SUPPLEMENTARY INFORMATION:

CDC announces a convening to discuss hepatitis C diagnostics. Interested parties are invited to provide public comment on regulations.gov in Docket CDC-2025-0002 on or before February 19, 2025.

Background

More than 2.4 million adults in the United States are estimated to have hepatitis C virus (HCV) infection [Eric H, Hepatology 2024]. New infections continue to increase, primarily in association with injection drug use; nearly 67,400 cases of acute hepatitis C are estimated to have occurred in 2022 [CDC 2022 VH Surv Rpt]. More than half of new infections progress to chronic infection [Seo S, Clin Gastro Hepatol 2020]. Without treatment, HCV infection can lead to advanced liver disease, liver cancer, and death [Liang TF, Ann Intern Med 2000]. Since 2013, safe and effective treatment has been available that cures more than 95% of all treated persons, prevents future health complications, stops further transmission, and allows for the possibility of hepatitis C elimination [Falade-Nwulia O, Ann Intern Med 2017].

Testing is the first step to accessing life-saving treatment; however, about one-third of people with hepatitis C in the United States are unaware of their infection [Lewis KC, CID 2024]. The Centers for Disease Control and Prevention (CDC) recommends hepatitis C screening for all adults at least once, all pregnant persons during every pregnancy, and all persons with risk for HCV infection, including periodic testing if risk persists [Schillie S, MMWR Recomm Rep 2020]. Current testing guidance for clinicians and laboratorians begins with a hepatitis C antibody (anti-HCV) test followed, when reactive, by a nucleic acid test (NAT) to detect HCV RNA to diagnose current infection [CDC MMWR 2013]. Updated operational guidance was provided to ensure completion of the two-step approach using specimens collected during a single patient encounter. (Cartwright EJ, MMWR 2023)

A limitation of the antibody-first hepatitis C testing approach is that it takes an average of 7 to 8 weeks after HCV infection to develop a reactive HCV antibody (Abdel-Hamid M, Clin Micro 2002). Therefore, the current testing sequence fails to diagnose HCV infection in the window-phase/early acute phase, within the first 6 months following infection, and among immunocompromised people who may have delayed seroconversion. Fortunately, advancements in the diagnostic and regulatory landscape have created an opportunity to improve hepatitis C testing. Currently, there are two tests for viral markers that identify current HCV infection: (1) real-time (RT) polymerase chain reaction (PCR) testing of HCV ribonucleic acid (RNA) detects virus within 1 to 2 weeks of infection (Gowda C, Clin Infect Dis 2020); and (2) HCV core antigen (HCVcAg) testing, currently approved outside of the United States, that uses an immunoassay to detect HCV core antigen within 2 to 3 weeks of infection (Sepulveda-Crespo D, Rev Med Virol 2023). Such virologic tests have become faster to perform and more accessible in a variety of care settings including closer to the point-of-care.

With CDC support, the Association of Public Health Laboratories (APHL) held a 2-day convening of key stakeholders and subject matter experts in October 2021 to identify high-priority diagnostic tools needed to advance diagnosis of current HCV infection and linkage to treatment in a range of clinical and nonclinical settings. The published meeting report called for the US Food and Drug Administration (FDA) to reclassify HCV diagnostic tests from class III to class II, supported the availability of an FDA-cleared rapid CLIA-waived point-of-care (POC) HCV viral detection test, and encouraged CDC to review and update recommendations for HCV testing to identify current HCV infection, including testing sequences that detect HCV viral markers in the first step. ( https://www.aphl.org/​aboutAPHL/​publications/​Documents/​ID-HCV-2021-Meeting-Report.pdf).

Subsequent to the APHL-led meeting:

In November 2021, the FDA reclassified hepatitis C diagnostic tests from class III devices to class II devices with special controls (510k), providing a new, lower-barrier opportunity for manufacturers to introduce new hepatitis C diagnostic tools for FDA review, including tests that were available at that time outside of the United States, such as a nucleic acid test (NAT) for HCV RNA detection in a POC format and an assay for HCVcAg. ( printed page 1499)

In January 2024, CDC affirmed existing viral-first testing recommendations among people with recent HCV exposure ( https://www.cdc.gov/​hepatitis-c/​hcp/​diagnosis-testing/​#:~:text=​HCV%20RNA%20testing%20for,a%20syringe%20service%20program);

In January 2024, CDC began the process of updating HCV testing guidance for clinicians and laboratorians, including evaluating testing strategies for the general population that include tests for viral markers in the first testing step ( e.g., “viral-first”); and

In June 2024, the FDA authorized an HCV RNA CLIA-waived near point-of-care test for the diagnosis of current HCV infection.

Public Participation and Public Comment

Public engagement will entail listen-only observation of information shared on day 1 and day 2. If members of the public have input on the questions asked during the meeting, those public comments can be collected through regulations.gov using Docket CDC-2025-0002 on or before February 19, 2025, and will be included in the final meeting report. Written comments must be submitted on or before February 19, 2025.

Please note that comments received, including attachments and other supporting materials, are part of the public record and are subject to public disclosure. Comments will be posted on https://www.regulations.gov. Therefore, do not include any information in your comment or supporting materials that you consider confidential or inappropriate for public disclosure. If you include your name, contact information, or other information that identifies you in the body of your comments, that information will be on public display. CDC will review all submissions and may choose to redact, or withhold, submissions containing private or proprietary information such as Social Security numbers, medical information, inappropriate language, or duplicate/near duplicate examples of a mass-mail campaign. Do not submit comments by email. CDC does not accept comment by email.

90 FR 1497