Nontargeted Emergency Department HCV Screening Could Aid Infection Identification

A nontargeted hepatitis C virus (HCV) screening approach may be preferable to targeted screening for identifying new HCV infections in emergency departments (EDs), according to findings from the DETECT Hep C Trial.1

Coined as the largest pragmatic clinical trial of HCV screening in EDs to date, the trial was conducted in 3 high-volume EDs at Denver Health Medical Center, Johns Hopkins Hospital, and the University of Mississippi Medical Center and found nontargeted HCV screening identified significantly more new diagnoses of HCV infection than targeted screening. Of note, clinician referral from the ED resulted in relatively small proportions of patients who were successfully linked to care, initiated treatment, completed treatment, or attained sustained virologic response at 12 weeks (SVR12).1

“To our knowledge, this trial 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,” Jason Haukoos, MD, MSc, a professor of emergency medicine and Director of Emergency Medicine Research at the University of Colorado Anschutz Medical Campus, and colleagues wrote.1

According to the World Health Organization (WHO), globally, an estimated 50 million people have chronic HCV infection, with about 1 million new infections occurring per year. With the availability of short-course oral, curative pangenotypic HCV direct acting antiviral treatment regimens, the WHO recommends that testing, care and treatment for persons with chronic hepatitis C infection can be provided by trained non-specialist doctors and nurses, using simplified service delivery that includes decentralization, integration, and task shifting, which can be done in primary care, harm reduction services, and prisons. Recently, EDs have become a focus of screening efforts because they serve large numbers of at-risk patients who commonly do not access health care elsewhere.1,2

To compare the effectiveness of targeted and nontargeted HCV screening in EDs, investigators conducted a multicenter, prospective, pragmatic, 2–parallel group randomized clinical trial enrolling patients ≥ 18 years of age who provided consent, did not have critical illness, and had not been previously diagnosed with HCV. Participants were randomly assigned to undergo nontargeted screening, in which HCV testing was offered regardless of risk, or targeted screening, in which testing was offered based on risk assessment using the following criteria: born between 1945 and 1965, IDU, intranasal drug use, tattoo or piercing in an unregulated setting, or blood transfusion or organ transplant before 1992.1

Randomization occurred from November 2019, through August 2022 and was integrated into the electronic health record (EHR) system at each institution using a computer-generated random number algorithm developed and validated at each site prior to beginning enrollment.1

The primary outcome was newly diagnosed HCV infection. Secondary outcomes included repeat HCV diagnoses; HCV test offer, acceptance, and completion; HCV genotype and fibrosis staging; components of the HCV care continuum; and all-cause mortality through 18 months of follow-up.1

A total of 147,498 patient visits were randomized. Among the cohort, the median age was 41 (interquartile range [IQR], 29-57) years, 51.5% of patients were male, and 42.3% were Black.1

Of these, 73,847 patients underwent nontargeted screening, resulting in 9867 (13.4%) tested for HCV and 154 new HCV diagnoses, whereas 73,651 patients underwent targeted screening and 23,400 (31.8%) were identified as having risk factors for HCV infection, resulting in 4640 (6.3%) patients tested for HCV and 115 (2.5%) new HCV diagnoses.1

The prevalence of new HCV diagnoses in the nontargeted and targeted screening groups were 0.21% and 0.16% (difference, 0.05%; 95% CI, 0.01%-0.1%), respectively. Upon analysis, nontargeted screening was associated with a significantly greater number of new HCV diagnoses (relative risk, 1.34; 95% CI, 1.05-1.70; P = .02).1

Despite nontargeted screening identifying more HCV infections, investigators noted small proportions of patients from both the nontargeted and targeted screening groups were linked to follow-up care (19.5% vs 24.3%, respectively), initiated direct-acting antiviral (DAA) treatment (15.6% vs 17.4%), completed DAA treatment (12.3% vs 12.2%), and attained SVR12 (9.1% vs 9.6%).1

“This multicenter randomized clinical trial determined a nontargeted screening approach was superior to targeted screening for identifying new HCV infections among patients seen in 3 urban EDs,” investigators concluded.1 “The substantial decrease in patients who went from diagnosis to SVR12 highlights an urgent need for innovative models of HCV treatment.”

References

1. Haukoos J, Rothman RE, Galbraith JW, et al. Hepatitis C Screening in Emergency Departments: The DETECT Hep C Randomized Clinical Trial. JAMA. doi:10.1001/jama.2025.10563

2. World Health Organization. Hepatitis C. Newsroom. April 9, 2024. Accessed July 10, 2025. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c