Antiviral chemotherapy for the treatment of hepatitis b virus infections (original) (raw)

Hepatitis B virus: old, new and future approaches to antiviral treatment

Journal of Antimicrobial Chemotherapy, 2003

Patients chronically infected with hepatitis B virus (HBV) run the risk of developing cirrhosis and hepatocellular carcinoma in later life. Antiviral treatment offers the only means of preventing such an undesirable outcome. To date, interferon-α (IFN-α), an immunomodulator, and two synthetic nucleoside analogues, lamivudine and adefovir dipivoxil, are the only licensed antiviral agents for the treatment of chronic HBV infection. However, the standard treatment endpoints of loss of HBeAg with or without seroconversion to anti-HBe, normalization of serum transaminase levels, loss of HBV-DNA and improvement in liver histology following monotherapy with either types of agent are only achievable in ∼20-30% of those treated. Long-term treatment with lamivudine is effective in suppressing viral replication, but drug-resistant mutants arise with increased length of treatment. Nevertheless, such mutants appear to be susceptible to adefovir and other nucleoside analogues that are undergoing Phase II/III clinical trials at the moment. Therapeutic vaccination and other molecular approaches such as antisense oligonucleotides, ribozymes, DNA vaccines, dominant-negative proteins and aptamers are possible future antiviral therapies, which will supplement our armamentarium against chronic HBV infection. It seems certain that combination therapies involving two or more nucleoside analogues, immunomodulators or gene therapies will be the future treatment regimens for chronic HBV infection.

Viral Hepatitis B: Established and Emerging Therapies

Current Medicinal Chemistry, 2008

Chronic hepatitis B virus (HBV) infection has a variable course leading to cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis and clinical outcome of HBV infection are strictly dependent on both viral factors, such as life cycle and genotypic variants, and host immune response (i.e. viral persistence). Although therapy of hepatitis B is evolving, which between single and/or combined agents are most effective, how long therapy should last, which criteria should be used to start or continue and switch or stop therapy are to be defined. Two major groups of therapies are currently utilized for chronic hepatitis: immunomodulatory (interferons) and antivirals (nucleoside and nucleotide analogues), all with their own advantages and limitations. In fact, the development of specific antiviral therapies has provoked the appearance of a relevant problem: drug resistances. The emerged antiviral drug-resistant strains of HBV leads to a poor prognosis for infected patients. Thus, many basic and clinical research challenges remain in defining optimal means of management of viral hepatitis B and its related liver diseases. This paper provides a review of new available and developing treatment options for HBV associated liver diseases. In the near future the most realistic therapeutic option for the majority of patients with HBV infection will be combination and/or long-term use of new and stronger antiviral drugs, if they maintain good safety profiles, achieve low resistance rates and will be available at lower prices.

Manuscript Chronic Hepatitis B virus rptfu corrected (2)with references with figures

The role of Utilization of Epigenetics Treatment Strategies Regarding Hepatitis B virus covalently closed circular DNA Silencing with the aim of Attaining Cure:A Narrative Review’’, 2022

World wide vaccination routines have aided in reduction of newer Hepatitis B virus(HBV)Infections. Nevertheless,it has been determined that about 300 million individuals possess Chronic HBV) Infections(CHB) along with possess a greater risk of generation of Hepatocellular carcinoma(HCC). HBV continues to be a robust ,health issue of considerable, significance as well as generation of innovative treatments have assumed an urgent need. Chronic HBV Infections(CHB),is implicated in the continuation of the covalently closed circular DNA(ccc DNA)whose formation in the form of a minichromosome like structures in the nucleus of hepatocytes occurs .In view of the viral transcription taking place intermediately the ccc DNA minichromosome is implicated in the generation of the newer virions along with sustenance of Infection. HBV requires variable host factors for the generation of ccc DNA,besides the that minichromosome is accessible for epigenetic modifications.Two of the HBV proteins namely X(HBx) along with core(HBc) facilitated viral replication by modulation of the ccc DNA epigenome as well as controlling host cell reaction .This is inclusive of viral along with host gene expression , chromatin remodelling , DNA methylation ,anti viral immune reaction,apoptosis,alongwith ubiquitination .Depletion of the ccc DNA minichromosome would aid in a sterilizing recovery, Nevertheless, this might be tough to attain .Thus we decided to carry out a narrative review review utilizing search engine pubmed,google scholar ;web of science ;embase; Cochrane review library utilizing the MeSH terms like CHB; HBx HBc; ccc DNA minichromosome;viral factors;host factors;viral replication;Hepatocellular carcinoma(HCC) ;Epigenetics;DNA methylation;Histone post-translational modifications; DNA methylation; Histone acetylation ; Histonedeacetylasel; zinc finger nucleases; (TALEN); (CRISPR) CRISPR /Cas9; Designer nuclease(s) from 1985 till date .Here we have detailed the ccc DNA epigenome ,the manner in which viral factors along with host factorsimpact transcription besidesrecent advances regarding epigenetic therapies besidesepigenome engineering strategies .

An update on Hepatitis B virus

International Research in Medical and Health Sciences, 2018

Hepatitis B virus (HBV) can cause life-threatening liver infection such as liver cirrhosis and hepatocellular carcinoma. In 1963, Blumberg reported 1st time about the new viral antigen from a blood sample of an Australian aborigine and named as “Australian antigen,” and later this introduced as hepatitis B surface antigen protein of HBV. Approximately 257 million individuals are infected with HBV infection worldwide, and millions of death occurred annually. The virus can spread through sexual contact and parenteral and perinatal routes. HBV causes liver-associated diseases; it can be acute or chronic and symptomatic or asymptomatic disease. The current review provides a detailed account of HBV, its pathogenesis, diagnosis, and treatment.

Hepatitis B virus replication-an update

Journal of Viral Hepatitis, 1996

, the causative agent of type B hepatitis in humans. is the prototypic member of the hepadnaviridae, a family of small enveloped DNA-containing viruses with pronounced host and tissue specificity. This property has greatly hampered progress in understanding the initial events of infection, i.e. attachment, penetration and uncoating. After the discovery, originally made with the duck hepatitis B virus (DHBV), that hepadnaviruses replicate by reverse transcription, DNA transfection of cloned wild-type and mutant HBV genomes into cell lines supporting virion formation has revealed the molecular mecha-nisms of the late steps of the infectious cycle in some detail. During the last few years, such studies have emphasized the differences between hepadnaviral and retroviral replication. Very recent research, however, indicates that the border separating the two viral families may not be as strict as previously thought. In this article, we will briefly summarize the pertinent differences, and will then focus on the new data, with particular emphasis on the initiation of reverse transcription.