HCV core-antigen testing is a reliable way of detecting acute HCV infections in HIV-positive gay men

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Hepatitis C virus (HCV) core-antigen testing is a highly reliable way of diagnosing acute HCV infections in people living with HIV, investigators from the United Kingdom report in the online edition of Clinical Infectious Diseases. Core-antigen testing was as accurate as HCV polymerase chain reaction (PCR) testing – the current gold standard for diagnosing acute infections. Potential advantages of core-antigen over PCR testing include savings in time, money and staff resources.

“We argue…that increased use of HCV core-antigen testing in preference to qRT-PCR has potentially substantial benefits to the laboratory, patient, and to public health,” comment the authors.

There is an epidemic of sexually transmitted HCV among gay men living with HIV in the UK, western Europe and North America.



Something the immune system can recognise as 'foreign' and attack.

polymerase chain reaction (PCR)

A method of amplifying fragments of genetic material so that they can be detected. Some viral load tests are based on this method.

acute infection

The very first few weeks of infection, until the body has created antibodies against the infection. During acute HIV infection, HIV is highly infectious because the virus is multiplying at a very rapid rate. The symptoms of acute HIV infection can include fever, rash, chills, headache, fatigue, nausea, diarrhoea, sore throat, night sweats, appetite loss, mouth ulcers, swollen lymph nodes, muscle and joint aches – all of them symptoms of an acute inflammation (immune reaction).

ribonucleic acid (RNA)

The chemical structure that carries genetic instructions for protein synthesis. Although DNA is the primary genetic material of cells, RNA is the genetic material for some viruses like HIV.



When using a diagnostic test, the probability that a person who does have a medical condition will receive the correct test result (i.e. positive). 

Guidelines in the UK, Europe and the United States recommend that gay men living with HIV should be screened for HCV at six-monthly intervals using liver function tests and at least annually using HCV antibody testing.

However, delayed HCV antibody seroconversion has been observed in people living with HIV, and a significant number of people who clear HCV (and who may therefore still be antibody-positive) are subsequently re-infected with the virus.

As a result, it is recommended that people with abnormal liver function and/or high-risk exposure should be screened for HCV using PCR testing.

This type of test is expensive, time-consuming and requires specialist equipment and skilled staff.

A less expensive and less time-consuming test for acute HCV infection may be core-antigen testing. Investigators in Brighton therefore designed a study comparing the use of PCR and core-antigen screening to diagnose new HCV infection in people living with HIV.

Over 2000 people had liver function assessments at intervals of four to six months as part of their routine HIV care. Individuals with ALT (alanine transaminase) elevations above the upper limit of normal were screened for HCV infection using core-antigen testing, RNA testing and antibody testing.

The study lasted 20 months and over this period 111 people (5%) had new ALT elevations. Almost all were white gay men. The majority (80%) were receiving antiretroviral therapy; HIV viral load was undetectable in 75% and 56% had a CD4 count above 500 cells/mm3.

Fifteen cases of acute HCV were identified using PCR testing, with HCV viral load ranging between 61,000 to 14,800,000 iu/ml.

Core-antigen testing correctly identified all 15 acute infections, a sensitivity of 100%.

There were no false-positives using core-antigen testing, but there were two intermediate cases. One patient was re-tested on the same day and found to be HCV un-infected using both assays. The second patient became HCV RNA positive five months later (viral load 694,000 iu/ml), when he was also HCV core-antigen and antibody positive. The investigators were unclear if their initial result was a false-intermediate or whether they had detected an extremely early infection.

Including the false-intermediate, core-antigen testing, when compared to RNA testing, had a specificity of 98%, a positive predictive value of 88% and a negative predictive value of 100%.

HCV antibody results were positive in 9 of the 15 cases, a sensitivity of 60%. People who were HCV antibody-negative at the time of their HCV diagnosis took a median of 112 days to develop antibodies to the infection.

The investigators calculated that during the course of the study, use of antigen vs PCR testing would have resulted in a financial saving of $8160 in kits alone, with a further $3116 saved in staff time.

Core-antigen results were available on the day of testing compared to up to a week for PCR test results.

“We believe that national guidelines should now begin to consider HCV core-antigen testing as an integral part of their HCV screening algorithm for acute HCV infection,” conclude the authors.


Cresswell FV et al. Hepatitis C core antigen testing: a reliable, quick and potentially cost-effective alternative to hepatitis C polymerase chain reaction in diagnosis acute hepatitis C virus infection. Clin Infect Dis, online edition, 2014.