE‐based LSM stage ≥3, 88.9% of discordant cases were classified as heterogeneous. Results of the validation cohort were similar to those of the training cohort. Conclusions Discordance between biopsy‐ and MRE‐based fibrosis staging is associated with heterogeneity in LSM, as depicted with MRE.