The escalating prevalence of liver diseases globally has long posed challenges for healthcare providers, predominantly due to the silent progression of conditions like liver cirrhosis and hepatocellular carcinoma until they reach advanced stages. Traditional detection methods have been neither affordable nor sufficiently prompt, often relegating diagnoses to later stages when treatment options are limited and prognoses poor. Addressing this critical gap, the team led by Rickard Strandberg and Hannes Hagström developed the CORE model incorporating routine biochemical markers to stratify risk efficiently.

The CORE risk score is fundamentally built on five key variables: demographic factors—age and sex—and biochemical readings of three liver-specific enzymes measured routinely during standard health evaluations: aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). These enzymes are biomarkers reflective of hepatocellular injury and cholestasis, central to liver function and indicative of underlying pathology when elevated. By integrating these parameters through sophisticated statistical modeling, the researchers crafted a robust predictive algorithm tailored for use in general populations.

At the heart of this innovation is the intent to facilitate early detection within primary healthcare frameworks. To this end, the team has made available an intuitive web-based calculator, accessible through www.core-model.com, designed for healthcare professionals to rapidly estimate a patient’s 10-year risk of developing severe liver disease. This digital tool stands to empower practitioners with an evidence-based method that complements conventional diagnostics, thus enabling proactive management and timely referrals.

The CORE model’s development drew upon longitudinal data encompassing over 480,000 individuals from Stockholm who underwent routine health assessments between 1985 and 1996. The extensive follow-up period of up to three decades allowed for a comprehensive evaluation of the model’s predictive capacity, revealing that approximately 1.5% of the population progressed to advanced liver disease or required liver transplantation within the monitored timeframe. Such a vast dataset underscored the model’s reliability and potential for widespread applicability.

Comparatively, the CORE risk score demonstrated superior predictive performance to existing tools, notably outperforming the widely used FIB-4 index. While FIB-4, which also incorporates liver enzymes and platelet counts, has been employed as a fibrosis marker, its efficacy for forecast risk in unselected populations has been limited. The CORE model’s capacity to distinguish at-risk individuals with an accuracy rate of 88% marks a significant leap forward, addressing prior limitations and reinforcing its clinical utility.

To validate these findings beyond the Swedish cohort, external validation studies were conducted across population samples in Finland and the United Kingdom. The model retained high predictive accuracy within these varied demographics, attesting to the robustness and adaptability of the CORE score across different healthcare contexts and ethnic backgrounds. However, further investigation is warranted in specific subgroups known to be at elevated risk, such as individuals with type 2 diabetes mellitus or obesity, to tailor the model’s precision in these vulnerable populations.

In the broader context of therapeutic advancements, this early risk stratification approach aligns with emerging pharmacological interventions targeting liver fibrosis and carcinogenesis. The availability of drug treatments capable of arresting or reversing liver damage is an evolving landscape, and timely identification of candidates through CORE facilitates optimal treatment initiation. Such integration of predictive diagnostics with targeted therapies could shift the paradigm from reactive to preventive hepatology.

Moreover, for the CORE model to achieve maximal impact in routine clinical practice, seamless integration with electronic health record (EHR) systems remains a crucial step. Automation of risk score calculations during standard blood test reviews would alleviate the burden on clinicians and improve adherence to screening recommendations. Efforts toward embedding this tool within digital health infrastructures are anticipated to enhance clinical workflow and patient outcomes.

The collaboration underpinning this research unitizes expertise from institutions in Sweden and Finland, including Karolinska Institutet, Helsinki University Hospital, Helsinki University, and the Finnish Institute for Health and Welfare. Financial support from the Swedish Research Council, Region Stockholm’s CIMED initiative, and the Swedish Cancer Society facilitated this high-impact study. Notably, the lead investigators maintain transparency regarding potential conflicts of interest, with no direct pharmaceutical ties influencing the present work.

This major scientific milestone holds promise not only for reducing the morbidity and mortality associated with advanced liver diseases but also for alleviating the economic burden on healthcare systems through earlier interventions. As the global health community grapples with liver disease epidemics fueled by metabolic and viral etiologies, innovations like CORE represent a beacon of hope toward effective preventive care.

Looking ahead, the adoption of the CORE risk score in primary care protocols could transform liver disease management paradigms. Coupled with public health initiatives promoting liver health awareness and lifestyle modifications, this diagnostic advancement underscores the importance of integrating precision medicine principles into everyday clinical practice, ultimately improving patient prognoses and quality of life.

Subject of Research: People

Article Title: Use of new CORE risk score to predict 10 year risk of liver cirrhosis in general population: population-based cohort study

News Publication Date: 29-Sep-2025

Web References:
www.core-model.com
https://doi.org/10.1136/bmj-2024-083182

References:
Strandberg R, Åberg F, Asteljoki JV, et al. Use of new CORE risk score to predict 10 year risk of liver cirrhosis in general population: population based cohort study. The BMJ. 2025;doi:10.1136/bmj-2024-083182.

Keywords: Health and medicine; Liver; Liver cancer; Gastroenterology; Medical diagnosis; Fatty liver disease; Metabolic disorders

Clinically, MASLD is closely associated with five prominent cardiometabolic conditions: obesity, Type 2 diabetes or pre-diabetes, high blood pressure, elevated blood sugar levels, and low high-density lipoprotein (HDL) cholesterol. These risk factors are collectively recognized as cardiometabolic because they impact the cardiovascular system or disrupt metabolic processes critical for maintaining homeostasis. The intricate interplay of these factors contributes to the pathogenesis of MASLD, complicating disease progression and patient outcomes.

Despite the recognized burden of MASLD, there has been limited investigation into which of these cardiometabolic risk factors most significantly influence mortality rates among affected individuals. Addressing this crucial gap, researchers at Keck Medicine of USC conducted a comprehensive epidemiological study utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning three decades (1988–2018). This extensive dataset allowed the team to dissect mortality risks linked to individual cardiometabolic variables among more than 21,000 MASLD patients identified within a cohort exceeding 130,000 participants aged 20 years and older.

Their investigation revealed illuminating insights: among the cardiometabolic risk factors studied, three stood out as having the greatest association with increased mortality in MASLD patients. High blood pressure topped the list, followed by pre-diabetes or Type 2 diabetes, and then low HDL cholesterol levels. Specifically, high blood pressure elevated the risk of death by approximately 40%, pre-diabetes and Type 2 diabetes by 25%, and low HDL cholesterol by 15%. These associations held true irrespective of patients’ gender, sex, race, or ethnicity, underscoring the universal impact of these factors.

The prominence of hypertension as the most lethal cardiometabolic factor in MASLD challenges prevailing clinical assumptions. Prior to this study, Type 2 diabetes was often perceived as the predominant driver of mortality risk in liver disease patients. Matthew Dukewich, MD, PharmD, MS, a transplant hepatology fellow at USC and the study’s lead author, highlighted this paradigm shift: “This finding disrupts conventional thinking and suggests clinicians might need to re-evaluate how aggressively they manage blood pressure in the MASLD population.”

Additionally, obesity, despite being the most commonly observed risk factor in MASLD patients, demonstrated a nuanced relationship with mortality risk. The study’s analysis utilized body mass index (BMI) as an indicator of relative adiposity. Results indicated a positive correlation between BMI and mortality, with heavier patients facing higher risks of death. This gradient effect suggests a dose-dependent influence of obesity on disease progression and survival outcomes.

Importantly, the investigation also quantified the cumulative impact of multiple cardiometabolic risk factors on MASLD mortality. The presence of additional factors compounded mortality risk, with each extra cardiometabolic condition increasing the hazard of death by 15%. This cumulative risk underscores the multifactorial nature of MASLD and highlights the necessity for multifaceted therapeutic strategies aimed at comprehensive cardiometabolic control rather than isolated risk reduction.

Methodologically, the study benefited from the robustness of NHANES, a highly representative survey that integrates detailed health metrics, laboratory analyses, and long-term mortality data. By leveraging this rich resource, researchers could control for a wide spectrum of confounding factors and ensure broad generalizability of the findings across diverse U.S. populations. The longitudinal design further enabled evaluation of long-term outcomes linked to baseline cardiometabolic profiles.

Looking forward, the authors advocate for expanded research to deepen understanding of MASLD pathophysiology and its interrelations with genetic predispositions, lifestyle variables such as diet, and alcohol consumption patterns. They emphasize that unraveling these complex interactions could facilitate the development of precision medicine approaches, enabling clinicians to stratify patients based on risk profiles and tailor interventions accordingly.

Norah A. Terrault, MD, senior author of the study and hepatologist at Keck Medicine, reiterated the clinical import: “MASLD is a heterogenous, multifaceted disease. Identifying which cardiometabolic factors drive the highest mortality risk allows us to focus clinical efforts on modifiable targets, potentially improving patient prognosis substantially.” Her remarks underscore the translational potential of this epidemiological work in shaping future standards of care.

This study, published in Clinical Gastroenterology and Hepatology, marks a significant advance in MASLD research by clarifying the relative lethality of cardiometabolic complications within this patient group. It offers novel insights that challenge existing dogma about diabetes dominance in this space, drawing necessary attention to hypertension and cholesterol abnormalities. As MASLD prevalence continues to escalate in tandem with rising rates of obesity and metabolic syndrome worldwide, these findings bear critical implications for public health strategies, clinical management, and resource prioritization.

Ultimately, the study’s evidence advocates for an integrated approach to MASLD treatment—one that rigorously addresses blood pressure control, diabetes management, lipid optimization, and weight regulation simultaneously. By doing so, clinicians may arrest disease progression, reduce comorbid burden, and improve survival outcomes in this increasingly common and challenging chronic liver disease.

Subject of Research: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its cardiometabolic risk factors linked to mortality.
Article Title: Not provided explicitly in the content.
News Publication Date: Not specified in the content.
Web References:

• Study DOI: 10.1016/j.cgh.2025.09.003
• Keck Medicine of USC Liver Health Center: https://www.keckmedicine.org/centers-and-programs/usc-liver-health-center/
• Norah A. Terrault profile: https://www.keckmedicine.org/provider/norah-anne-terrault/
• Keck Medicine news boilerplate: https://news.keckmedicine.org/boilerplates
  References: Study published in Clinical Gastroenterology and Hepatology (DOI as above).
  Image Credits: Ricardo Carrasco III
  Keywords: Liver, Metabolic syndrome, Metabolic disorders