High Prevalence of Cirrhosis or Hepatocellular Carcinoma at Hepatitis Delta Infection Diagnosis Reflects Alarming Delays in Testing

Delays in timely diagnosis and treatment of hepatitis delta virus (HDV) contribute to more severe liver disease at presentation. We aim to evaluate the prevalence and predictors of advanced liver disease at presentation among a national cohort of United States (U.S.) Veterans co-infected with chronic hepatitis B (CHB) and HDV. We retrospectively evaluated all U.S. Veterans with chronic HBV from 1/1/2010 to 12/31/2024 who underwent anti-HDV testing to evaluate the proportion who had advanced liver disease (cirrhosis, cirrhosis-related complications and hepatocellular carcinoma) at the time of HDV diagnosis. We performed sensitivity analyses among those who completed HDV RNA testing. Prevalence of advanced liver disease at the time of HDV testing was compared between anti-HDV positive and negative and among subgroups using chi-square testing. Among 29,061 chronic HBV patients, we identified 3558 patients who completed HDV testing during the study period, among whom 108 (3.0%) were anti-HDV positive and 3450 (97.0%) were anti-HDV negative. Anti-HDV positive patients had a significantly greater proportion of advanced liver disease compared to those who were anti-HDV negative (32.4% vs. 15.2%, p < 0.0001). Sensitivity analyses among patients who completed HDV RNA testing demonstrated similar trends of advanced liver disease (45.5% in HDV RNA positive vs. 18.6% in HDV RNA neg, p < 0.001). Among a national cohort of U.S. Veterans with chronic HBV, nearly 1 in 3 had already developed advanced liver disease at the time of HDV diagnosis, reflecting dangerous delays in diagnosis and treatment. Implementing effective programmes (e.g., reflex testing) to improve timely HDV diagnosis and treatment is urgently needed to prevent liver-related morbidity and mortality.