Blood test developed to predict liver cancer risk

An estimated quarter of adults in the United States have non-alcoholic fatty liver disease (NAFLD), excess fat in liver cells that can cause chronic inflammation and liver damage, increasing the risk of liver cancer. Now, UT Southwestern researchers have developed a simple blood test to predict which NAFLD patients are most likely to develop liver cancer.

“This test allows us to noninvasively identify who needs to be followed more closely with regular ultrasounds to screen for liver cancer,” said Yujin Hoshida, MD Ph.D., associate professor of internal medicine at the Division of Digestive and Liver Diseases from UTSW, a member of the Harold C. Simmons Comprehensive Cancer Center and senior author of the article published in Science Translational Medicine.

NAFLD is rapidly becoming a leading cause of chronic liver disease in the United States. With rising rates of obesity and diabetes, its incidence is expected to continue to rise. Studies have shown that people with NAFLD have up to seventeen times the risk of liver cancer. For NAFLD patients considered most at risk for cancer, doctors recommend a demanding screening program involving liver ultrasound every six months. But identifying patients who belong to this group is difficult and usually involves invasive biopsies.

Naoto Fujiwara, MD, Ph.D., a research scientist at the Hoshida Laboratory, and his colleagues wondered if blood samples from NAFLD patients could reveal those most at risk for hepatocellular carcinoma (HCC), the most common form of liver cancer. In the new study, they analyzed samples from 409 NAFLD patients to reveal a set of 133 genes expressed at above or below average levels in the livers of patients who developed HCC over a 15-year follow-up period. Patients were then stratified into high and low risk groups based on the amount of expression of these genes. More than 15 years after the samples were collected, 22.7% of people in the high-risk group were diagnosed with HCC while no patients in the low-risk group were diagnosed.

“This test was particularly good at telling us who was in this low-risk group,” said Dr. Hoshida, who directs UTSW’s Translational Liver Tumor Research Program. “We can now say with much more confidence that these patients do not need very close follow-up.”

The researchers also converted the liver gene panel into four proteins whose levels could be measured in blood samples to help with risk assessment. When patients were stratified into high- and low-risk groups based on these proteins, 37.6% of patients in the high-risk group were diagnosed with HCC during the 15-year follow-up period, whereas ‘no patients in the low-risk group were diagnosed. diagnostic.

Most of the genes and proteins found to be predictive of HCC risk were immune and inflammatory molecules, highlighting the importance of inflammation in the development of HCC. Additionally, the researchers showed that levels of the molecules changed in conjunction with therapies known to decrease liver inflammation and risk of HCC, including bariatric surgery, cholesterol medications and immunotherapy.

“This means that we could actually use these molecule panels to track the status of patients over time or to inform the potential effectiveness of medical interventions aimed at reducing the risk of liver cancer,” said Dr. Hoshida. . For example, the protein blood test, dubbed PLSec-NAFLD, is already being used to monitor the effectiveness of a cholesterol drug in reducing the risk of liver cancer in an ongoing clinical trial.

Dr. Hoshida’s team plans to continue evaluating the utility of PLSec-NAFLD in larger groups of patients around the world. They also say that in the future, blood tests may be developed to measure cancer risk in other major liver diseases such as hepatitis B and alcoholic liver disease.

Other UTSW researchers who contributed to this study include Naoto Kubota, Bhuvaneswari Koneru, Cesia Marquez, Arun Jajoriya, Gayatri Panda, Tongqi Qian, Shijia Zhu, Xiaochen Wang, Shuang Liang, Zhenyu Zhong, Amit Singal, Jorge Marrero , Indu Raman and Quan. -Zhen Li.

The study was funded by the National Institutes of Health (R01DK099558, R01CA233794, U01CA226052, U01CA230694 and R01CA222900), the Cancer Prevention and Research Institute of Texas (RR180016, RR180014 and RP200197), the American Association for the Study of Liver Diseases ( AASLDF 50028), a Uehara Memorial Foundation postdoctoral prize, AMED (JP21fk0210090 and JP21fk0210059), KAKENHI (21H02892), European Commission (ERC-2014-AdG-671231 and ERC-2020-ADG-101021417), and Inserm Plan Cancer and TheraHCC 20 .

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