Hepatitis D virus (HDV) is a rare co-infection with hepatitis B virus. Currently, HDV is not a nationally notifiable disease in the United States. Only 55% of states and territories require HDV reporting, and most lack defined case definitions. Standardization of reporting requirements is crucial for monitoring HDV epidemiology.

BACKGROUND:This study assessed the epidemiology of hepatitis delta virus (HDV) within the University of Utah UHealth health care system (2000-2021). METHODS:Analysis of HDV/HBV testing, diagnostic codes, liver enzymes, and comorbidities was performed. RESULTS:Among the 1962 HBV patients, only 22.2% underwent HDV testing, revealing an 8.3% positivity rate for HDV coinfections. This study observed a consistent increase in HBV and HDV cases, with higher HDV detection rates linked to increased testing. Limited HDV testing and potential screening biases were evident. DISCUSSION:Improved HDV testing and surveillance are crucial for early detection and implementation of targeted therapies.

The international epidemiology of Hepatitis Delta Virus (HDV) is challenging to accurately estimate due to limited active surveillance for this rare infectious disease. Prior HDV epidemiological studies have relied on meta-analysis of aggregated and static datasets. These limitations restrict the capacity to actively detect low-level and/or geographically dispersed changes in the incidence of HDV diagnoses. This study was designed to provide a resource to track and analyze the international HDV epidemiology. Datasets analyzed collectively consisted of >700,000 HBV and >9,000 HDV reported cases ranging between 1999-2020. Datasets mined from government publications were identified for Argentina, Australia, Austria, Brazil, Bulgaria, Canada, Finland, Germany, Macao, Netherlands, New Zealand, Norway, Sweden, Taiwan, Thailand, United Kingdom, and United States. Time series analyses, including Mann-Kendall (MK) trend test, Bayesian Information Criterion (BIC), and hierarchal clustering, were performed to characterize trends in the HDV timelines. An aggregated prevalence of 2,560 HDV/HBV100,000 cases (95% CI 180-4940) or 2.56% HDV/HBV cases was identified, ranging from 0.26% in Canada to 20% in the United States. Structural breaks in the timeline of HDV incidence were identified in 2002, 2012, and 2017, with a significant increase occurring between 2013-2017. Significant increasing trends in reported HDV and HBV cases were observed in 47% and 24% of datasets, respectively. Analyses of the HDV incidence timeline identified four distinct temporal clusters, including Cluster I (Macao, Taiwan), Cluster II (Argentina, Brazil, Germany, Thailand), Cluster III (Bulgaria, Netherlands, New Zealand, United Kingdom, United States) and Cluster IV (Australia, Austria, Canada, Finland, Norway, Sweden). Tracking of HDV and HBV cases on an international scale is essential in defining the global impact of viral hepatitis. Significant disruptions of HDV and HBV epidemiology have been identified. Increased surveillance of HDV is warranted to further define the etiology of the recent breakpoints in the international HDV incidence.

Abstract Background Hepatitis Delta Virus (HDV) is a rare infectious disease that requires a helper virus (ex. Hepatitis B Virus (HBV)) for transmission. Worldwide, it is estimated that 12-72 million individuals are infected with HDV. Within the United States, an accurate measure of HDV prevalence is attenuated by limited testing and variable notifiable disease status. Recent reports have noted a significant shift in the international HDV epidemiology. This retrospective study was designed to further evaluate the prevalence and clinical features of HDV and HBV within the Utahn patient population. Methods Within University of Utah Health, patient demographics, diagnostic codes (ICD9, ICD10) for HBV and HDV, CPT test codes and lab results were evaluated from 2000-2020. Univariate and multivariate analyses were performed. Timeseries analyses, including Mann-Kendall (MK) trend test, Bayesian Information Criterion (BIC) and Autoregressive Integrated Moving Average (ARIMA) were performed to characterize trends in HDV and HBV prevalence. Results Between 2000-2020, 2878 HBV and 180 HDV patients were identified within the University of Utah Health system. The median age of the HBV and HDV patients was 45 years with 56% males and 42 years with 60% males, respectively. 10% of all HBV-tested patients were tested for HDV. The positivity rate of patients tested for HDV was 7%. Statistical analysis of race and ethnicity showed a significant difference in incidence and testing rates among the Utahn Asian population when compared against non-Asian populations. A significant increasing trend in the incidence of both HBV (MK=156, p=2.8e-6) and HDV (MK=83, p=0.01) was observed between 2000-2020. Within the timeframe analyzed, two structural breaks were observed for HDV/HBV incidence ratio. Conclusion Together, our analysis suggests a significant change in the incidence of HDV and, due to the global temporal trend observed, may be suggestive of a change in HDV transmission pattern. Active surveillance of HDV in the United States and worldwide is warranted to further define these observed changes in HDV incidence. Disclosures All Authors: No reported disclosures.

AbstractHepatitis delta virus (HDV) has been detected in the minor salivary gland (MSG) tissue of Sjogren’s Syndrome (SjS) patients in the absence of an HBV co-infection. HDV antigen expression was previously shown to trigger an SjS-like phenotype in vivo, demonstrating a cause-and-effect association. We hypothesize that if HDV regulates SjS development, then HDV profiles may correlate with disease manifestations. This retrospective study characterized HDV in a cohort of 48 SjS MSG between 2014-2021. Analyses of HDV antigen (HDAg) expression, including cell type and subcellular localization,in situhybridization of HDV RNA, and comparative analyses with associated SjS and viral hepatitis clinical features were conducted. HDAg was detected in MSG acinar, ductal, and adipose cells. HDAg localized with nuclei and mitochondria. HDV genomic RNA localized to the nucleus. A significant negative correlation was noted between HDAg intensity and focal lymphocytic inflammation. No significant associations were detected between MSG-localized HDAg and liver enzymes, or an evident HBV co-infection. This study has identified a non-hepatic reservoir for chronic HDV persistence in SjS-affected MSG and a unique mitochondrial localization for HDV antigen. Detection of non-hepatic HDV-mediated disease in the absence of an evident current or past HBV co-infection warrants further investigation.

Hepatitis delta virus (HDV) has been detected in the minor salivary gland (MSG) tissue of Sjogren’s Syndrome (SjS) patients in the absence of an HBV co-infection. HDV antigen expression was previously shown to trigger an SjS-like phenotype in vivo, demonstrating a cause-and-effect association. We hypothesize that if HDV regulates SjS development, then HDV profiles may correlate with disease manifestations. This retrospective study characterized HDV in a cohort of 48 SjS MSG between 2014-2021. Analyses of HDV antigen (HDAg) expression, including cell type and subcellular localization, in situ hybridization of HDV RNA, and comparative analyses with associated SjS and viral hepatitis clinical features were conducted. HDAg was detected in MSG acinar, ductal, and adipose cells. HDAg localized with nuclei and mitochondria. HDV genomic RNA localized to the nucleus. A significant negative correlation was noted between HDAg intensity and focal lymphocytic inflammation. No significant associations were detected between MSG-localized HDAg and liver enzymes, or an evident HBV co-infection. This study has identified a non-hepatic reservoir for chronic HDV persistence in SjS-affected MSG and a unique mitochondrial localization for HDV antigen. Detection of non-hepatic HDV-mediated disease in the absence of an evident current or past HBV co-infection warrants further investigation.### Competing Interest StatementThe authors have declared no competing interest.

ABSTRACT Background & Aims The international incidence of Hepatitis Delta Virus (HDV) is challenging to accurately estimate due to limited testing and lack of active surveillance for this rare infectious disease. These limitations prevent the detection of low-level and/or geographically dispersed changes in the incidence of HDV diagnoses. A study was designed to enable international active tracking and analyses of HDV epidemiology by aggregating international HDV and Hepatitis B Virus (HBV) diagnoses datasets. Methods Publicly accessible datasets containing yearly incidence for HDV and HBV diagnoses were mined from government publications for Argentina, Australia, Austria, Brazil, Bulgaria, Canada, Finland, Germany, Macao, Netherlands, New Zealand, Norway, Sweden, Taiwan, Thailand, United Kingdom, and United States. The Bayesian Information Criterion (BIC) was used to determine the best-fitting breakpoint model for the number of breakpoints and the break dates identified using the determined model. Results Aggregated analysis of these HDV and HBV datasets spanning 1999-2020 identified structural breaks in the timeline of HDV incidence in 2002, 2012, and 2017. A significant increase in the international HDV incidence, relative to reported HBV diagnoses, occurred in 2013-2017. Secondary analysis identified four distinct temporal clusters of HDV incidence, including Cluster I (Macao, Taiwan), Cluster II (Argentina, Brazil, Germany, Thailand), Cluster III (Bulgaria, Netherlands, New Zealand, United Kingdom, United States), and Cluster IV (Australia, Austria, Canada, Finland, Norway, Sweden). Conclusion Re-evaluation of the testing paradigm for HDV in HBV-positive patients and an active surveillance status of HDV are warranted to define the etiology of the structural breaks in HDV incidence timelines.