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Chronic infection by Hepatitis B Virus (HBV) is one of the most prevalent diseases worldwide. It usually leads to Hepatocellular carcinoma (HCC), chronic liver injury, liver cirrhosis, end-stage liver disease (ESLD) and ultimate death in many cases. New therapeutic agents are being developed for the possible treatment of HBV infection, as almost all the current treatments require the lifelong administration of the drug making the optimization of the therapy essential.

The in-depth knowledge regarding the life cycle of the virus and different genetic mechanisms involving the virus within the body is essential for the development of various therapeutic approaches for the HBV, although it is only partially understood. The HBV is an enveloped virus with its viral genome in the form of partially double-stranded DNA and its entry into the hepatocytes takes place by endocytosis with the help of unknown receptors. It is uncoated after entry into the cytoplasm with the DNA being transported into the nucleus, whereby the relaxed circular partially double-stranded DNA is converted to covalently closed circular DNA (cccDNA), a stable episomal form, that serves as a template for the transcription of 4 viral mRNAs. The pregenomic RNA (pgRNA), which is the largest mRNA is translated in the cytoplasm to form core protein and viral polymerase. The pgRNA is then reverse transcribed to form DNA by the newly formed HBV polymerase, which is the main site of action of most of the oral anti-HBV therapeutics. The DNA is, then incorporated by the core proteins to form capsid within which the viral DNA replication takes place. This DNA then either moves to the nucleus to form more copies or encapsulated for secretion by the three viral surface proteins, which are produced by the translation of the subgenomic RNA. The secreted forms are the progeny virions.

The onset of the HBV infection triggers the host immune response triggering the virus-specific cytotoxic T lymphocytes (CTLs) to produce antiviral cytokines such as interferon and tumor necrosis factors (TNFs) and also in the killing of infected liver cells. Hence, the current therapeutics for the infection focus mainly on

a)the immune modulators including the conventional and the pegylated interferon-α that helps in the enhancement of the host immune defense against the infection. However, the low response rate about 20%-30% of this treatment in the chronic HBV patients as well as the possible development of serious side effects limits its tolerability.

b)The nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) constitute the other method of treatment. It consists of nucleoside or nucleotide analogues that bind to the polymerase and inhibit the reverse transcription of the pgRNA to HBV DNA. However, a major drawback of this treatment is the development of mutations in the polymerase gene of HBV, which have been confirmed by different studies, giving rise to drug resistance.

Introduction of different innovations can help in development of effective therapeutics for the infection. Since, the presence of viral mutations has been confirmed, the genotyping of these mutations before treatment can help in better choice of NRTIs. Moreover, a combination of different NRTIs and introduction of new NRTIs can help in reducing the chance of drug resistance development, thereby decreasing the viral load. Further, the combined therapy of pegylated interferon α with NRTIs can be more effective than the monotherapy on any one by increasing the interferon tolerability and efficacy of the treatment.

The development of different drugs targeting specific points in the life cycle of the HBV has also become possible. The entry inhibitors have been found to reduce the chance of HBV infection especially in case of acute HBV infection or in new liver cells i.e. before liver transplantation when used in combination with NRTIs. The targeting of cccDNA is difficult due to its high stability, however in studies using duck models of HBV, some zinc finger proteins have been found successful in binding to the enhancer region of the duck HBV (DHBV) DNA model and reduced the viral replication. The encapsulation of the viral pregenome and the capsid formation are also found to be potential targets for the development of therapeutics and have helped in the discovery of successful antiviral agents targeting them.

Several studies have been conducted for the development of vaccines against the HBV infection. It has been found that CpG oligodesoxynucleotides (CpG ODN), which are synthetic agonists of Toll like receptor 9, in combination with NRTI Lamivudine (LMV) shows to be a promising combination for the suppression of HBV infection by helping in the innate response. Moreover, a therapeutic vaccine consisting of the immune complexes composed of YIC i.e. yeast derived HBsAg and antibodies has been demonstrated to be successful and safe in phase I and phase IIa trial, whose evaluation is ongoing in phase III trials. Further, a DNA vaccination expressing envelope proteins has been found to be successful in restoring and activation of T cell responses in chronic HBV (CHB) patients by Mancini-Bourgine et al.

Thus, the development of various novel therapeutic agents for HBV infection is ongoing and the clinical outcomes and survival of the CHB patients is possible only with the discovery of potent antiviral agents that can cross the anti-resistance barrier.
Hapatitis B is global health problem.Patients with chronic hepatitis B disease carry significant risk to eventually develop cirrhotic liver disease. Hepatitis B virus (HBV) infection affects ∼350 million people globally and is a leading cause of end-stage liver disease, hepatocellular carcinoma, and mortality.
Above post shared interesting information for this topic.This post provide information on important factor on which current therapeutics are having great focus.
Breakthrough in Hepatitis B Disease!
It has been estimated by WHO that around Six Lac people die every year due to dangerous form of Hepatitis which is known as Hepatitis B. With focus on this deadly disease, researcher at the University of Coimbra had successfully developed oral vaccine for Hepatitis B and is more stable and efficient than injectable vaccine which is available in market.
At the Centre for Neuroscience (CNC), a team of around five scientists had contributed in developing this useful vaccine. Presently these vaccines are test in vivo (that is in animals like mice) and seems to be successful and more promising than injectable vaccine. One more advantage of this is that this does not need only technical staff to administer it. In spite of their effective properties, many vaccines are of no use at the time when it reaches the end user. This is because; they are not stable in high temperature conditions and needs intensive care during cold chain transfer. This is not the case with oral hepatitis B vaccine which has been developed and therefore will be effectively used in many countries which does not have effective cold chain conditions. This will reach to end user with same potential and stability.

The administration of oral vaccine will also have other benefits like may be used for patients already infected with disease. The virus will be fought at the point of administration and thus will also prevent it from being release in bloodstream. This study had taken a decade time but will be effective for thousands of years to come. During the research many nanotechnologist were involved which developed antigens using nanotechnology such that these antigens holds the antigenic properties while not affecting the health by not infecting the host. That is they successfully created antigen with antigenic properties and removing pathogenic properties which exists in Hepatitis B virus.This helped in vaccine development and showed a new way to the field of vaccination .
Thus this research is also aligned with the objectives of the WHO and that is to focus on the development of vaccines which are more stable, effective, cheaper and easier to administer in the body.
Today the number of people are increasing day by day, those who are suffered with the liver diseases. Hepatitis B is dangerous form, it is occurs due to infection by the hepatitis B virus, but medical field is improving and we are having some best clinics and special doctors for any kind of diseases.