Nontargeted better than targeted screening at identifying HCV cases in EDs

A non–risk-based screening approach for hepatitis C virus (HCV) infection in the emergency department (ED), where all eligible patients were offered rapid testing, improves the identification of new infections when compared with a targeted approach of narrowly focusing on at-risk groups, according to the DETECT Hep C trial.

Data from three high-volume, geographically diverse, urban EDs in the US showed that the primary outcome of new HCV diagnoses was 34-percent higher with nontargeted vs targeted screening (0.21 percent vs 0.16 percent; relative risk [RR], 1.34, 95 percent confidence interval [CI], 1.05–1.70; p=0.02). [JAMA 2025;doi:10.1001/jama.2025.10563]

The analysis included 147,498 clinically stable adult patients (median age 41 years, 51.5 percent male, 42.3 percent Black). They were randomly assigned to undergo either nontargeted (n=73,847) or targeted (n=73,651) screening, in which HCV testing was offered regardless of risk or based on established risk factors (eg, age, history of drug use, tattoos, piercings, blood transfusion, organ transplant), respectively, as part of ED triage using a structured script and opt-out consent during medical screening.

In the nontargeted screening group, 9,867 patients (59.6 percent) completed testing, resulting in 154 (1.6 percent) new HCV diagnoses (ie, RNA detected). In the targeted screening group, on the other hand, 23,400 patients (31.8 percent) were found to have risk factors for HCV infection and offered testing, with 4,640 (65.2 percent) completing testing and 115 (2.5 percent) receiving new HCV diagnoses.

Compared with targeted screening, nontargeted screening resulted in three times more patients being offered HCV testing (89.0 percent vs 28.5 percent; RR, 3.12, 95 percent CI, 3.09–3.16; p<0.001) and in two times more patients completing the testing (13.4 percent vs 6.3 percent; RR, 2.12, 95 percent CI, 2.05.19; p<0.001).

In terms of outcomes, all patients who received an HCV diagnosis were followed for 18 months. Similar percentages of patients in the nontargeted and targeted screening groups were linked to follow-up care (19.5 percent vs 24.3 percent, respectively; p=0.37), initiated direct-acting antiviral (DAA) treatment (15.6 percent vs 17.4 percent; p=0.74), completed DAA treatment (12.3 percent vs 12.2 percent; p>0.99), and attained sustained virologic response at 12 weeks (9.1 percent vs 9.6 percent; p>0.99).

“To our knowledge, [DETECT Hep C] represents the largest and most comprehensive evaluation of HCV screening strategies in EDs to date and underscores the importance of understanding real-world comparative effectiveness of nontargeted to targeted opt-out HCV screening when integrated into emergency care. This is particularly important given national viral hepatitis elimination goals, which provide a framework to eliminate viral hepatitis as a public health threat in the US,” the investigators said.

They emphasized that the trial included full integration of HCV screening into ED processes of care, 24 hours per day, 7 days per week, while using existing clinical staff. “[The findings support] current recommendations by the CDC, USPSTF, and AASLD-IDSA for performing non–risk-based HCV screening… [as well as] extension of the recommendations specifically to EDs that serve as critical health care access points in the US.” [MMWR Recomm Rep 2020;69:1-17; JAMA 2020;323:970-975; Clin Infect Dis 2023:ciad319; https://www.cdc.gov/nchs/fastats/emergency-department.htm]

HCV identification–treatment gap

However, identifying HCV cases does not always translate to active treatment, noted Dr Preeti Malani from the University of Michigan in Ann Arbor, Michigan, US, and Dr Stephen Schenkel from the University of Maryland School of Medicine in Baltimore, Maryland, US, in an accompanying editorial. [JAMA 2025;doi:10.1001/jama.2025.10868]

“Only 20 percent to 25 percent of patients whose test results were positive for HCV were successfully linked to care and even fewer initiated therapy. This is arguably the most provocative result of the DETECT Hep C trial and strongly suggests a challenge not just in case finding but also in transition from case finding to treatment,” Malani and Schenkel said.

The duo contemplated whether the difficulty in linking patients to care is an inherent consequence of screening in the ED, where an HCV test is often an unexpected addition to a visit made for an entirely different concern.

“Although the ED is held up as a convenient location for screening—perhaps because that is where the patients are and where blood can be drawn—the results of [DETECT Hep C] prompt rethinking of this assumption,” Malani and Schenkel said.

“If testing must be done with the imprimatur of health care, why not test family and friends in the waiting room or even the hospital cafeteria? If offered in such settings, might there be greater commitment on the part of the recipient and therefore a higher likelihood for follow-up care? If the work can be moved to the cafeteria, perhaps then it can also be moved to pharmacies or the local convenience store?,” they asked.

Ultimately, the DETECT Hep C trial may not be merely about optimizing HCV screening but rather offers a roadmap for future public health interventions and follow-up research, according to Malani and Schenkel. “In this game of inches, identifying people with HCV infection is only the first step.”