Background: It is assumed that the prevalence of hepatitis D in HBsAg-positive individuals reaches 4.5-13% in the world, and on average about 3% in Europe. Data from several European countries, including Slovakia, are missing or are from an older period. Methods: We analyzed all available data on hepatitis D from Slovakia, including reports from the Slovak Public Health Authority and the results of one prospective study, and three smaller surveys. The determination of anti-HDV IgG and IgM antibodies and/or HDV RNA was used to detect hepatitis D. Results: In the years 2005-2022, no confirmed case of acute or chronic HDV infection was reported in Slovakia. The presented survey includes a total of 343 patients, of which 126 were asymptomatic HBsAg carriers, 33 acute hepatitis B, and 184 chronic hepatitis B cases. In a recent prospective study of 206 HBsAg-positive patients who were completely serologically and virologically examined for hepatitis B and D, only 1 anti-HDV IgG positive and no anti-HDV IgM or HDV RNA positive cases were detected. In other smaller surveys, 2 anti-HDV IgG positive patients were found without the possibility of HDV RNA confirmation. In total, only 3 of 329 HBsAg-positive patients (0.91%) tested positive for anti-HDV IgG antibodies and none of 220 tested positive for HDV RNA. Conclusion: The available data show that Slovakia is one of the countries with a very low prevalence of HDV infection reaching less than 1% in HBsAg-positive patients. Routine testing for hepatitis D is lacking in Slovakia, and therefore it is necessary to implement testing of all HBsAg-positive individuals according to international recommendations.

Hepatitis delta virus (HDV) infection causes the most severe form of viral hepatitis but little is known about the molecular mechanisms involved. The recently developed HDV mouse model based on the delivery of HDV replication-competent genomes using adeno-associated vectors (AAV) develop a liver pathology very similar to the human disease, and allowed us to perform mechanistic studies. We have generated different AAV-HDV mutants to eliminate the expression HDV antigens (HDAgs), characterized them both in vitro and in vivo. We confirmed that S-HDAg is essential for HDV replication and cannot be replaced by L-HDAg or host cellular proteins, and the L-HDAg is essential for HDV infectious particle production. We have also found that the lack of L-HDAg resulted in the increase of of S-HDAg expression levels and the exacerbation of liver damage which is T cell independent but is associated with an increment in liver inflammation. Interestingly, early expression of L-HDAg significantly ameliorated the liver damage induced by the mutant expressing only the S-HDAg. In summary, the use of AAV-HDV represents a very attractive platform to interrogate in vivo the role of viral components in the HDV life cycle and to better understand the mechanism of HDV-induced liver pathology.

Coinfection of B virus (HBV) and hepatitis Delta virus (HDV) lead to severe forms of progressive liver diseases. However, commercially available antiviral drugs have shown considerable adverse effects and low efficacy in managing these patients. Thus, there is a pressing need to develop new, innovative, and evidence-based therapies for these pathological entities. In line with this, some investigators have attempted to develop anti-viral drugs targeting HBV/HDV coinfection. In another development, investigators have also attempted to establish immune therapy targeting for HBV infection as recovery or effective control of HBV infection also lead to efficient control of HDV infection. This review has discussed an account of the evolving antiviral and immune therapeutic drugs for HBV/HDV infection. Also, based on current scientific knowledge how we have described the pros and cons of these drugs as no suitable drug has been developed during the last forty years for treating HBV infection except the availability of two” repurposed drugs”; interferons and its derivatives and nucleoside analogs, for managing HBV or HBV/HDV coinfection. It seems that an evolving and innovative therapeutic regimen that combines both antiviral drugs and immune modulators may be the best and realistic option for management of HBV/HDV coinfection.

Hepatitis D virus (HDV) infection represents the most severe form of chronic viral hepatitis. We have shown that the delivery of HDV replication-competent genomes to the hepatocytes using adenoassociated virus (AAV-HDV) as gene delivery vehicles offers a unique platform to investi-gate the molecular aspects of HDV and associated liver damage. Here, we generated HDV ge-nomes modified by site directed mutagenesis aimed to: i) prevent some post-translational modi-fications of HDV antigens (HDAgs) such as Large-HDAg (L-HDAg) isoprenylation or Short-HDAg (S-HDAg) phosphorylation ii) alter the localization of HDAgs within the subcellular compartments and iii) inhibit the right conformation of the delta ribozyme. First, the different HDV mutants were tested in vitro using plasmid-transfected Huh-7 cells and then in vivo in C57BL/6 mice using AAV vectors. We found that Ser 177 phosphorylation and the ribozymal ac-tivity are essential for HDV replication and HDAg expression. Mutation of the isoprenylation domain prevent the formation of infectious particles and increase cellular toxicity and liver dam-age. Finally, altering the intracellular localization od HDAg have a profound on viral replication in vivo but liver toxicity is maintained. Mutation in the nuclear export signal impair the for-mation of infectious viral particles. These findings contribute valuable insights into the intricate mechanisms of HDV biology and have implications for therapeutic considerations