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Choosing the Right HCV Assay: How Does Patient Population Affect the Choice?
With a wide variety of HCV tests available, many clinicians are not sure what sequence of tests is optimal. A recent study re-evaluated the cost effectiveness of various HCV testing strategies, and the findings offer some new recommendations based on the prevalence in the tested group. This month Strategies looks at these various testing strategies, and what lab directors need to know when choosing from the menu of HCV assays.
Many clinicians believe that HCV testing should have a multi-pronged approach: antibody testing to determine exposure, and then additional assays to determine viral status. “If patients don’t have an active disease or virus, then there’s no real reason for treatment,” explained Michael Chapko, PhD, a health services researcher with the U.S. Department of Veterans Affairs (VA) Puget Sound Health Care System (Seattle, Wash.) and Associate Director of the VA Northwest Hepatitis C Resource Center. Because the standard HCV treatment of pegylated-interferon plus ribavirin typically lasts between 24–48 weeks, with side effects such as depression and fatigue being common, treatment is only indicated in the presence of detectable virus.
Although patients without ongoing, chronic HCV infection don’t require treatment, using the antibody test to determine if the patient has been exposed to HCV in the past is important, particularly if the physician suspects that the patient continued to engage in high-risk behavior such as intravenous (IV) drug use. “It’s important to find out if they’ve been exposed in the past, what they are doing now in terms of high-risk behaviors, and counsel them against doing anything that might get them into trouble in the future,” said Chapko.
Rates of hepatitis C infection in populations vary depending on the prevalence of risk factors such as receiving blood or blood products before the supply was screened or using illicit IV drugs. Among patients cared for in the VA health care system, the rate of HCV infection is 5%, considerably higher than the estimated 2% of the overall US population. The VA’s HCV testing and prevention guidelines call for not only an enzyme immunoassay (EIA) and recombinant immunoblot assay (RIBA) to identify HCV antibodies, but also analysis of the patient’s RNA by reverse transcription polymerase chain reaction (PCR) to determine if there is an ongoing infection. Guidance from VA’s Hepatitis C Program Office details three alternate algorithms, any of which is considered to be a reasonable testing approach.
- Algorithm #1: EIA-OD>RIBA (followed by PCR if specifically ordered by clinician). EIA is performed first and samples are classified as either antibody positive or negative, using optical density (OD) categorization. Samples that are designated low antibody-positive then proceed to RIBA, and then the results are designated as antibody-positive, indeterminate, or negative. The clinician can then order PCR to determine viral status, or viremia.
- Algorithm #2: EIA-OD>RIBA>PCR. This algorithm is the same as #1, with the exception that all samples designated antibody-positive or indeterminate on the basis of EIA-OD and RIBA are tested using PCR for viremia.
- Algorithm #3: EIA>PCR>RIBA. If the EIA signal-to-cutoff ratio is greater than or equal to 1, PCR is performed. If PCR is positive, then no further antibody testing is necessary, but if viral RNA is not detected, then a RIBA will be performed to determine antibody status.
Chapko and his colleagues at the VA Puget Sound Health Care System’s Northwest Hepatitis C Resource Center in Seattle took a closer look at these three algorithms, along with other testing strategies, to assess cost as well as sensitivity and specificity with regard to antibody and viral status. Their findings were published recently in the American Journal of Gastroenterology (2005; 100: 607–615).
While minor cost differences between testing strategies might be unimportant to lab directors performing only a small number of these tests, they become significant in large facilities, such as VA systems, where thousands of tests are done every year. For example, in 2001, the VA performed 480,000 antibody tests nationally. When comparing cost and performance factors, there is no dominant test, said Chapko. EIA is inexpensive, and has relatively good sensitivity and specificity. RIBA is considerably more expensive, but has better specificity compared to EIA, although little data exists on its sensitivity.
According to their decision analysis, Chapko and his colleagues found that the EIA-OD>RIBA>PCR is the best choice when the prevalence in the tested group is below 20%. When the prevalence is greater than 20%, they recommend the EIA>PCR. “It’s a bit of a tradeoff between those two as to which one you should choose and under what circumstances,” said Chapko. EIA>PCR identifies more people who are really positive with regard to antibody status, but it tends to generate a few more false positives than the more complex second strategy—the EIA-OD>RIBA>PCR.
Lab directors should consider the estimated prevalence of the population they are serving when deciding on a testing strategy. For example, if a lab director is testing someone in a public health or other clinic where the policy is to test almost everyone regardless of any other known information about the patient, then the EIA-OD>RIBA>PCR is probably the best strategy.
“On the other hand, if you are doing the testing in a clinical situation serving a high-risk group such as IV drug users, or if you know that the patient has several clinical symptoms that suggest that the patient might have HCV, such as a liver that isn’t functioning properly, then you might want to use EIA>PCR,” explained Chapko.
For more information:
The VA National Hepatitis C Program’s Diagnostic Testing Guidelines:
Hepatitis C Testing and Prevention Counseling Guidelines for VA Health Care Practitioners: