Johns Hopkins hepatologist Amy Kim and a team of colleagues developed a new screening test for liver cancer that, when added to the current standard-of-care test, can detect liver cancer earlier than the existing test by itself.

As many physicians know, patients whose hepatocellular carcinoma (HCC) is found in its early stages have treatment options that can be curative. The five-year survival rate for patients with liver cancer after liver resection or transplant is greater than 70%. But for patients whose disease was already advanced when it was detected, that percentage falls to less than 10%.

For people at high risk of developing liver cancer, hepatologists recommend HCC screenings every six months, which include an ultrasound and a blood test. Kim says that many patients have difficulty complying with two rounds of these tests in a given year.

“On top of that,” she says, “about half the people who have liver cancer don’t show the biomarker the test is designed to find.”

The standard for liver cancer screening is to use a blood sample to test the patient’s alpha-fetoprotein, a protein expressed by the AFP gene, located on chromosome 4 in the human genome. But the effectiveness of AFP tests can be limited, with successful detection ranging between 40% and 90%.

“Half of people with liver cancer simply have low levels of AFP,” says Kim. “On the other hand, some patients with liver disease can have elevated AFP levels that can be falsely positive.”

The other element of testing for liver cancer involves an ultrasound exam, during which hepatologists try to spot liver tumors.

Kim and her colleagues sought to learn whether a group of eight genetic biomarkers in urine that are known to be associated with hepatocellular carcinoma ¾ the most common form of liver cancer ¾ could be identified in ways other than blood tests. They winnowed the biomarkers down to three and, in 2022, in the British Journal of Cancer, the research team published results from their study of more than 600 patients in five medical centers. The researchers wanted to know whether any of the liver cancer biomarkers could be found in a urine sample.

“We know that there are DNA fragments from tumors that circulate in the bloodstream,” Kim says. Dead cells and other material, including circulating tumor DNA, get moved from the blood to the bladder for elimination. “So we wanted to test the feasibility of detecting circulating tumor DNA in urine.”

Kim says the Johns Hopkins study was done in collaboration with the Baruch S. Blumberg Institute, one of the nation’s leading centers for translational research related to hepatitis B and liver cancer. She says that this study is unique in that the researchers didn’t just compare the biomarkers to a healthy population.

“We compared to people who are at high risk for liver disease, such as people with hepatitis B and cirrhosis.”

Using a two-stage logistic model, the combination of urine ctDNA and the AFP test increased detection sensitivity from 40% to 77% in early-stage liver cancer, and from 62% to 92% in the very early stage of disease.

Kim says she and her collaborators will continue working on the urine test in hopes that one day it can be a first-line, completely noninvasive screening test that can be used at home. 

“Our findings in the study suggest that the urine panel may complement serum AFP as a more reliable screening test,” Kim wrote in the journal article.