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.

Related Videos
Rates of obesity appear to correlate with increasing incidence of cancer in young populations, according to Monique Gary, DO, MSc, FACS.
Data from a ctDNA analysis of the phase 3 INTRIGUE study indicate that KIT mutational status may be associated with response to certain Tyrosine kinase inhibitors in GIST, according to an expert from the Yale Cancer Center in New Haven, Massachusetts.
Future research into the management of unresectable hepatocellular carcinoma may involve combining local therapies with checkpoint inhibitors like durvalumab and tremelimumab, according to Ghassan K. Abou-Alda, MD.
Patients with unresectable hepatocellular carcinoma who have recurrent disease following surgery or locally advanced diseases who will likely progress on local therapy may have an opportunity to benefit from tremelimumab and durvalumab following its FDA approval, according to Ghassan K. Abou-Alfa, MD.
Ghassan K. Abou-Alfa, MD, discusses the importance of improving access to novel therapies and combinations for patients with hepatocellular carcinoma across the world.
Ghassan K. Abou-Alfa, MD, spoke about the recent approval of tremelimumab plus durvalumab for patients with unresectable hepatocellular carcinoma, based on results from the phase 3 HIMALAYA trial.
Howard A. Burris, MD, highlighted previous findings of the phase 3 TOPAZ-1 trial assessing durvalumab plus gemcitabine and cisplatin vs placebo plus gemcitabine and cisplatin in advanced biliary tract cancer and patient-reported outcomes (PRO)data that were presented at 2022 ASCO.
Shubham Pant, MD discusses key findings from a basket trial examining the use of erdafitinib in patients with gastrointestinal cancers.
Related Content