Suzanne Sharpton

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.

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LINKED CONTENT: This article is linked to Cheung et al papers. To view these articles, visithttps://doi.org/10.1111/apt.17722andhttps://doi.org/10.1111/apt.17774

LINKED CONTENT: This article is linked to Sharpton et al papers. To view these articles, visit https://doi.org/10.1111/apt.17384 and https://doi.org/10.1111/apt.17447

Summary: Background and Aims: Whether hepatocellular carcinoma (HCC) increases the familial risk for hepatic fibrosis has not been thoroughly explored, particularly in Mexican Americans who are disproportionately affected by obesity and metabolic syndrome. We evaluated the risk of significant hepatic fibrosis in first‐degree relatives of Mexican American adults with HCC.Methods: We performed a cross‐sectional analysis of a prospective cohort of Mexican American probands with HCC and first‐degree relatives enrolled in the Hispanic Liver Cancer Cohort study. We evaluated the prevalence of hepatic fibrosis in first‐degree relatives, defined by liver stiffness measurement (LSM) >= 7.0 kPa with transient elastography (TE). Secondary outcomes included the prevalence of definite hepatic steatosis, defined by controlled attenuation parameter >=288 dB/m.Results: We identified 70 probands diagnosed with HCC; 47% were female and the mean age was 62 years (±13 years). Among 112 first‐degree relatives with a mean age of 43 years (±14 years), 19 (17%) had significant fibrosis and 47 (42%) had definite hepatic steatosis, respectively. The prevalence of significant fibrosis was 20% in first‐degree relatives 40 years of age or older. Regression analysis revealed that diabetes (OR 3.2, 95% CI: 1.1–9.2, p = 0.03) and aspartate aminotransferase >=30 units/L (OR 4.0, 95% CI: 1.4–11.7, p = 0.01) were predictors of significant fibrosis in first‐degree relatives.Conclusions: Using a well‐phenotyped familial cohort, we found that the prevalence of significant fibrosis and definite hepatic steatosis are high in first‐degree relatives of Mexican Americans with HCC, particularly those with diabetes, suggesting that this population may benefit from screening for liver disease.

Statins, the most widely used lipid-lowering drugs, are increasingly recognized to have pleiotropic effects including anti-inflammatory and antiangiogenic properties as well as effects on fibrogenesis and liver endothelial function. Given these pathophysiological effects, there is a growing interest in clinical use of statins in persons with cirrhosis. In this review, we summarize available data regarding the safety, adverse effects, and pharmacokinetics of statins in cirrhosis. We review clinical evidence, derived primarily from retrospective cohort and population-based studies, on the association between statin use and reduction in risk for hepatic decompensation and mortality in persons with established cirrhosis. We also review evidence to date regarding the effects of statins on portal hypertension and in chemoprevention of HCC. Finally, we highlight ongoing prospective randomized controlled trials that we expect will expand our understanding of the safety, pharmacokinetics, and efficacy of statins in cirrhosis and guide clinical practice.