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.
Hepatitis delta virus (HDV) has been detected in the minor salivary gland (MSG) tissue of Sjögren’s disease (SjD) patients in the absence of a hepatitis B virus (HBV) coinfection. Previous research has shown that HDV antigen (HDAg) expression can trigger an SjD-like phenotype in vivo, demonstrating a potential cause-and-effect relationship. We hypothesize that if HDV plays a role in the development of SjD, then HDV profiles may be correlated with disease manifestations. This retrospective study characterized HDV in a cohort of 48 SjD MSG samples collected between 2014 and 2021. Analyses of HDAg expression, including cell type and subcellular localization, in situ hybridization of HDV RNA, and comparative analyses with associated SjD and viral hepatitis clinical features, were conducted. HDAg was detected in MSG acinar, ductal, myoepithelial, and adipose cells and localized with the nuclei, cytoplasm, and mitochondria. In situ hybridization detected HDV genomic RNA localization in the MSG nuclei. A significant negative correlation was found between HDAg intensity and focal lymphocytic inflammation and in patients with both anti-SSA/Ro-52 and anti-SSA/Ro-60. In analyzing autoimmune disease comorbidities with SjD, it was found that SjD patients diagnosed with autoimmune thyroiditis and/or hypothyroidism were significantly more represented in the high HDAg intensity group compared to the negative and moderate HDAg intensity groups. No significant associations were detected between MSG-localized HDAg and liver enzymes or an evident HBV coinfection. This study has further confirmed that there is a nonhepatic reservoir for chronic HDV persistence in SjD-affected salivary gland tissue in a third independent SjD patient cohort. In addition, this study describes the unique colocalization of HDAg with mitochondria. The detection of HDV antigen and sequence within SjD-affected salivary gland tissue, and in the absence of an evident current or past HBV coinfection, warrants further investigation.
Background Dry mouth currently affects roughly 20% of the population and is a condition characterized by chronic hyposalivation and/or subjective reports of xerostomia. Low saliva flow can be indicative of other undiagnosed diseases, such as primary Sjogren’s syndrome, and may contribute to difficulty chewing, increased caries susceptibility and infection. The passive drool test (PDT) is the primary method used to evaluate patients for hyposalivation but it is time-consuming and inconvenient. New methodology is needed to facilitate increased testing for hyposalivation in the dental clinic. The aim of this study was to evaluate an alternative method to measure salivary flow in dental offices. Methods In this study, we tested a new biomedical device, the BokaFlo™, to measure salivary flow in subjects in comparison to the current PDT standard. Participants completed an oral health questionnaire and saliva flow was evaluated by the PDT and the BokaFlo™ system. Results Saliva flow as measured by the BokaFlo™ positively correlated with the saliva flow measured by the PDT methodology (r = 0.22, p < 0.05). The device predicted low saliva flow in subjects with a sensitivity of 0.76 and specificity of 0.84 for subjects with hyposalivation, defined as a saliva flow rate of ≤ 0.1 ml/min. A significant negative correlation between the total oral health questionnaire score and the likelihood of participant exhibiting low salivary flow was observed (r = − 0.31, p < 0.006). Conclusion The BokaFlo™ was effectively able to measure low saliva flow correlating with the PDT methodology and may provide more efficient testing of saliva flow in the dental office.
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.
The international incidence of Hepatitis Delta Virus (HDV) is challenging to accurately estimate due to the 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 global HDV diagnoses datasets. Publicly accessible datasets containing yearly incidence for HDV and Hepatitis B Virus (HBV) diagnoses were identified for Argentina, Australia, Austria, Brazil, Bulgaria, Canada, Finland, Germany, Macao, Netherlands, New Zealand, Norway, Sweden, Taiwan, Thailand, United Kingdom, and United States. 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). Additionally, analyses of available demographic data identified a decreasing trend of HDV diagnoses in patients 0-19 years of age and an increasing trend of HDV diagnoses in patients ≥60 years of age. 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 observed international shifts in HDV incidence.
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