Testing for hepatitis C virus core antigen could eventually replace the current two-step procedure for diagnosing chronic hepatitis C infection in lower- and middle-income countries, speeding up access to treatment and improving retention in care, a systematic review designed to inform World Health Organization hepatitis C testing guidelines has found.
Chronic hepatitis C infection is currently diagnosed by antibody testing followed by a confirmatory nucleic acid test to detect HCV RNA, which indicates active viral infection. The second step is essential because between 15 and 50% of people with HCV antibodies will have spontaneously cleared HCV infection during the first six months after exposure and are not chronically infected. Nucleic acid testing must be done by a laboratory equipped to carry out molecular testing. Nucleic acid testing is costly and inaccessible in many places. As a result an unknown proportion of people who test positive for HCV receive no confirmatory testing and are lost to follow-up, resulting in lack of monitoring and treatment.
The two-step diagnostic process is seen as a major obstacle to diagnosis and treatment of hepatitis C on the scale needed to achieve ambitious targets for reducing the burden of the disease and eliminating hepatitis C as a public health problem.
Hepatitis C core antigen can be detected soon after infection, before the development of antibodies to the virus, and remains detectable throughout chronic infection. Tests for core antigen do not require molecular testing equipment and currently available tests can be carried out in any laboratory that can do antibody testing. A rapid point-of-care test for HCV antigen that could be used by health care workers in the same way as point-of-care tests for HIV or HCV antibodies was viewed as the highest priority for improving HCV diagnosis, and a feasible target for product development, by a recent stakeholder consultation convened by the Forum for Collaborative HIV Research and the Foundation for Innovative Diagnostics (FIND).
HCV antigen testing also has the potential to reduce the cost of diagnostic testing, and of treatment monitoring if it is found to be comparable with HCV RNA testing for detecting sustaining virologic response to treatment. HCV RNA tests can cost between $13 and $100 per test, and the cost of diagnosis and monitoring may increase the overall cost of curing hepatitis C by one-third in some settings. In contrast currently available HCV antigen tests cost between $10 and $50 per test.
The review, published in Annals of Internal Medicine on 20 June, compared the sensitivity and specificity of five commercially available tests for hepatitis C core antigen compared to nucleic acid testing for HCV RNA. The review found 44 published studies comparing one of the selected assays.
The study found two assays – the Abbott ARCHITECT HCV Ag assay and the Ortho HCV Ag ELISA – almost matched nucleic acid testing in sensitivity and specificity where HCV viral load was above 3000 i.u./ml. Meta-analysis found that the Abbott ARCHITECT assay had a sensitivity of 93.4% and a specificity of 98.8%. The Ortho HCV Ag ELISA had a sensitivity of 93.2% and specificity of 99.2%. The authors conclude that higher-quality evidence was available for the Abbott ARCHITECT than the Ortho HCV Ag ELISA assay, owing in part to the larger number of published studies.
Less evidence was available regarding two other assays, the Eiken Lumispot and the Fujirebio Lumipulse, which use the same processes as Abbott ARCHITECT, and these studies reported on sensitivity only. The Hunan Jynda ELISA had the lowest sensitivity (59.5%) and the authors concluded that ELISA assays are probably a less reliable technology for HCV antigen detection than assays which use signal amplification that allows enhancement of antigen detection.
The systematic review was not able to assess the performance of HCV antigen assays across different HCV genotypes or in HIV/HCV co-infected people due to lack of data.
The review did not cover the use of HCV antigen assays in the monitoring of treatment responses and the authors say that more research is needed to define whether HCV antigen testing can replace HCV RNA testing.
The World Health Organization will issue new guidance on viral hepatitis testing at the 21st International AIDS Conference (AIDS 2016) in Durban, South Africa in July.