Blood Test May Help Identify Individuals Likely to Develop HCC

Researchers have developed a new blood test that may help in identifying individuals who are likely to develop hepatocellular carcinoma.

Researchers have developed a new blood test that may help in identifying individuals who are likely to develop hepatocellular carcinoma (HCC), according to study results published in Cell.1

"Together with existing screening tests, the new test could play an important role in screening people who are at risk for developing HCC,” study leader Xin Wei Wang, PhD, co-leader of the NCI Center for Cancer Research (CCR), said in a press release.2 “It could help doctors find and treat HCC early. The method is relatively simple and inexpensive, and it only requires a small blood sample."

In this study, investigators profiled serological samples from 899 people currently enrolled in a National Cancer Institute-University of Maryland (NCI-UMD) case-control study of liver cancer, including 150 who had HCC. They then used a synthetic virome technology, titled VirScan, to detect the exposure history of these individuals to more than 1000 human viruses.

Using this high-throughput method, researchers developed a unique viral exposure signature (VES) that could discriminate HCC cases from at-risk or healthy volunteers. They then validated this signature in a prospective cohort of 173 individuals with chronic liver disease who were part of a 20-year study. During that time, 44 of the participants developed HCC.

Overall, the viral exposure signature was significantly associated with HCC status among at-risk individuals in the validation cohort (area under the curve: 0.91 [95% CI 0.87-0.96] at baseline and 0.98 [95% CI 0.97–1] at diagnosis). Moreover, the signature was able to identify patients with cancer before a clinical diagnosis and was found to be superior to alpha-fetoprotein.

“Remarkably, this signature was able to identify individuals at a median follow-up year of 8.8 prior to a clinical diagnosis of HCC,” the authors wrote. “Thus, our results may offer a sensitive tool applicable to the HCC surveillance pro- gram to improve early diagnosis.”

In addition, by comparing VirScan results as predicted values of HCV and HBV status against those from medical charts of the NCI-UMD cohort as true values, researchers found that VirScan demonstrated better accuracy (0.73; 95% CI, 0.67-0.79), sensitivity (0.84; 95% CI, 0.77-0.89), and positive predictive values (0.80; 95% CI, 0.76-0.84) for HCV than the accuracy (0.48; 95% CI, 0.41-0.54), sensitivity (0.48; 95% CI, 0.40-0.57), and positive predictive values (0.55; 95% CI, 0.49-0.61) for HBV.

Notably though, these data suggested that the current survey methods may have underestimated the prevalence of HBC and HCV, which are both major causative factors for HCC. Even further, due to a significant portion of missing data for medical tests results for HBV, researchers were not able to perform in-depth correlation analysis of HBV genotypes and VES-based viral loads.

“This is a limitation of this study,” the authors wrote. “It is worth speculating that cancer-prone individuals may perceive viral epitopes differently compared to healthy individuals. An in-depth correlative analysis between individual viral epitopes, a host’s TCR and BCR profile and genetic background may help to understand mechanisms of anti- tumor immunity.”

Moving forward, the researchers suggested that they are continuing to study this approach and plan to test it in clinical trials. Specifically, they are collaborating with Katherine McGlynn, PhD, of NCI's Division of Cancer Epidemiology and Genetics, to test the approach in a prospective surveillance study of people with risk factors for HCC.


1. Liu J, Tang W, Budhu A, et al. A Viral Exposure Signature Defines Early Onset of Hepatocellular Carcinoma. Cell. doi:10.1016/j.cell.2020.05.038.

2. NIH scientists develop blood test to help improve liver cancer screening [news release]. NIH/National Cancer Institute. Published June 11, 2020. Accessed June 29, 2020.