Optimizing hepatitis C virus testing in the era of point-of-care RNA diagnostics.

Major advances in hepatitis C virus (HCV) treatment have made timely and accurate diagnosis a critical determinant for United States elimination goals. Recently authorized point-of-care (POC) HCV RNA testing enables faster diagnosis than the traditional two-step algorithm but comes with higher laboratory costs. We analyzed HCV testing data from 2017 to 2024 across three medical centers in Seattle, Washington, to evaluate strategies for integrating new rapid direct detection tests. HCV antibody testing volumes increased 72% over the study period, with outpatient settings accounting for 76.0% of tests and a 2.7% positivity rate. Emergency department testing increased by 682% to 5,654 tests in 2024, with a 10.3% positivity rate, such that one-third of all HCV diagnoses in our medical system now originate from the public county hospital emergency department. Adoption of sample-to-answer HCV RNA testing in 2024 reduced median collection-to-result turnaround times for antibody-positive specimens from 84 h (IQR 58-120) to 45 h (IQR 28-57). Using a viral load cut-off of 10,000 IU/mL, HCV antigen testing was estimated to detect 98% of infections. Converting all HCV testing to POC RNA would increase laboratory costs by 260% (+$6,439 per HCV infection detected), while restricting POC RNA to the public county hospital emergency department would increase costs by 22.3% (+$552 per HCV infection detected). Reflexing antibody-positive samples to antigen testing slightly reduced costs. These findings highlight the significant laboratory costs associated with POC HCV RNA testing and the need for specific reimbursement and funding mechanisms for new HCV testing algorithms.IMPORTANCEHepatitis C virus (HCV) elimination in the United States requires rapid and reliable diagnosis, yet current testing pathways are too slow for treatment initiation in a single clinical visit. Analysis of more than 325,000 HCV test results from 2017 to 2024 from our academic medical system in Seattle, Washington, highlights the growing role of emergency departments, particularly those serving safety-net populations, in making new HCV diagnoses. While point-of-care HCV RNA testing can enable connection to treatment, it substantially increases laboratory costs when implemented broadly. Targeted use of point-of-care HCV RNA in high-yield settings such as safety-net emergency departments is essential to maximize public health impact while preserving laboratory resources. These findings highlight the need for policy and reimbursement frameworks that support cost-effective deployment of new HCV diagnostic technologies.