Liver disease has been referred to as the silent killer due to the fact that it might take years and still remains silent. Cirrhosis or liver cancer is typically diagnosed when it is too late. The BMJ, however, published a breakthrough study in 2025 which has proposed an innovative new instrument, the CORE (Cirrhosis Outcome Risk Estimator) that will enable estimating the 10-year risk of having severe liver complications based solely on regular blood tests. This model was developed by scholars of Karolinska Institutet, the University of Helsinki, and various foreign partners and can potentially change the way physicians can identify liver disease at an initial stage when it is still not observed.
The silent epidemic of liver disease.
One of the health threats that are increasingly growing the world over is liver disease. Cirrhosis is currently the 11 th most common cause of death globally and liver cancer is considered the best four causes of cancer related deaths.
The perpetrators are mostly:
Metabolic dysfunction related steatotic liver disease (MASLD) previously called fatty liver disease that is being experienced by over a third of the global population.
Alcoholic liver disease which still contributes to the majority of cases of cirrhosis in the West.
These two conditions are very preventable, but millions of people remain undiagnosed up to later stages. Prevention is based on the principle that, early on, before lifestyle and medical factors predetermine it, one can recognize high risk people and intervene, thereby making a difference.
Why Early Detection Matters
Cirrhosis is a gradual disease where the normal liver tissue is substituted by scar tissue. The liver is still operative in its early or compensated phase but time is running out. Early risk detection can enable:
Change of lifestyle including alcohol intake and diet.
Special treatments, such as antifibrotic medications that are still in development in the treatment of advanced fatty liver disease.
Cancer and varice surveillance which enhances long term survival.
Regrettably, conventional screening is done with such instruments as FIB-4 and NAFLD fibrosis score based on which they were not created to work with the whole population. They are good in the specialty clinics and they cannot detect silent disease among the general population.
Implementing the CORE Risk Score.
CORE (Cirrhosis Outcome Risk Estimator) was created in order to address this issue. It is a straightforward, non invasive framework, which forecasts 10-year risk of significant liver risks cirrhosis, liver breakdown, liver cancer and liver associated death.
It employs only five factors which are measured on routine basis:
Age
Sex
Aspartate aminotransferase (AST)
Alanine aminotransferase (ALT)
The glutamyl transferase (GGT)
These markers are already included in the usual liver panels implying that in most of the clinical settings, CORE can be used immediately.
The model was constructed based on the analyses of 480,651 adult individuals in Sweden with up to 28 years of follow-up and validated on the UK Biobank and FINRISK cohorts almost half a million other people.
CORE performs better than traditional tools.
The CORE model was obviously superior when directly compared to the most popular FIB-4 score:
Prediction accuracy (AUC): CORE vs FIB-4 0.88 vs. 0.79.
Increased sensitivity and specificity: More positive identification of actual high risk patients and minimization of false positives.
Better calibration: Predictions compared well with the real life in all the investigated populations.
That is, CORE provides a more accurate and precise image of people who are truly at high risk of liver disease many years before clinical manifestation.
Available, Low price and Portable.
CORE is beautiful in that it is practical. The necessary data are all available due to the regular lab tests that the majority of people have at their annual check up.
In Karolinska University Hospital, the researchers estimated that CORE could cost less than half of FIB-4 to calculate (approximately less than half of $5.70 vs. $12 per patient).
In order to make it accessible worldwide, the team developed an interactive online calculator found on the site: www.coremodel.com.
and released open source software to allow hospitals to interface it with electronic medicals.
This has enabled it to be a very public health ready instrument, rather than a mere academic model.
What the Results Reveal
The researchers found 7,168 major liver outcomes in 12.3 million years of follow up. The risk of occurring a serious liver event was 0.27 over a 10-year period overall, whereas the risk increased with an increase in enzyme levels.
People in the 10 percentile CORE scores were found to be at a significantly greater risk of 15 times that of the 10 percentile CORE score.
Women and older adults demonstrated different risk patterns, although CORE was able to forecast the outcomes in both groups.
A CORE score ≥0.4% equated to the same caution zone as a FIB-4 of 1.3, while ≥5% indicated a high risk category requiring further testing.
The authors concluded that CORE helps to close the gap between the general population screening and specialist diagnostics.
Transforming Primary Care
The possible medical effect is colossal. CORE would have the potential of automatically identifying at risk patients during any blood test, as it is automatically integrated into electronic health records. Primary care physicians could in turn:
Early warn patients of possible liver risk.
Prescription of imaging, referral or counseling in high risk cases.
Detect risk mitigation after treatment or lifestyle change.
Such a proactive strategy is similar to the redesign of heart-disease prevention by cardiovascular risk calculators (such as QRISK) except that this time it is the liver being renamed.
Limitations and Next Steps
Even though CORE did a great job, the researchers concede that there were certain weaknesses:
It had been originally created based on Swedish health data of 1985-1996, but its strength was also demonstrated with the use of the UK and Finnish datasets.
It might also need additional calibration to non European groups or areas where viral hepatitis is common.
It still requires more studies to establish its efficacy in patients with diabetes, obesity, or increased alcohol consumption the most at risk groups in the modern world.
The next steps are real time clinical implementation, wearable health platform integration, and cost effectiveness modeling. Liver medicine has been dedicated to late stage therapy decades ago. CORE model is a change to proactive prevention. With the same method that transformed the field of cardiovascular care predictive scoring, now healthcare providers can be able to predict risk decades prior to the disease.
The implications of this study are not only limited to hepatology. It highlights the potential of machine learning and population data to make personalized medicine a reality, affordable, and fair.
According to the author of the article, the primary author, Dr. Jonas Soderling, the CORE can be applied to anyone who has undergone a normal liver panel. It implies that prevention does not have to wait until it is symptomatic, but it can start now.
Reference
Söderling J, Sigurdardottir R, Heliö T, Törngren T, Färkkilä M, Färkkilä N, Danielsson J, Hagström H. Use of new CORE risk score to predict 10-year risk of liver cirrhosis in general population: cohort study. BMJ. 2025;390:e083182. doi:10.1136/bmj-2024-083182.