Nontargeted Hepatitis C Screening Proves Superior in EDs

The DETECT Hep C trial randomly assigned 147,498 adult patient visits across 3 urban emergency departments in Denver, Colorado; Baltimore, Maryland; and Jackson, Mississippi, to either nontargeted or targeted hepatitis C virus (HCV) screening as part of routine care. In the nontargeted group (n = 73,847), HCV testing was universally offered, resulting in 9867 individuals (13.4%) being tested and 154 new diagnoses. In the targeted group (n = 73,651), 23,400 patients (31.8%) were identified as at risk based on factors such as birth cohort or injection drug use, with 4640 (6.3%) ultimately tested and 115 new HCV cases identified—a 34% relative increase in new diagnoses for the nontargeted approach (relative risk, 1.34; 95% CI, 1.05-1.70; P = .02).¹

“This was a labor of love,” said Jason Haukoos, MD, MSc, FACEP, an emergency physician and principal investigator of the trial. “This project has been in development and execution for about a decade now.”

Haukoos developed the trial with Sarah Rowan, MD, an infectious disease physician at Denver Health. “We came together about 10 years ago to develop this project, recognizing that hepatitis C is a smoldering, indolent infection that exists broadly in our populations. But it's often undiagnosed and silent until very late, when a proportion of patients develop liver disease and occasionally cancer.”

The team built the study on prior work in HIV screening. “It was the next logical step to transition that work to hepatitis C,” said Haukoos. “From an epidemiology perspective, hepatitis C affects about 10 times as many people as HIV, many of them undiagnosed. So we believed that this study—the trial—had the potential to be important in terms of identifying the best way to detect hepatitis C in the emergency department.”

When DETECT Hep C was first conceptualized, national guidelines still favored targeted screening—an approach that prioritized testing individuals based on birth year (1945-1965), known injection drug use, or other risk factors. “At that time, we felt it was really important to evaluate both strategies,” Haukoos said.

By the time the trial concluded, major organizations including the Centers for Disease Control and Prevention and the US Preventive Services Task Force had shifted to recommending universal, onetime screening for all adults. “The nontargeted approach had already been established in the HIV world—we’d done work in that space as well,” Haukoos added. “Given that hepatitis C was even more prevalent than HIV, we felt that nontargeted screening would likely be superior to targeted screening. That was our primary hypothesis.”

The findings affirmed that hypothesis. “Nontargeted screening was, in fact, superior to targeted screening,” Haukoos said. “It identified more patients and resulted in more individuals being tested, as you’d probably expect. More patients, even those who tested negative, ended up knowing their serostatus, which is a meaningful outcome in itself.”

Despite improved detection, follow-up care remained a challenge. Among patients newly diagnosed with HCV, only 19.5% in the nontargeted group and 24.3% in the targeted group engaged in follow-up care. Direct-acting antiviral treatment was initiated in 15.6% and 17.4% respectively, completed in 12.3% and 12.2%, and resulted in sustained virologic response at 12 weeks in just 9.1% vs 9.6% of cases.

Still, Haukoos sees the results as an important step forward. “It was a positive trial. It definitively showed that nontargeted screening was better than targeted screening. I think that really reinforces the new guidelines and supports them.”

Reference

1. Haukoos J, Rothman RE, Galbraith JW, et al. Hepatitis C screening in emergency departments: the DETECT Hep C randomized clinical trial. JAMA. Published online July 9, 2025. doi:10.1001/jama.2025.10563