July 8, 2021 — A simpler version of a test for the hepatitis C virus (HCV) may open testing to people in areas where medical care is limited.
“Although not yet developed, such a test could be a game changer and have a substantial impact on the feasibility and cost of HCV elimination, especially in low- and middle-income countries,” says Madeline Adee, MPH, of Massachusetts General Hospital in Boston.
Adee and her co-researchers have proposed that in less wealthy countries or in areas of the U.S. where medical laboratories are few and far between, using a simple and cheap — but less accurate — test for HCV infection could identify more people who are infected with HCV and should be treated.
Hepatitis C infects the liver and can go undetected for many years, as it does not always cause symptoms. But long-term HCV infections can lead to scarring of the liver (cirrhosis), liver cancer, liver failure, and other serious medical problems.
The CDC recommends that all adults get tested at least once for hepatitis C infection. Testing is especially important for people who had a blood transfusion before July of 1992 (when testing of blood for hepatitis infections began), or received blood from a donor who later tested positive for HCV, the federal agency says. Testing is also recommended for people with liver problems, and health care workers, first responders, or others who may have been exposed to HCV-infected needles.
HCV can be detected with a blood test to check for antibodies to the virus. Yet more than 1 in 5 people who test positive with this method may have a false-positive result, meaning that there is no virus in their bodies.
A more accurate test for HCV measures the level of hepatitis virus genetic material (HCV RNA) in a patient’s blood. This test is nearly 100% accurate, but it must be analyzed in a high-quality clinical laboratory.
Once HCV is diagnosed, people who are infected can be closely followed by their doctors, and those who need it can be treated and usually cured with antiviral drugs over an 8- to 12-week course.
Since some under-developed nations, as well as geographically isolated areas of the U.S., have few, if any, medical laboratories available, the research team came up with a simple solution: They proposed using a simple and inexpensive blood test that looks for antibodies to the HCV core, rather than the virus’ genetic material.
Hepatitis C has a central core and surrounding envelope. In people who are infected with HCV, the immune system creates antibodies to the core. These antibodies are often not strong enough to fight off infection, but their presence in the blood is a strong sign of possible infection.
Under the current standard of care, people who have a positive result on an antibody-based rapid diagnostic test (RDT) for HCV infection have confirmation of the results with lab-based RNA testing.
Instead, Adee and co-researchers proposed, people who have an antibody test showing a possible infection could be retested with a core-antigen-based rapid test. People with uncertain core-antigen test results could then have lab-based RNA testing to confirm or rule out infection. Patients who test positive on the core-antigen test could start treatment without the need for further, expensive RNA testing.
To see whether this approach could work, the researchers created a theoretical mathematical model and applied it to two nations with high rates of HCV infection: the Republic of Georgia, where 5.4% of the population is estimated to have HCV infections, and Malaysia, where an estimated 1.5% of the population is infected. (For context: About 1% of the adult U.S. population is living with HCV infection, according to the CDC.)
Applying their proposed method to the Republic of Georgia would result in a 95.4% diagnosis rate, compared to 78.8% for lab-based RNA testing.
For Malaysia, the proposed method would boost diagnosis rates from 57.0% to 91.2%.
Cost savings, mostly from avoiding the costs of care for patients with HCV over 50 years, in Georgia would be $232,000 per 10,000 people, and the corresponding savings in Malaysia would be $504,000 per 10,000 people, Adee and colleagues calculated.
Their findings were presented at the International Liver Conference sponsored by the European Association for the Study of the Liver.
The proposed testing method would be likely to improve diagnosis, but whether that would translate into increased treatment is uncertain, says Lesley Miller, MD, who specializes in HCV screening and treatment in underserved populations at Emory University in Atlanta.
“When we’re talking about hepatitis C, it’s all about the care cascade, the drop-off at each step from those who have the disease and aren’t diagnosed, to those who are tested and only partially diagnosed because they don’t have a confirmed infection, to those that get into care, get treated, and get cured,” says Miller, who was not involved in the study.
“It’s all about closing the gaps in the care cascade in order to achieve elimination of the virus, which is what we’re all trying to do,” she says.
In the U.S., there are certain at-risk populations who might benefit from such a system, says Miller, using people who use injectable drugs as an example.
“These folks often have less access to traditional care, so bringing rapid testing and care to where those folks are is really important. So if we can deploy mobile units to areas where there is high prevalence and do it at the point of care, it simplifies the entire process,” she says.
Thomas J. Hoerger, PhD, a senior fellow in health economics and financing at the nonprofit research group RTI International in Research Triangle Park, NC, says the model proposed by Adee and colleagues could cut out the step in testing in which patients would be required to return to confirm their diagnosis.
“People don’t always come back for further testing, so if you can do it immediately and have the results of a screening test, you might be able to get people to come back more quickly. You still have the problem of the high cost of treatment, but this would at least make it a little more convenient,” he says.
Hoerger, who was not involved in the study, notes that the success of the strategy would depend on how sensitive the rapid core antigen test is, it’s cost relative to HCV RNA testing, and whether making the rapid test more available would translate into an improvement in follow-up.