Hepatocellular carcinoma (HCC), a form of liver cancer, is the sixth most prevalent cancer globally and the third leading cause of cancer-related deaths. Current screening for HCC typically targets individuals with viral hepatitis or those with irreversible liver damage, such as cirrhosis. However, due to rising obesity rates, a new risk factor, metabolic dysfunction-associated steatotic liver disease (MASLD), has emerged but is not currently included in screening protocols. To address this gap, researchers have developed and validated a new risk score for HCC that incorporates MASLD along with other key factors.

A research team from Yale School of Medicine (New Haven, CT, USA) and the University of Pennsylvania (Philadelphia, PA, USA) conducted a cohort study utilizing data from over six million adults in the Veterans Health Administration (VA) electronic health records. They excluded individuals with known hepatitis B or C infections or decompensated cirrhosis. For their analysis, they selected one outpatient visit per patient from 2007 to 2020, collecting variables such as age, sex, race, body mass index, FIB-4 (a measure of liver fibrosis), and information about diabetes, smoking, and alcohol consumption. The study tracked these patients until they were diagnosed with HCC, died, or the study concluded. Out of the 6,508,288 individuals studied, 15,142 developed hepatocellular carcinoma. The findings, published in JAMA Network Open, highlight the development and validation of a new risk score for HCC.

While FIB-4 proved to be the most important variable for predicting the risk of liver cancer, other factors such as obesity and diabetes also showed a strong and independent correlation with the disease’s incidence. FIB-4, which has previously been validated for viral, alcoholic, and steatotic liver diseases, was broken down into its individual components—AST, ALT, platelets, and age—and continuous, rather than categorical, variables were used in the final model. This approach significantly enhanced the accuracy of the prediction model.

The goal of this new risk score is not to identify one single factor as the most significant, but to assess the combined effect of multiple factors that contribute to the risk of HCC in individuals, showcasing the potential of precision medicine. The researchers found that their risk score outperformed FIB-4 alone, offering higher sensitivity and positive predictive value, and it also revealed a gradient of risk among patients with specific FIB-4 scores. The team aims to validate this risk score in other healthcare settings beyond the VA, with the ultimate aim of improving primary care practices. The variables used in this study are easily measurable in routine primary care, and the researchers hope this will help patients better understand the modifiable risk factors for liver disease.

“Factors such as smoking and obesity not only contribute to the development of cardiovascular disease but also to liver disease,” said Amy Justice, MD, PhD, C.N.H. Long Professor of Medicine (general medicine) at Yale School of Medicine and one of the principal investigators of the study. “Recognition and modification of these risk factors is essential to improving health outcomes.” 

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