Testing for hepatitis C virus (HCV) 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 do not have chronic infection. 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
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
The systematic review was not able to assess the performance
of HCV antigen assays across different HCV genotypes or in people with HIV/HCV co-infection 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.