HCV core antigen tests a less costly diagnostic option

Several hepatitis C virus core antigen (HCVcAg) tests have high sensitivity and specificity and although not equal to nucleic acid testing, may cost less and improve diagnostic capacity in settings of high hepatitis C virus (HCV) prevalence, according to a new study.

The diagnosis of chronic HCV infection requires both a positive HCV antibody screen and confirmatory nucleic acid test (NAT). “We sought to review HCV core antigen tests as an alternative, less expensive confirmatory test,” J. Morgan Freiman, MD, infectious disease clinical research physician at Boston Medical Center, told Medical Economics.

Freiman and colleagues evaluated the accuracy of diagnosis of active HCV infection among adults and children for five commercially available tests compared with NAT in a systematic review and meta-analysis of 44 studies.

The researchers published their results in the June 21, 2016 Annals of Internal Medicine.

They found that “well-performing HCVcAg tests with an analytic sensitivity reaching into the femtomolar range (equal to 3000 IU/mL) could replace NAT for HCV detection, particularly if a lower cost per test allows more patients to be served.”

The pooled sensitivity and specificity were 93.4% and 98.8% for the Abbott ARCHITECT assay, 93.2% and 99.2% for the Ortho HCV Ag ELISA, and 59.5% and 82.9% for the Hunan Jynda HCV Ag ELISA. There was insufficient information for a pooled analysis of the Eiken Lumispot HCV Ag and the Fujirebio Lumipulse Ortho HCV Ag assays.

The highest performing HCVcAg tests require signal amplification, which will be a barrier in conversion to a point-of-care platform, noted Freiman. 

“There was not enough data of core antigen performed on HCV Ab negative specimens to examine core antigen tests as a stand-alone test to screen for and diagnose HCV,” she said. “Currently, HCVcAg platforms are less expensive than NAT, but more data is necessary to assess performance as a single-step test. Additionally, this study shows that the core antigen is a great potential target for a point-of-care tool.”

In the discussion section, the researchers note that the cost estimates are highly variable and often  country specific, though generally cost estimates for HCVcAg tests are lower (from $10 to $50) than for HCV RNA tests ($13 to $100).

“The question about clinical limit of detection necessary to achieve adequate sensitivity and specificity in a low-resource, high-prevalence setting remains to be answered, but that is the critical information needed for development of such a test,” said Freiman. “The study calls attention to the difficulty in diagnosis of HCV, particularly in low- and middle-income countries where NAT is not only expensive but the requirements of trained staff, clean water and reliable electricity are not always available.”

HCV elimination is a priority for the World Health Organization and “cannot be achieved without a massive increase in HCV screening and diagnosis. The current two-step diagnostic algorithm impedes the process not only because of loss to follow up between tests, but also because the costs and infrastructure necessary for confirmatory testing are not readily available and reliable in low and middle income countries,” said Freiman.