23 Jun 2026
Liver disease often progresses quietly. By the time symptoms appear, significant damage may already have occurred, making early detection critical.
Two new studies published in Nature Communications and Diabetes, Obesity and Metabolism, co-authored by Margery Connelly, Ph.D., MBA, FAHA, strategic director, diagnostics research and development at Labcorp, highlight how blood-based tools may help clinicians better identify patients at risk of serious liver disease earlier in the care journey.
Why identifying at-risk MASH is so challenging
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease in the United States, affecting an estimated 38% of adults. While many individuals with MASLD may never develop complications, some progress to metabolic dysfunction–associated steatohepatitis (MASH), a more severe form that can lead to fibrosis, cirrhosis, liver cancer or death.
Current diagnostic approaches often involve multiple steps, including routine labs, FIB-4 scoring, imaging and sometimes liver biopsy, and may not always be practical in primary care or endocrinology settings. FIB-4 scoring, which estimates risk using common lab values, is helpful as a rule-out tool but does not directly measure liver inflammation or fibrosis and can overestimate risk in outpatient settings.
When results are inconclusive, the next step may involve imaging such as FibroScan. However, access to these tools is not always readily available in primary care or endocrinology clinics. As a result, some patients who need further evaluation may not be identified early enough.
Predicting Risk of Serious Outcomes in MASLD
In a study published in Nature Communications, researchers evaluated Labcorp’s Metabolic Vulnerability Index (MVX), a blood-based score derived from inflammatory and metabolic biomarkers, to assess its ability to predict disease progression and outcomes.
The study found higher MVX scores were strongly associated with worse outcomes over time. Specifically, every 10-point increase in MVX was linked to:
- 2.7x higher risk of all-cause mortality
- 5.1x higher risk of liver-related mortality
- 2.5x higher risk of liver decompensation
When combined with fibrosis stage, MVX improved prediction of all-cause mortality, liver-related mortality, liver decompensation and hepatocellular carcinoma (a common form of liver cancer) compared with fibrosis stage alone.
Supporting Earlier Identification of At‑Risk MASH
A second study, published in Diabetes, Obesity and Metabolism, focused on real-world clinical settings such as primary care and endocrinology.
Researchers evaluated 798 adults using the NIS2+ blood test, which measures biomarkers associated with liver inflammation and fibrosis.
The study revealed a substantial and often hidden burden of high-risk liver disease:
- 16% of the overall population had at-risk MASH
- 24% of patients with Type 2 diabetes had at-risk MASH
- 29% of patients with both obesity and Type 2 diabetes met high-risk criteria
These findings highlight how many patients in routine outpatient care may have clinically significant liver disease that has not yet been identified.
Because current diagnostic pathways can require specialized imaging that is not always accessible, the study suggests NIS2+ may offer a more practical way to screen and prioritize patients for further evaluation in everyday clinical workflows.
Why these findings matter for patient care
Taken together, these studies highlight two complementary opportunities for improving liver disease management:
- Earlier identification of patients with at-risk MASH in routine care using NIS2+
- Better prediction of long-term outcomes and disease progression with MVX
Both approaches use blood-based biomarkers, offering a less invasive and potentially more accessible alternative to traditional tools.
This may help clinicians:
- Identify high-risk patients sooner
- Stratify risk more accurately
- Prioritize follow-up and intervention
- Integrate liver disease assessment more seamlessly into existing workflows
Advancing a more proactive approach to liver health
As liver disease continues to rise alongside diabetes and obesity, the need for scalable, accessible and biologically informed risk assessment tools is growing.
While these studies do not suggest replacing current diagnostic methods, they demonstrate how blood-based testing can enhance existing approaches, helping close gaps in detection and enabling more proactive care.
By supporting earlier identification and better risk prediction, these tools may ultimately help clinicians intervene sooner and improve outcomes for patients who might otherwise remain undiagnosed until later stages of disease.
About the Author
Margery Connelly, Ph.D., MBA, FAHA, serves as strategic director for diagnostics research and development at Labcorp. Dr. Connelly is a scientific leader with expertise in cardiovascular, metabolic, liver and chronic inflammatory diseases. She received her Ph.D. in Immunology and Pathology from Stony Brook University and her MBA in Pharmaceutical and Healthcare Management from Drexel University.
In addition to Labcorp, Virginia Commonwealth University, the University of Florida, the University of Alabama and GENFIT contributed to these studies.