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NEW YORK (Reuters Health) – In high-risk patients with asymptomatic hepatitis B virus (HBV) infection, a liquid biopsy shows promise in detecting early-stage hepatocellular carcinoma (HCC), according to Chinese and U.S. researchers.

In a paper online March 11 in PNAS, Dr. Yuchen Jiao of Peking Union Medical College, in Beijing, and colleagues explain that the assay they developed (HCCscreen) works by detecting HCC via cell-free DNA (cfDNA) alterations and proteins from the surface antigen of HBV.

In a training cohort of subjects with liver nodules or elevated serum alpha-fetoprotein (AFP) levels, the assay “robustly separated” the 65 with HCC from the 70 without it.

HCCscreen had a sensitivity of 85% and a specificity of 93%. “Both cfDNA and protein markers showed significant contributions to the identification of HCC,” the researchers note.

The team went on to use the assay on 331 patients with normal liver ultrasonography and serum AFP levels. A total of 24 positive cases were identified. Follow-up at six to eight months confirmed that four had developed HCC. No cases of HCC were seen in the 307 patients with negative findings.

In this setting, the assay showed 100% sensitivity, 94% specificity, and 17% positive predictive value – which the authors say is significantly higher than the positive predictive value previously obtained with screening for alpha-fetoprotein levels alone. In addition, all four tumors were detected at an early stage when they were less than 3 cm.

“With further validation and optimization, the HCCscreen assay based on cfDNA mutation and protein markers has the potential to efficiently screen high-risk population to detect liver cancer when it is still curable,” Dr. Jiao told Reuters Health by email.

Dr. Daniel A. Haber, who heads the Cancer Center at Massachusetts General Hospital in Boston, told Reuters Health by email, “There has been extensive interest in early detection of cancer using blood-based molecular testing, and nowhere is this more relevant than in liver cancer, since that is a type of cancer that only occurs in high-risk patients with liver cirrhosis (caused by viral, alcoholic or fatty liver disease), and treatment is only curative if small tumors are caught early.”

Dr. Haber, who was not involved in the new work, added, “There have been a number of proposed blood tests for early liver cancer, some using detection of circulating tumor cells in the blood (e.g. our own work) and others using circulating free DNA with cancer-associated mutations or abnormal patterns of methylation (e.g. work from Johns Hopkins and others). Here the team is using some mutation-detection strategies, in addition to looking at the DNA integration site for the hepatitis B virus.”

“Overall the test performs well technically, and the key question is what is the predictive value: 4 out of 24 patients (17%) who were positive for the test did develop liver cancer 6-8 months after being tested,” he said. “Looking to the future, I think it will be a question of combining different types of blood based tests, together with patient risk stratification and MRI imaging, so as to deploy the most reliable strategy for early liver-cancer screening in people who are at high risk.”


PNAS 2019.

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