Six-question risk score can identify HIV-positive gay men needing testing for acute hepatitis C

Six questions can identify HIV-positive gay men who are at elevated risk of having acute (recent) hepatitis C infection and who would benefit from further testing, according to a paper published in Eurosurveillance last week. The risk score was based on data from a Dutch cohort and has been validated with separate datasets from Belgium, the Netherlands and England.

Better targeted testing of hepatitis C for gay men living with HIV could reduce the number of tests done, lowering costs and facilitating implementation in settings such as sexual health clinics. There is a lack of recommendations on how to target hepatitis C testing.

Guidelines from the European AIDS Treatment Network recommend six-monthly testing of liver function and annual testing for antibodies, for HIV-positive gay men “at risk for contracting acute hepatitis C infection” – but don’t specify how clinicians should identify individuals who might be at risk. 

Glossary

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).

specificity

When using a diagnostic test, the probability that a person without a medical condition will receive the correct test result (i.e. negative).

sensitivity

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). 

case-control study

An observational study in which a group of people with an infection or condition (called ‘cases’) are compared with a group of people without the infection or condition (called ‘controls’). The past events and behaviour of the two groups are compared. Case-control studies can help us understand the risk factors for having an infection or a condition. However, it is difficult both to accurately collect information about past events and to eliminate bias from case-control studies.

observational study

A study design in which patients receive routine clinical care and researchers record the outcome. Observational studies can provide useful information but are considered less reliable than experimental studies such as randomised controlled trials. Some examples of observational studies are cohort studies and case-control studies.

Guidelines from the American Association for the Study of Liver Disease and the Infectious Diseases Society of America recommend that all HIV-positive gay men who have unprotected sex should have annual hepatitis C screening.

The six questions in the risk score concern self-reported behaviours:

  • Condomless receptive anal intercourse in the past six months (score 1.1)
  • Sharing of sex toys in the past six months (score 1.2)
  • Fisting without gloves in the past six months (score 0.9)
  • Injecting drug use in the past 12 months (score 1.4)
  • Sharing of straws to snort drugs in the past 12 months (score 1.0)
  • An ulcerative sexually transmitted infection in the past 12 months (score 1.4)

A man scoring a total of 2.0 or more would be recommended to be tested for acute hepatitis C.

Of note, the risk score was developed with data from HIV-positive gay men. As the prevalence of hepatitis C is much lower in HIV-negative gay men, the risk score is unlikely to be valid for use with men who don’t have HIV.

The risk score was developed from analysis of the association of acute hepatitis C with self-reported behaviour in 213 participants in the Dutch MOSAIC study. This is an observational cohort, enrolling HIV-positive gay men with acute hepatitis C (cases) and HIV-positive gay men without a history of hepatitis (controls).

It was validated with data from three other studies:

  • A Belgian case-control study, with data on 142 men from 2010 to 2013.
  • An English case-control study, with data on 190 men from 2003 to 2005.
  • Clinic surveys in Dutch sexual health clinics, with data on 284 men from 2007 to 2009.

In the MOSAIC cohort, the risk score had a sensitivity of 78%, in other words correctly identifying 78% of participants who had acute hepatitis C. In the three validation studies, sensitivity was 73%, 93% and 100% respectively.

In terms of specificity (correctly scoring men who did not have acute hepatitis C), in the MOSAIC cohort this was 79%. In the three validation studies, specificity was 66%, 56% and 61% respectively.

In each cohort, the risk score suggested that between 42 and 59% of the cohort should have testing for acute hepatitis C.

The area under the curve (AUC) was between 0.74 and 0.92 in each cohort.

While 2.0 was identified as the optimal cut-off for the score, the researchers provide data on the sensitivity and specificity in each cohort if different cut-off scores were used. For example, in the MOSAIC cohort, if a lower total score of 1.1 was used (rather than 2.0), the sensitivity and specificity would be 89% and 46% respectively. This indicates that fewer cases of acute hepatitis C would be missed, at a cost of providing testing to many more men who did not have hepatitis C.

If a higher score was used as the cut-off, for example 3.2, the sensitivity and specificity would be 48% and 94% respectively. This indicates that only half of those with acute hepatitis C would be recommended for testing, but that very few men who didn’t have hepatitis C would need to get tested.

The researchers say that because the sensitivity of their risk score is not close to 100% it should not be relied on as the only way to identify men for hepatitis C testing, but used alongside existing practices (such as testing individuals who have abnormal liver function test results). They also say that while the specificity of the risk score is not ideal, incorrectly identifying a significant number of men as possibly having hepatitis C when they do not, these men may still benefit from behavioural interventions to reduce their risk of acquiring hepatitis C.

The risk score can successfully identify HIV-positive men who have sex with men at risk for acute hepatitis C infection, conclude the researchers. They urge its use, especially at sexual health clinics and other testing locations where men are not regularly tested for hepatitis C or where liver function is not routinely measured. 

References

Newsum AM et al. Development and validation of the HCV-MOSAIC risk score to assist testing for acute hepatitis C virus (HCV) infection in HIV-infected men who have sex with men (MSM). Eurosurveillance 22: 21, 25 May 2017. (Full text freely available).