Hepatitis C virus testing recommendations for men who have sex with men (MSM) are changing in response to the rising incidence of HCV in this group, among whom HIV and HCV coinfection is a leading cause of hospitalization and death. Lack of appropriate HCV testing is at least partially behind HCV’s spread among MSM—especially those with HIV—as MSM with undiagnosed disease become infected during risky sexual behavior and drug use.

Guidelines are now recommending more routine risk assessment and screening for HCV infection in MSM, particularly those with HIV infection. U.S. Centers for Disease Control and Prevention (CDC) recommendations issued in 2010 call for HCV antibody testing for newly diagnosed HIV-positive patients, HCV RNA testing in those with positive HCV antibody results, and annual screening for those at high risk of HCV. However, they don’t specify who is high risk.

Guidelines from the U.S. Department of Health and Human Services (HHS), updated in November 2014, also recommend HCV screening upon HIV diagnosis and annually thereafter if patients are at high risk for HCV. Risk factors include unprotected anal intercourse, use of sex toys, non-injection recreational drug use, and coinfection with other sexually transmitted diseases, HHS says. 2014 guidelines from the Infectious Diseases Society of America (IDSA), American Association for the Study of Liver Disease (AASLD), and the International Antiviral Society-USA are similar, but also recommend HCV screening in response to alanine aminotransferase (ALT) elevation detected during routine HIV treatment. British HIV Association and European AIDS Treatment Network guidelines also suggest screening HIV-positive MSM for HCV every 6 months with ALT and yearly with anti-HCV antibody.

ALT Elevation: Not Always a Screening Trigger

A recent study shows that ALT elevations found during HIV care usually do not trigger additional HCV screening, as IDSA-AASLD guidelines suggest. The analysis of data from 17,090 U.S. patients shows that 85% had HCV screening at presentation of care. However, the vast majority with ALT elevations >100 IU/L during subsequent care—73.3%—had no additional HCV testing (Clin Infect Dis 2014;59:1686–93). Screening rates varied widely among the study sites, highlighting the need for guidelines that define more definitively whom to screen, how frequently, and what screening tests are most appropriate, according to the authors.

“Acute HCV infection should be considered in patients with abnormal or new elevations in ALT,” said first author J. Morgan Freiman, MD, a fellow in infectious diseases at Boston Medical Center. If U.S. guidelines were to recommend more frequent HCV screening using ALT, those guidelines should define an ALT threshold that would trigger HCV testing, she added.

Missing Acute HCV Cases

Meanwhile, another study published alongside Freiman’s implies that many cases of acute HCV in HIV-positive MSM may go undetected, even in patients successfully treated for previous HCV infections. Researchers in the Netherlands showed that among HIV-positive MSM, HCV seroconversion takes 74 days on average, similar to the time to seroconversion among HIV-negative individuals. But among 27% of men studied, no HCV antibodies were detected 4 months after estimated date of infection. For this reason, acute HCV screening is best done with nucleic acid testing rather than antibody testing, according to the authors (Clin Infect Dis 2014;59:1678–85).

These findings support the IDSA-AASLD recommendations, said lead author Joost Vanhommerig, MSc, a doctoral candidate in molecular epidemiology at the Academic Medical Center of Amsterdam and the Public Health Service of Amsterdam. “Elevated ALT concentrations should trigger follow-up testing for HCV. Start with antibody, then do follow-up RNA or antigen testing, depending on ALT level or when risk behavior is disclosed. If you stick with 74 days as the average window for seroconversion, you could also repeat the antibody test in two to three months,” he explained.

Vanhommerig’s study also found that HCV antibodies following clearance of infection was fairly common, occurring in 37% of patients 3 years later. This result implies that antibody testing alone often misses diagnosis of early acute HCV, allowing more liver fibrosis and HCV transmission, and less effective response to some HIV antiviral therapies, notes an accompanying editorial by Thomas Reiberger of the Medical University of Vienna, Austria. Both Freiman’s and Vanhommerig’s studies show the need for broader use of sensitive quantitative polymerase chain reaction (PCR) RNA testing in HIV-positive MSM to prevent potential transmission of acute HCV and prompt earlier antiviral therapy, Reiberger suggested (Clin Infect Dis 2014;59:1694–5).

Screen More MSM?

Even as Freiman’s and Vanhommerig’s studies suggest the need for updated HCV testing practices in MSM with HIV, other British researchers recommend extending routine HCV screening to all MSM, regardless of HIV status, based on widespread risky activities among their MSM study population (J Int AIDS Soc 2014;174(4 Suppl 3):19591).

HCV screening regardless of HIV status would probably be more cost-effective in men who report high-risk behavior, said co-author Chris Ward of the Manchester Centre for Sexual Health.

A Lower Cost Screening Alternative

With cost-effectiveness in mind, researchers in Britain have urged consideration of quicker and cheaper HCV core antigen tests, which are available in Europe but not in the U.S. Antigen testing someday might enable more widespread and frequent screening, they wrote in a paper comparing this method with HCV PCR testing for diagnosing acute HCV infection (Clin Infect Dis 2015;60:263–6).

HCV core antigen testing with the Abbot Architect platform shows the test had 100% sensitivity and 97.96% specificity in patients with elevated ALT, the study found. Exclusive use of core antigen tests in place of PCR in the study cohort over the 20-month study period would have saved $8,160 in kit costs and about 14 days of manpower or about $3,118, the researchers estimated. They called for a larger study with further cost analyses.

Use of cheaper core antigen tests could enable clinics to test more patients and pick up more acute HCV, manage it, and counsel MSM to stop risky behaviors that contribute to spread of the disease, said senior author Mohammed Osman Hassan-Ibrahim, a consultant virologist and microbiology and laboratory lead in the Department of Microbiology and Infection at Royal Sussex County Hospital in Brighton. Core antigen tests as single assays are appropriate only for acute HCV, not chronic disease, he noted.

In Britain, use of HCV antigen tests to screen for HCV is growing, said Ward. Because they deliver high sensitivity and specificity with more speed and lower cost, these tests are a logical choice. But HCV antibody is still essential to determine HCV exposure, he emphasized.

“Now there’s antibody, antigen, ALT, and RNA testing possible. We have to make up our minds to see what’s the best testing algorithm and what’s (most) cost effective,” said Vanhommerig. He called for future guidelines with algorithms that better specify the situations in which specific HCV tests are best used. 

Deborah Levenson is a freelance writer in College Park, Maryland. +Email: dlwrites@verizon.net