Epidemiological Burden of Hepatitis Delta Virus in the United States

ABSTRACT Hepatitis D virus (HDV) affects nearly 5% of people globally who are chronically infected with hepatitis B virus, according to the World Health Organisation. The prevalence of HDV in the United States is considered lower than in other countries. However, HDV seroprevalence studies of the US population are limited, and reported seroprevalences vary. To improve diagnoses, universal HDV testing of hepatitis B surface antigen (HBsAg)‐positive specimens has been proposed. The objective of this study was to estimate the prevalence of HDV infection within the United States in HBsAg‐positive specimens. Unique deidentified remnant HBsAg‐positive specimens submitted for routine clinical testing to Quest Diagnostics, representing all 10 Health and Human Services (HHS) regions, were included. Reflex testing of HBsAg‐positive specimens for HDV antibody testing, and further testing of positive specimens for HDV RNA, was conducted from July 2023 to June 2024 for 5251 HBsAg‐positive specimens. The cohort was 45% female, with mean ages of 50.8 (M) and 49.4 (F) years. The seroprevalence of anti‐HDV was 2.2% [95% CI: 1.8%–2.6%; range: 2.5%–4.1%]. Of 107 anti‐HDV‐positive specimens, 28% were positive for HDV RNA (viral load range: 94–7,480,000 IU/mL: n = 23; Detected < 40 IU/mL: n = 7). This is the first nationwide seroprevalence study examining HBsAg‐positive samples collected from 10 HHS regions across the United States, which offers an overview of the prevalence of HDV in the United States through the use of HbsAg‐positive remnant specimens in proportion to regional population sizes. Expanded screening for HDV would help identify patients who may benefit from HDV‐related interventions.