From Pathogen to Infectious Disease Diagnosis: Reflex Testing Targets Hepatitis D Gap

This is the latest episode of our From Pathogen to Infectious Disease Diagnosis podcast.

Fewer than 20% of patients in the US who are positive for hepatitis B surface antigen (HBsAg) are tested for hepatitis D virus (HDV), even though an estimated 70,000 to 150,000 people nationwide live with active infection.¹˒² To narrow the gap, Labcorp added a hepatitis D reflex testing option to its Comprehensive Hepatitis Testing portfolio in August 2026. When a clinician selects the option, the laboratory automatically runs HDV testing on the original blood sample whenever HBsAg is detected, according to the company.¹

The launch follows the FDA’s May 22, accelerated approval of bulevirtide-gmod (Hepcludex; Gilead Sciences), the first US treatment for chronic HDV infection.³ Charles M. Walworth, MD, associate vice president of medical affairs and education and co-discipline director for molecular infectious diseases at Labcorp, joined host Rodney E. Rohde, PhD, SV/SM/MB(ASCP)CM, FACSc, to discuss how the pathway works and why HDV diagnosis has lagged.

Walworth attributes the gap to several factors. For years, HDV testing was not widely available, and clinicians had little reason to diagnose an infection treatable only with pegylated interferon alfa, an option he describes as unpopular with patients and clinicians because of low response rates and a heavy adverse event burden. In a retrospective Labcorp analysis spanning 2024 through August 2026, only 8.3% of HBsAg-positive patients were screened for HDV, he says, although month-over-month utilization is rising.

Workflow compounds the problem. Under a standard pathway, an HBsAg-positive patient returns for HDV antibody testing and then again for HDV RNA confirmation, and each added visit raises the risk of loss to follow-up, Walworth notes.

Three Reflex Pathways From HBsAg Screening to HDV RNA Confirmation

Labcorp offers three reflex options, Walworth explains. A positive HBsAg result on the recommended hepatitis B triple panel (surface antigen, surface antibody, and core antibody) reflexes automatically to HDV antibody testing, as does a positive result on a standalone qualitative HBsAg test. For patients with a known hepatitis B diagnosis, an HDV antibody order reflexes to quantitative HDV RNA PCR.

Interpretation parallels hepatitis C, he says. The HDV antibody assay reports a combined IgG/IgM result as reactive or nonreactive and indicates exposure only, whereas any detectable HDV RNA signals active infection. Only qualitative HBsAg testing feeds the reflex pathway; the quantitative HBsAg assay remains a standalone test.

The model draws on Labcorp’s hepatitis C experience. Investigators, including Walworth, reviewed more than 38 million HCV antibody specimens tested from 2018 to 2024, with the full analysis published in Clinical Infectious Diseases in April 2026.⁴ Same-day HCV RNA testing on antibody-positive samples rose from 38.0% in 2018 to 82.2% in 2024, while follow-up RNA testing averaged 46.8% when clinicians ordered standalone antibody tests.⁴

Earlier detection matters most in superinfection, which Walworth says progresses rapidly toward cirrhosis, liver failure, and hepatocellular carcinoma. Undiagnosed patients also continue to transmit HBV and HDV through blood, body fluids, and sexual contact. He reflects on past patients who might have been coinfected, but the testing was unavailable to confirm it.

“I look back when I was in clinical practice, and this was more than 15 years ago, where I had those hepatitis B patients who really made the lifestyle modifications. …They stopped drinking alcohol. They stopped injecting drugs. They stopped taking toxic medications. Yet they seemed to progress more rapidly than they should have,” Walworth said. “There was no opportunity for hepatitis D testing back then…And I think to myself, how many of them could have been co-infected?”

Guidelines remain a barrier. The American Association for the Study of Liver Diseases (AASLD) guidance, last updated in 2018, uses a risk-based approach, whereas the European Association for the Study of the Liver recommends universal HDV testing, Walworth notes. Of three clinical sites he recently canvassed in New York City, Chicago, and Orange County, California, none had implemented an HDV testing algorithm, and one was waiting for formal guideline recommendations.

“What we want to do is streamline [hepatitis D] testing, and we want to really cut down on the number of visits and get patients into care as soon as possible,” Walworth said.

References

1. Labcorp. Labcorp launches hepatitis D reflex testing to enable earlier detection of the most severe form of viral hepatitis. Published August 25, 2026. Accessed November 2, 2026. [URL]

2. Gish RG. Delta hepatitis in the United States: epidemiology, testing, and linkage to care. Gastroenterol Hepatol (N Y). 2023;19(10).

3. US Food and Drug Administration. FDA approves first treatment for chronic hepatitis delta virus (HDV) infection. Published May 22, 2026. Accessed November 2, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-chronic-hepatitis-delta-virus-hdv-infection

4. Lee MK, Walworth CM, Alfego D, Gillim L. P-1826. Trends in hepatitis C virus laboratory testing in a large, U.S. commercial laboratory, 2018-2024. Open Forum Infect Dis. 2026;13(suppl). doi:10.1093/ofid/ofaf695.1995