In 2003, the CDC published recommendations on the laboratory testing and reporting of hepatitis C virus (HCV) infection. The guidance focused on testing for the HCV antibody, a marker of HCV exposure. Since 2003, several efficacious antiviral drugs have been approved by the FDA for the treatment of hepatitis C. “These newer drugs are increasingly being prescribed by physicians,” says Chong-Gee Teo, MD, PhD. “They offer patients the likelihood of a cure from hepatitis C.”
Rapid testing for the HCV antibody with similar sensitivity and specificity to bench testing has also become widely available in the last decade. In addition, there has been increasing evidence that many patients who are reactive to an HCV antibody test are not then tested for current HCV infection. As a result of these developments, the CDC updated its guidance on HCV testing and published it in the Morbidity and Mortality Weekly Report.
“The current CDC guideline is geared toward identifying current infection with hepatitis C,” says Dr. Teo, who co-authored the document. “Rather than targeting the HCV antibody as a marker of infection, the target of testing is now the actual HCV genome itself, or HCV RNA. This is a marker of the virus in the blood and, therefore, current infection.” The concern with focusing testing only on the HCV antibody is that this approach cannot distinguish between patients whose past HCV infection has resolved and those who are currently infected. A reactive result to an HCV antibody test can also be a false-positive.
Accurate testing of current infection through HCV RNA testing helps identify patients who require preventive services, counseling, and treatment. Patients with current HCV infection should be distinguished from those whose infection has resolved because antiviral treatment is intended only for individuals with current infection. Accurate testing also enables patients to make informed decisions about their care as well as their options for HCV treatment. These decisions can be based on infection status and allow patients to take measures to limit disease progression and minimize the risk of transmitting HCV to others. Lastly, the CDC notes that it is important to inform patients who are not currently infectious of their HCV status.
A New Testing Sequence
Antibody testing still has a place in HCV infection testing. The CDC recommends that testing begin with either a rapid or laboratory-conducted assay for HCV antibodies (Figure). “If a patient is HCV antibody negative, there is often no need to test that person further,” explains Dr. Teo. “If they are antibody reactive, the next step is to test for HCV RNA. If the HCV is not detected, that patient does not require further testing in most circumstances. If the patient is HCV RNA-positive, a linkage to treatment and care should be made.”
With the new testing algorithm, there are four possible test outcomes (Table). A patient who is HCV antibody non-reactive can be considered not previously or currently infected by HCV. “If the patient tests antibody reactive and if an HCV RNA test is not performed, that person can be considered presumptively HCV infected,” Dr. Teo says. “That person should be tested for HCV RNA. If a patient is antibody reactive and HCV RNA is detected, that profile signifies current infection. Such a patient would need to be offered counseling and be linked to care and treatment. The last outcome is with the antibody being reactive but HCV RNA not being detected. This patient can be considered to have a resolved HCV infection or to have had a false-positive HCV antibody test, and for most cases, no further action is required.”
On The Horizon
According to Dr. Teo, an important advancement that is being developed to assist with HCV testing is the use of HCV antigen testing as a marker of current infection. “The HCV antigen marker tests for HCV protein in the blood,” he says. “These tests are being used in Europe and Japan, but the FDA has not approved these tests for use in the United States as of yet. That said, the manufacturers of HCV antigen tests may approach the FDA for product approval in the near future.” If and when that happens, Dr. Teo says the current CDC recommendations will be revisited and updated.
In the meantime, Dr. Teo urges physicians to test all baby boomers—those born from 1945 to 1965—to identify more hidden HCV infections among this highly affected population. When identified, these individuals can then be encouraged to get treatment with antiviral therapies. Dr. Teo says the latest CDC recommendations can be used to guide this testing and any subsequent care that may be necessary.
Readings & Resources (click to view)
Getchell J, Wroblewski K, DeMaria A, et al. Testing for HCV infection: an update of guidance for clinicians and laboratorians. MMWR Morb Mortal Wkly Rep. 2013;62:362-365. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6218a5.htm.
Poordad F, Dieterich D. Treating hepatitis C: current standard of care and emerging direct-acting antiviral agents. J Viral Hepat. 2012;19:449-464.
Shivkumar S, Peeling R, Jafari Y, et al. Accuracy of rapid and point-of-care screening tests for hepatitis C: a systematic review and meta-analysis. Ann Intern Med. 2012;157:558-566.
Morgan R, Baack B, Smith B, et al. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma. A meta-analysis of observational studies. Ann Intern Med. 2013;158:329-337.