CORE Score: New Blood Test for Early Detection of Severe Liver Disease

Liver disease has emerged as a growing public health concern, ranking as the third most common cause of premature death in several countries. The challenge lies in the disease's silent progression conditions like liver cirrhosis and hepatocellular carcinoma often advance to critical stages before symptoms appear, severely limiting treatment options and worsening patient outcomes. New blood test-based CORE Score accurately predicts risk of Severe Liver Disease a decade in advance.

"Joe being very brave ahead of his blood test" by Kradlum is licensed under CC BY 2.0.

The need for better screening tools has become increasingly urgent as liver disease rates continue to rise globally. Primary care hasn't had the tools to detect the risk of severe liver disease in time, creating a critical gap in preventive healthcare.

Breakthrough Study Findings

Researchers at the Karolinska Institute in Sweden, led by Dr. Hannes Hagström and Dr. Rickard Strandberg, developed the CORE score using data from one of the largest cohorts ever assembled for liver disease research. The study, published in The BMJ, analyzed data from 480,651 individuals with no known history of liver disease, with validation performed in an additional 473,997 people from the UK and Finland.

The CORE model combines five easily accessible clinical parameters: age, sex, and blood levels of three liver enzymes routinely measured during standard health evaluations aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). These enzymes serve as biomarkers reflective of hepatocellular injury and cholestasis, making them ideal indicators of underlying liver pathology.

The study's results were remarkable. Over a median follow-up period of 28 years, researchers observed 7,168 major adverse liver outcomes (MALO), including compensated and decompensated cirrhosis, hepatocellular carcinoma, liver transplant, and liver-related mortality. The overall 10-year risk of these combined outcomes was calculated at 0.27% in the screened population.

Most significantly, the CORE score achieved 88% accuracy in correctly identifying individuals who would develop severe liver disease within 10 years, compared to 79% for the FIB-4 test. This 9% improvement in predictive accuracy represents a substantial advancement that could prevent countless cases of late-stage liver disease diagnosis.

Expert Commentary and Clinical Implications

"This is an important step towards being able to offer early screening for liver disease in primary care," explains Dr. Hannes Hagström, adjunct professor at Karolinska Institute's Department of Medicine. The significance extends beyond mere detection, drug treatment is now available for treating people at high risk of developing liver diseases such as cirrhosis or liver cancer.

For patients with conditions like non-alcoholic fatty liver disease (NAFLD), early detection is crucial since approximately 70% of patients with type 2 diabetes have NAFLD, with about 20% showing signs of advanced liver fibrosis. Current clinical practice guidelines already recommend screening for NAFLD and advanced liver fibrosis in patients with type 2 diabetes, making the CORE score a valuable addition to existing screening protocols.

Implementation Challenges and Healthcare System Integration

While the CORE score represents a significant scientific advancement, its successful implementation faces several practical challenges. The researchers acknowledge that a major obstacle for implementation of any risk score into primary care is accessibility. A simple online calculator may not be sufficient for widespread adoption.

Current referral patterns reveal the scope of the challenge. Studies show that most patients with NAFLD (88.5%) are referred for investigation of abnormal liver enzymes, but only 11.5% of referrals include an assessment of liver disease severity. This suggests that many healthcare providers lack the tools and confidence to perform comprehensive liver risk assessments.

The healthcare workforce data further illustrates these challenges. Distance to hepatologist and practice waiting times significantly affect referral probability, with gastroenterologists more likely to treat rather than refer patients with certain liver conditions. The CORE score could help standardize decision-making and ensure appropriate referrals.

Future Directions and Validation Plans

The research team has outlined clear next steps for the CORE score's continued development. Priority areas include testing the score in populations at higher risk for liver disease, particularly people with type 2 diabetes or fatty liver disease. This is especially important given that patients with type 2 diabetes are at increased risk of developing cirrhosis, liver failure, and hepatocellular carcinoma.

The integration challenge requires systematic solutions. The researchers suggest that direct integration into healthcare systems, allowing CORE to be automatically calculated from laboratory results, would be essential for widespread clinical adoption. This approach would eliminate the need for healthcare providers to perform manual calculations and could seamlessly incorporate risk assessment into routine patient care.

A web-based calculator is already available at www.core-model.com for researchers and clinicians who want to test the score further. However, the ultimate goal is seamless integration into electronic health record systems that would automatically generate risk scores whenever the necessary blood tests are ordered.

Clinical Significance and Patient Outcomes

The potential impact of the CORE score extends far beyond simple risk stratification. Early detection of liver disease risk could fundamentally change patient outcomes, particularly given that hepatocellular carcinoma recurrence and mortality rates remain relatively high, with overall mortality rates around 9-11% across different populations.

For patients identified as high-risk through CORE scoring, several intervention options become available. Treatment with antiviral therapy for both hepatitis B and C significantly decreases HCC risk in patients with or without cirrhosis. Additionally, emerging therapies for metabolic-associated liver diseases show promise for preventing disease progression when initiated early.

The score's validation across multiple countries - Sweden, Finland, and the UK, demonstrates its broad applicability across different healthcare systems and populations. This international validation is crucial for a screening tool intended for global implementation.

Conclusion

The CORE score represents a paradigm shift in liver disease screening, offering primary care providers a simple, accurate tool for identifying patients at risk of severe liver outcomes. With its superior performance compared to existing methods and basis in readily available clinical parameters, CORE could enable the early detection and intervention that has long been missing from liver disease care.

The successful implementation of this tool requires coordinated efforts between healthcare systems, technology providers, and clinical practitioners to ensure seamless integration into routine care. As liver disease continues to rise globally, tools like the CORE score may prove essential for preventing the progression from silent liver damage to life-threatening complications.

The research team's commitment to making the tool freely available through online calculators and open-source code demonstrates the collaborative spirit necessary to address global health challenges. With continued validation and systematic implementation, the CORE score could mark the beginning of a new era in preventive liver care.