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Novel Blood Test to Assess Liver Cancer Risk in Patients with NAFLD

By Yujin Hoshida, M.D. Ph.D.

An estimated 30% of people in the U.S. have nonalcoholic fatty liver disease (NAFLD). Patients with NAFLD have a 17 times increased risk of developing liver cancer.

Identifying which patients are at risk of NAFLD-associated liver cancer is challenging and it is unclear which patients with NAFLD should undergo the demanding liver cancer screening by ultrasound every six months. For patients at high risk, this protocol can be lifesaving. However, for patients at low risk, undergoing biopsies and repeated ultrasound could introduce harms with potentially limited benefit.

Researchers in UT Southwestern’s Liver Tumor Translational Research Program have developed a blood test to identify whether a patient is lower- or higher-risk for NAFLD-associated liver cancer. Knowing the risk level could help clinicians tailor appropriately aggressive screening protocols, saving the healthcare system and patients time and resources.

About the Research

Our team analyzed blood samples from an international pool of 409 patients with NAFLD. We identified a set of 4 serum proteins aberrantly present in the patients who developed hepatocellular carcinoma (HCC), the most common form of liver cancer.

In our longitudinal study, participants were stratified into high- and low-risk groups based on serum protein levels and observed for up to 15 years. Nearly 38% of those identified as high risk developed HCC. Zero patients in the low-risk group were diagnosed with HCC.

Our results suggest that patients who have low-risk based on their gene expression might not require close monitoring or invasive testing.

Most of the proteins we identified as being predictive of developing HCC were inflammatory and immune molecules, which suggests that inflammation plays a role in HCC development. We also demonstrated that the levels of these molecules can change along with therapies known to decrease risk of liver cancer such as bariatric surgery, immunotherapy, and cholesterol medications, suggesting its utility as a companion biomarker for these therapies.

Ongoing and Future Research

We intend to continue assessing the blood test in larger international trials. Our hope is to develop blood tests to assess cancer risk associated with other liver diseases such as alcohol-associated liver disease and hepatitis B.


Disclosure: Y. H. serves as an advisory board member for Helio Genomics, Roche Diagnostics, and Espervita Therapeutics, and shareholder for Alentis Therapeutics and Espervita Therapeutics.