Is HCV Birth Cohort Testing Broad Enough?

Hepatitis C virus (HCV) infection is highly prevalent in patients seeking care in urban emergency rooms, according to two separate studies that each demonstrate a prevalence of approximately 14 percent. In both studies published in the May issue of Clinical Infectious Diseases, roughly onethird of positive cases were previously undiagnosed and more than a quarter of these HCV-positive cases would have remained undiagnosed using current screening strategies, causing the authors to call for expanding birth cohort-based screening criteria.

Current screening strategies for HCV detection rely on the U.S. Centers for Disease Control and Prevention (CDC) birth cohort screening recommendations— one-time HCV testing in those born from 1945 to 1965—in combination with targeted risk-based testing. Given that emergency departments serve as a safety net for underserved patients that may be at high risk for HCV because of HIV status and/or intravenous drug use (IDU), and that emergency departments have shown some success as an HIV screening venue, they may be a strategic partner for expanding national HCV screening.

“While we cannot know with certainty the extent to which our findings are generalizable to other emergency departments, we suggest that undiagnosed HCV is likely to be endemic in the emergency department populations of all but the smallest and most rural centers,” writes lead author Michael Lyons, M.D., from University of Cincinnati (Ohio) in one of the studies. “As is the case with HIV, emergency departments are likely to provide a uniquely high level of access to populations with undiagnosed HCV who are in need of treatment.”

In the Cincinnati study, the researchers used samples from a repository of 924 emergency department patients, who consented and provided and self-reported information (2008 to 2009) as participants for an HIV prevalence study. Testing relied upon an enzyme-linked immunosorbent antibody assay and viral RNA testing (Qiagen), followed by real-time reverse transcription polymerase chain reaction (Bio-Rad).

The researchers detected HCV antibody in 128 of 924 (14 percent) of samples, with 44 of these (34 percent) from patients self-reporting a history of HCV or hepatitis of unknown type. In total, 103 of the 128 antibody-positive samples (81 percent) were RNA positive. Fully implementing birth cohort screening for HCV antibody would have missed 36 of 128 (28 percent) of cases with detectable antibody and 26 of 105 (25 percent) of those with replicative HCV infection.

Similarly, the second study, from Johns Hopkins Hospital Emergency Department (Baltimore, Md.), found that 25 percent of undocumented HCV infections would be missed using CDC guidelines.

The Johns Hopkins researchers conducted an eight-week seroprevalence study (2013) in patients with excess blood collected for clinical purposes. Demographic and clinical information, including documented HCV infection, was determined from electronic medical records. Testing used an HCV enzyme immunoassay (GreenCross Life Science) and HCV RNA was quantified (Abbott Laboratories) on 100 randomly selected samples of HCV antibody-positive samples.

The study showed that of 4,713 eligible patients, 652 (13.8 percent) were HCV antibody positive. Of these, 204 (31.3 percent) had undocumented HCV infection (4.3 percent of all tested). Among the 204 patients with undocumented HCV infection, 63 percent were in the 1945-1965 birth cohort, 22 percent were IDU, and 5 percent had known HIV infection, meaning that of patients with undocumented infections, 48.5 percent would have been diagnosed based on birth cohort testing, 26.5 percent would be identified by risk-based testing, and 25.0 percent would have been missed.

“Given an estimated 7,727 unique HCV antibody-positive patients attending the emergency department in a one-year period … there would be approximately 2,419 patients with undocumented infection,” write the authors led by Yu-Hsiang Hsieh, Ph.D., from Johns Hopkins. “However, 605 patients (526 with chronic infection) would be missed in an emergency department-based HCV testing program using current CDC testing recommendations.”

Takeaway: Given the high prevalence of HCV infection seen in urban emergency departments, expanding the target population of one-time HCV age-based screening may be appropriate.