Delta Virus Infection Research Articles

FRI-199 - Hepatitis delta virus infection in Turkey: A meta analysis of prevalence

FRI-199 - Hepatitis delta virus infection in Turkey: A meta analysis of prevalence

WED-185 - Predominance of genotype 5 hepatitis delta virus infection in a Portuguese centre

WED-185 - Predominance of genotype 5 hepatitis delta virus infection in a Portuguese centre

WED-116 - A retrospective observational cohort study of liver-related events among individuals with hepatitis B virus infection with and without hepatitis delta virus infection

WED-116 - A retrospective observational cohort study of liver-related events among individuals with hepatitis B virus infection with and without hepatitis delta virus infection

WED-134 - Hepatitis delta treatment utilization in the United States: an analysis of commercially insured adults with hepatitis delta virus infection

WED-134 - Hepatitis delta treatment utilization in the United States: an analysis of commercially insured adults with hepatitis delta virus infection

WED-160 - Healthcare resource use and costs associated with hepatitis delta virus infection compared to hepatitis B virus monoinfection among commercially insured patients in the US

WED-160 - Healthcare resource use and costs associated with hepatitis delta virus infection compared to hepatitis B virus monoinfection among commercially insured patients in the US

FRI-152 - Qualitative interviews to assess the impact of chronic hepatitis delta virus infection on health-related quality of life in untreated patients from the US, Italy, Spain, and Germany

FRI-152 - Qualitative interviews to assess the impact of chronic hepatitis delta virus infection on health-related quality of life in untreated patients from the US, Italy, Spain, and Germany

Elimination of HDV: Epidemiologic implications and public health perspectives.

Hepatitis delta virus (HDV) infection causes the severest form of viral hepatitis in humans. Discovered in 1977, it was considered an infection prevalent in the eastern Mediterranean region. Today it is recognized as a global infection of public health importance, however accurate prevalence remains uncertain because of lack of good epidemiological studies. Under-screening for HDV is the single most important factor in under-estimating the true burden of infection. Urgent efforts are therefore needed to apply reliable screening tools and robust surveillance methodologies to study HDV. There is now a move by major hepatology societies to recommend HDV antibody testing in all persons with HBV infection. Important differences also need to be recognized between countries considered endemic or non-endemic countries. While the endemic infections likely spread horizontally in the general population, and is quite often nosocomial, in non-endemic countries special populations may carry the greater burden, such as persons with injection drug use and various sexual exposures. Even in endemic countries, HDV often exists in significant pockets of the general population. HDV has been categorized as an orphan infection due to lack of approved therapies. Recently there have significant advances in therapy and further clinical trials continue. However, as new therapies are approved, equitable access to the medications will become a major public health issue, particularly because most HDV patients live in low or low middle income countries.

Distinct histological patterns in chronic hepatitis D with nucleos(t)ide analogue therapy.

Chronic hepatitis delta virus (HDV) infection leads to a more severe hepatitis than hepatitis B virus (HBV) infection alone. Specific histological staining patterns have been described in HBV mono-infection, however this has not been extensively investigated in HDV co-infection. This study evaluated whether the use of nucleos(t)ide analogs (NAs) for concurrent HBV infection has an impact on the histological appearance of chronic HDV. Liver biopsies of all patients referred for management of HDV infection were reviewed and hepatitis-specific stains for HBV antigens were evaluated. Clinical and histological characteristics were compared between patients on and off-NA therapy. 50 patients were included in our analysis, of which 26 (52%) were on NA therapy at the time of the biopsy. Overall, 8% stained for HBV core antigen and 86% stained for HBV surface antigen. On and off-NA groups had similar degrees of fibrosis and inflammation, however NA patients had an odds ratio of 7.15 for membranous staining and 0.13 for scattered granular staining (p = 0.001). No association was found with markers of disease severity or viral activity, with nonetheless a lower score of total inflammation noted in biopsies with a positive membranous stain (8.5 vs. 10.3 p = 0.04). In chronic HDV infection, patients treated with nucleos(t)ide analogs demonstrate a unique membranous staining pattern for hepatitis B surface antigen, which is not associated with HBV or HDV replicative activity. These findings may help improve the understanding of the role of HBV directed therapy in HDV pathophysiology. Histological staining is associated with viral activity in chronic HBV, however this has been infrequently explored in HDV. In HDV, staining patterns differ based on HBV treatment status and do not appear to be associated with markers of viral activity.

Hepatitis delta infection among persons living with HIV in Europe.

A high prevalence of hepatitis delta virus (HDV) infection, the most severe form of viral hepatitis, has been reported among persons living with HIV (PLWH) in Europe. We analysed data from a large HIV cohort collaboration to characterize HDV epidemiological trends across Europe, as well as its impact on clinical outcomes. All PLWH with a positive hepatitis B surface antigen (HBsAg) in the Swiss HIV Cohort Study and EuroSIDA between 1988 and 2019 were tested for anti-HDV antibodies and, if positive, for HDV RNA. Demographic and clinical characteristics at initiation of antiretroviral therapy were compared between HDV-positive and HDV-negative individuals using descriptive statistics. The associations between HDV infection and overall mortality, liver-related mortality as well as hepatocellular carcinoma (HCC) were assessed using cumulative incidence plots and cause-specific multivariable Cox regression. Of 2793 HBsAg-positive participants, 1556 (56%) had stored serum available and were included. The prevalence of HDV coinfection was 15.2% (237/1556, 95% confidence interval [CI]: 13.5%-17.1%) and 66% (132/200) of HDV-positive individuals had active HDV replication. Among persons who inject drugs (PWID), the prevalence of HDV coinfection was 50.5% (182/360, 95% CI: 45.3%-55.7%), with similar estimates across Europe, compared to 4.7% (52/1109, 95% CI: 3.5%-5.9%) among other participants. During a median follow-up of 10.8 years (interquartile range 5.6-17.8), 82 (34.6%) HDV-positive and 265 (20.1%) HDV-negative individuals died. 41.5% (34/82) of deaths were liver-related in HDV-positive individuals compared to 17.7% (47/265) in HDV-negative individuals. HDV infection was associated with overall mortality (adjusted hazard ratio 1.6; 95% CI 1.2-2.1), liver-related death (2.9, 1.6-5.0) and HCC (6.3, 2.5-16.0). We found a very high prevalence of hepatitis delta among PWID across Europe. Among PLWH who do not inject drugs, the prevalence was similar to that reported from populations without HIV. HDV coinfection was associated with liver-related mortality and HCC incidence.

What does quantitative HBsAg level mean in chronic hepatitis D infection?

In hepatitis delta virus (HDV) infection, which is an important etiological cause of chronic liver disease, the relationship between serum quantitative HBsAg level and fibrosis and histological activity was investigated. Between 2014 and 2020, 98 patients with chronic HDV infection (53 noncirrhotic, 45 cirrhotic) participated in this prospectively designed study. Quantitative HBsAg levels of the patients were measured and their relationship with the stage of chronic liver disease was compared with histological activity index (HAI), fibrosis score and HDV RNA, model for end-stage liver disease score and other biochemical parameters. All patients were infected with genotype 1 (100%). HBeAg was positive in 8 (8.1%) of the patients. A correlation was found between quantitative HBsAg level and HDV RNA level in patients with both cirrhotic (r = 0.568; P < 0.001) and noncirrhotic (r = 0.644; P < 0.001) HDV infection. Alanine transaminase (P = 0.001; r = 0.495) and aspartate transaminase (P = 0.001; r = 0.511) levels correlated with quantitative HBsAg levels, more prominently in noncirrhotic patients. There was a correlation between quantitative HBsAg level and histological activity index (HAI) in patients with noncirrhotic HDV infection (P < 0.001; r = 0.664). In receiver operating characteristic analysis, both quantitative HBsAg (for cutoff: 1000; sensitivity 76%; specificity 17%; P = 0.335) and HDV RNA (for cutoff: 100000; sensitivity 2%; specificity 98%; P = 0.096) were not predictive markers for cirrhosis. Quantitative HBsAg level can be evaluated as an indicator of viral replication and histological activity in patients with chronic delta hepatitis without cirrhosis. We think that quantitative HBsAg level will be useful in the management of chronic HDV infection, especially in noncirrhotic patients.

Long-term trends of alanine aminotransferase levels among persons living with human immunodeficiency virus/hepatitis B virus with and without hepatitis delta coinfection

BackgroundHepatitis delta virus (HDV) infection accelerates the progression of liver disease in persons living with HIV and hepatitis B virus (HBV) coinfection. We explored the association between HDV infection and alanine aminotransferase (ALT) elevation during tenofovir-containing antiretroviral treatment among persons living with HIV/HBV.Materials and methodsWe included persons living with HIV/HBV with and without HDV starting tenofovir-containing antiretroviral therapy (ART) in three European cohorts with at least 18 months of follow-up. We defined HDV infection as a positive anti-HDV antibody test. We assessed risk factors for ALT elevation ≥ 1.25x upper limit of normal after 5 years of tenofovir-treatment using multivariate logistic regression models. The difference in ALT trends between individuals with and without HDV was evaluated using linear mixed effects models.Results61/518 (11.8%) participants had an HDV infection. Among individuals with HDV, 63.9% had ALT elevation after 2 years and 55.6% after 5 years of tenofovir, whereas the estimates were 34.1% after two and 27.0% after 5 years in those without HDV. HDV coinfection (adjusted odds ratio 2.8, 95% confidence interval 1.4–5.8) and obesity at baseline (adjusted odds ratio 3.2, 95% confidence interval 1.2–8.0) were associated with ALT elevation after 5 years of tenofovir therapy. Mean ALT levels were consistently higher during follow-up in participants with HDV compared to those without HDV.ConclusionPersistent ALT elevation is common in persons living with HIV/HBV in Europe despite adequate HBV therapy. HDV coinfection and obesity are independent risk factors for persistent ALT elevation during long-term tenofovir treatment.

Shear wave elastography: How well does it perform in chronic hepatitis D virus infection?

Hepatitis delta virus (HDV) infection is associated with accelerated progression of liver disease to cirrhosis. Shear wave elastography (SWE) is a non-invasive evaluation method of liver fibrosis. Its performance in accurately characterizing HDV fibrosis compared to other noninvasive markers remains unknown. We assessed the performance of SWE in patients with chronic HDV, Hepatitis B (HBV) and Hepatitis C (HCV) infection. Cirrhosis was determined by histology or clinical data. Area under receiver operator characteristics (AUROC) was used to assess diagnostic performance in identifying cirrhosis by SWE in comparison with Fibroscan® (VCTE) and serologic tests of fibrosis. 158 patients with chronic hepatitis (HDV:44%, HBV: 46% and HCV: 29%) were evaluated. Cirrhosis was diagnosed in 28 (17.7%) patients. Mean noninvasive fibrosis measurements for the HBV/HCV and HDV groups, respectively, were as follows: APRI: 0.73 ± 1.08 and 1.3 ± 1.38; FIB-4: 1.90 ± 2.24 and 2.33 ± 2.24; VCTE: 8.9 ± 6.7kPa vs 10.4 ± 5.3kPa; SWE: 1.5 ± 0.2m/s and 1.6 ± 0.2m/s. The performance of SWE in detecting HDV-induced cirrhosis (AUROC 0.84, 95% CI 0.71-0.97) was slightly lower than in HBV/HCV induced disease (AUROC 0.88, 95% CI 0.81-0.96). For HDV patients, the performance of SWE was comparable to VCTE and slightly better than APRI and FIB-4 especially in APRI and FIB-4 indeterminate zones. The overall less accurate performance of noninvasive markers in HDV in comparison with HBV and HCV may be a result of significant hepatic inflammation in HDV.

Real‐life experiences with bulevirtide for the treatment of hepatitis delta—48 weeks data from a German centre

In July 2020, the entry inhibitor bulevirtide was approved in the European Union for the treatment of chronic hepatitis delta virus (HDV) infection. We describe the first 48 weeks of bulevirtide therapy in eight patients (n= 7 male, n= 1 female; n= 3 compensated cirrhosis) treated at our centre. Median ALT values declined from 82 to 34 U/L after 48 weeks. Median HDV RNA dropped from 13 380 000 to 3135 copies/ml. One patient showed no significant response and was discontinued at week 16. Overall, we observed a favourable safety profile and a marked biochemical and virological response in the majority of our patients.

THU400 - Clinical evidence for unconventional hepatitis delta virus infections in endemic countries

THU400 - Clinical evidence for unconventional hepatitis delta virus infections in endemic countries

Identification of novel antivirals against hepatitis delta virus infection via high throughput screening

Identification of novel antivirals against hepatitis delta virus infection via high throughput screening

THU386 - Hepatitis Delta virus infection in patients with chronic hepatitis B is associated with greater risk of liver disease progression and liver-related mortality: a systematic review and meta-analysis

THU386 - Hepatitis Delta virus infection in patients with chronic hepatitis B is associated with greater risk of liver disease progression and liver-related mortality: a systematic review and meta-analysis

Signature of chronic hepatitis B virus infection in nails and hair

BackgroundHepatitis B virus (HBV) is detected in extrahepatic tissues of individuals with HBV infection. Whether nails and hair contain HBV has been unknown.MethodsWe examined two patient groups: those with chronic HBV infection alone (n = 71), and those with both chronic HBV and hepatitis delta virus (HDV) infections (n = 15). HBV DNA in the patients’ fingernails and hair were measured by real-time PCR. Hepatitis B surface antigen (HBsAg) of fingernails was evaluated by an enzyme immunoassay. HDV RNA in fingernails was measured by real-time PCR. Immunochemical staining was performed on nails. We used chimeric mice with humanized livers to evaluate the infectivity of nails.ResultsOf the 71 pairs of HBV-alone nail and hair samples, 70 (99%) nail and 60 (85%) hair samples were positive for β-actin DNA. Of those 70 nail samples, 65 (93%) were HBV DNA-positive. Of the 60 hair samples, 49 (82%) were HBV DNA-positive. The serum HBV DNA level of the nail HBV DNA-positive patients was significantly higher than that of the nail HBV DNA-negative patients (p < 0.001). The hair HBV DNA-positive patients’ serum HBV DNA level was significantly higher compared to the hair HBV DNA-negative patients (p < 0.001). The nail HBV DNA level was significantly higher than the hair HBV DNA level (p < 0.001). The nails and hair HBV DNA levels were correlated (r = 0.325, p < 0.05). A phylogenetic tree analysis of the complete genome sequence of HBV isolated from nails and hair identified the infection source. Of the 64 nail samples, 38 (59%) were HBsAg-positive. All 15 pairs of chronic HBV/HDV infection nail and hair samples were β-actin DNA-positive. However, nail HBV DNA was detected in two patients (13%). None of the 15 patients were positive for hair HBV DNA. Nail HDV RNA was detected in three patients (20%). Of the 15 patients, eight (53%) were nail HBsAg-positive. HBsAg and hepatitis delta (HD) antigen were detected in the nails by immunochemical staining. Chimeric mice were not infected with PBS containing HBsAg and HBV DNA elucidated from nails.ConclusionsNails and hair were the reservoir of HBV DNA. Moreover, nails can contain HBsAg, HDV RNA, and HD antigen.

MiRNome profiling of circulating extracellular vesicles in patients with chronic hepatitis delta treated with pegylated interferon alpha

Introduction: MicroRNAs (miRNAs) are short noncoding RNAs involved in the epigenetic regulation of multiple signalling pathways including modulation of viral replication and host immune antiviral response. Specific circulating miRNAs profiles have been associated both with the progression of chronic hepatitis C and with the response to interferon (IFN) treatment in chronic hepatitis B patients. However, data in patients with chronic hepatitis delta virus (HDV) infection are missing.

New actors come into play against hepatitis delta.

Currently chronic hepatitis delta (CHD) represents the most severe form of chronic viral hepatitis. The risk of developing cirrhosis, hepatocellular carcinoma (HCC) and decompensated liver disease is 2-3 times greater in hepatitis delta virus (HDV) infection than in hepatitis B virus (HBV). For instance, in a study carried out in Italy including 299 CHD patients followed for 28 years, 82 (27%) developed cirrhosis, and among these, 46 (56%) developed HCC. The real number of subjects infected by HDV worldwide remains unknown due to the lack of information in many areas, though it has been suggested that the rate of HBsAg carriers co-infected by HDV may be situated between 4.5 and 18%.

Prevalence of Hepatitis D virus antibodies in Hepatitis B patients treated at tertiary care unit at Jabalpur Central India

Hepatitis Delta virus (HDV) infection amongst Hepatitis B virus (HBV) infected patients increases morbidity and mortality. The prevalence varies temporally and spatially. The present study aimed to evaluate the HDV prevalence in central India. Samples received from January 2018 to December 2019 were tested for viral hepatitis markers. Randomly picked 372 HBsAg positive samples were tested for the presence of HDV total antibodies using ELISA, of these 8 were found positive. This study for the first-time documents presence of HDV with 2.1% prevalence from central India. We recommend screening for better patient management and bringing down the disease burden.