Target For Hepatitis Research Articles

Budget impact analysis of two treatment approaches for hepatitis C in Malaysia through the use of voluntary and compulsory licensing options.

A scaled-up treatment cascade with direct-acting antiviral (DAA) therapy is necessary to achieve global WHO targets for hepatitis C virus (HCV) elimination in Malaysia. Recently, limited access to sofosbuvir/daclatasvir (SOF/DAC) is available through compulsory licensing, with access to sofosbuvir/velpatasvir (SOF/VEL) expected through voluntary licensing due to recent agreements. SOF/VEL has superior clinical outcomes but has higher drug acquisition costs compared to SOF/DAC. A stratified treatment cascade might be the most cost-efficient approach for Malaysia whereby all HCV patients are treated with SOF/DAC except for patients with cirrhosis who are treated with SOF/VEL. This study aimed to conduct a 5-year budget impact analysis of the proposed stratified treatment cascade for HCV treatment in Malaysia. A disease progression model that was developed based on model-predicted HCV epidemiology data was used for the analysis, where all HCV patients in scenario A were treated with SOF/DAC for all disease stages while in scenario B, SOF/DAC was used only for non-cirrhotic patients and SOF/VEL was used for the cirrhotic patients. Healthcare costs associated with DAA therapy and disease stage monitoring were included to estimate the downstream cost implications. The stratified treatment cascade with 109 in Scenario B was found to be cost-saving compared to Scenario A. The cumulative savings for the stratified treatment cascade was USD 1.4 million over 5 years. A stratified treatment cascade with SOF/VEL was expected to be cost-saving and can result in a budget impact reduction in overall healthcare expenditure in Malaysia.

Medical Advances in Hepatitis D Therapy: Molecular Targets.

An approximate number of 250 million people worldwide are chronically infected with hepatitis B virus, making them susceptible to a coinfection with hepatitis D virus. The superinfection causes the most severe form of a viral hepatitis and thus drastically worsens the course of the disease. Until recently, the only available therapy consisted of interferon-α, only eligible for a minority of patients. In July 2020, the EMA granted Hepcludex conditional marketing authorization throughout the European Union. This first-in-class entry inhibitor offers the promise to prevent the spread in order to gain control and eventually participate in curing hepatitis B and D. Hepcludex is an example of how understanding the viral lifecycle can give rise to new therapy options. Sodium taurocholate co-transporting polypeptide, the virus receptor and the target of Hepcludex, and other targets of hepatitis D therapy currently researched are reviewed in this work. Farnesyltransferase inhibitors such as Lonafarnib, targeting another essential molecule in the HDV life cycle, represent a promising target for hepatitis D therapy. Farnesyltransferase attaches a farnesyl (isoprenyl) group to proteins carrying a C-terminal Ca1a2X (C: cysteine, a: aliphatic amino acid, X: C-terminal amino acid) motif like the large hepatitis D virus antigen. This modification enables the interaction of the HBV/HDV particle and the virus envelope proteins. Lonafarnib, which prevents this envelopment, has been tested in clinical trials. Targeting the lifecycle of the hepatitis B virus needs to be considered in hepatitis D therapy in order to cure a patient from both coexisting infections. Nucleic acid polymers target the hepatitis B lifecycle in a manner that is not yet understood. Understanding the possible targets of the hepatitis D virus therapy is inevitable for the improvement and development of a sufficient therapy that HDV patients are desperately in need of.

Hepatitis C microelimination among people living with HIV in Taiwan

ABSTRACT To reach the WHO target of hepatitis C virus (HCV) elimination by 2025, Taiwan started to implement free-of-charge direct-acting antiviral (DAA) treatment programme in 2017. Evaluating the progress of HCV microelimination among people living with HIV (PLWH) is a critical step to identify the barriers to HCV elimination. PLWH seeking care at a major hospital designated for HIV care in Taiwan between January 2011 and December 2021 were retrospectively included. For PLWH with HCV-seropositive or HCV seroconversion during the study period, serial HCV RNA testing was performed using archived samples to confirm the presence of HCV viremia and estimate the prevalence and incidence of HCV viremia. Overall, 4199 PLWH contributed to a total of 27,258.75 person-years of follow-up (PYFU). With the reimbursement of DAAs and improvement of access to treatments, the prevalence of HCV viremia has declined from its peak of 6.21% (95% CI, 5.39–7.12%) in 2018 to 2.09% (95% CI, 1.60–2.77%) in 2021 (decline by 66.4% [95% CI, 55.4–74.7%]); the incidence has declined from 25.94 per 1000 PYFU (95% CI, 20.44–32.47) in 2019 to 12.15% per 1000 PYFU (95% CI, 8.14–17.44) (decline by 53.2% [95% CI, 27.3–70.6%]). However, the proportion of HCV reinfections continued to increase and accounted for 82.8% of incident HCV infections in 2021. We observed significant declines of HCV viremia among PLWH with the expansion of the DAA treatment programme in Taiwan. Further improvement of the access to DAA retreatments is warranted to achieve the goal of HCV microelimination.

Implications of Birth-Dose Vaccination against Hepatitis B Virus in Southeast Asia.

The World Health Organization (WHO) South-East Asia Regional Office (SEARO) covers 11 countries with a combined population of about 2 billion people, making it the most populous of the six WHO regions. In 1992, the WHO advocated including the hepatitis B vaccine in the Expanded Program of Immunization (EPI) and vaccinating all infants and children three times within 1 year of birth (HepB3). Recently, the WHO advocate birth-dose hepatitis B vaccination (HepB-BD) as soon as possible after birth, preferably within 24 hours. In 2016, the SEARO endorsed a regional hepatitis B control goal with a target of hepatitis B surface antigen (HBsAg) seroprevalence of ≤1% among children aged ≥5 years by 2020. Of the 11 SEARO countries, four achieved this target on schedule. Out of these four countries, two countries (Bangladesh and Nepal) have not adopted HepB-BD in EPI program. On the other hand, the coverage of HepB3 is not satisfactory in some SEARO countries, including India which adopted HepB-BD but could not achieve the overall target of SEARO. Thus, it is a point of debate whether emphasis should be placed on proper implementation of HepB3 or whether a new agenda of HepB-BD should be incorporated in developing countries of SEARO. The article discusses strengthening and expanding the Hepatitis B vaccination program in SEARO countries with an emphasis on HepB and HepB-BD programs.

Hepatitis C virus elimination: laying the foundation for achieving 2030 targets.

The World Health Organization’s targets for hepatitis C elimination by 2030 are ambitious, but, in 2020, global leadership demonstrated by Egypt, innovative strategies to improve linkage to treatment for marginalized populations and the broadened capacity of direct-acting antiviral therapy have been promising for enhanced global elimination efforts.

Development of an in vivo delivery system for CRISPR/Cas9-mediated targeting of hepatitis B virus cccDNA

Chronic hepatitis B virus (HBV) infection constitutes a global health issue with limited current therapeutic efficacy owing to the persistence of viral episomal DNA (cccDNA). The CRISPR/Cas9 system, a newly developed, powerful tool for genome editing and potential gene therapy, requires efficient delivery of CRISPR components for successful therapeutic application. Here, we investigated the effects of lentiviral- or adeno-associated virus 2 (AAV2) vector-mediated delivery of 3 guide (g)RNAs/Cas9 selected from 16 gRNAs. These significantly suppressed HBV replication in cells, with WJ11/Cas9 exhibiting highest efficacy and chosen for in vivo study. AAV2/WJ11-Cas9 also significantly inhibited HBV replication and significantly reduced cccDNA in the tested cells. Moreover, AAV2/WJ11-Cas9 enhanced entecavir effects when used in combination, indicative of different modes of action. Notably, in humanized chimeric mice, AAV2/WJ11-Cas9 significantly suppressed HBcAg, HBsAg, and HBV DNA along with cccDNA in the liver tissues without significant cytotoxicity; accordingly, next generation sequencing data showed no significant genomic mutations. To our knowledge, this represents the first evaluation of the CRISPR/Cas9 system using an HBV natural infection mode. Therefore, WJ11/Cas9 delivered by comparatively safer AAV2 vectors may provide a new therapeutic strategy for eliminating HBV infection and serve as an effective platform for curing chronic HBV infection.

Use of Andrographis paniculata (Burm. f.) Nees for Treating Hepatitis

Andrographis paniculata (Burm. f.) Nees (APN) is a medicinal plant widely used in Asian countries. APN is used for its anti-inflammatory and antiviral properties. Previous studies did not clarify its pathway to treat hepatitis under the next generation of natural antibiotics. No definite trend has found expression in the multi-component Chinese medicine (MCCM). Besides, the research and development of a particular component in APN can not cover the most pharmacological effects of APN treating hepatitis. Based on the current information biology data, this review found that the intersection number of APN and hepatitis were 1,016 from 3,922 APN PPI targets and 1,818 hepatitis targets, respectively, according to current data. The filtered prediction outcome suggests that the MCCM of APN treating hepatitis were wogonin, oroxylin A, and andrographolide, which accounted for more than 95% of the compound contribution index of APN treating hepatitis. The predicated primary related pathways were the Notch, thyroid hormone, hepatitis B, and prolactin signalling pathways. This review serves to summarize the current research on APN to indicate a specific research direction to determine the pharmacological mechanism of APN and the interaction between drug targets and disease targets, laying a foundation for the subsequent development of its MCCM, new drugs, and auxiliary drugs.

A bioinformatics investigation into molecular mechanism of Yinzhihuang granules for treating hepatitis B by network pharmacology and molecular docking verification

Yinzhihuang granules (YZHG) is a patented Chinese medicine for the treatment of hepatitis B. This study aimed to investigate the intrinsic mechanisms of YZHG in the treatment of hepatitis B and to provide new evidence and insights for its clinical application. The chemical compounds of YZHG were searched in the CNKI and PUBMED databases, and their putative targets were then predicted through a search of the SuperPred and Swiss Target Prediction databases. In addition, the targets of hepatitis B were obtained from TTD, PharmGKB and DisGeNET. The abovementioned data were visualized using Cytoscape 3.7.1, and network construction identified a total of 13 potential targets of YZHG in the treatment of hepatitis B. Molecular docking verification showed that CDK6, CDK2, TP53 and BRCA1 might be strongly correlated with hepatitis B treatment. Furthermore, GO and KEGG analyses indicated that the treatment of hepatitis B by YZHG might be related to positive regulation of transcription, positive regulation of gene expression, the hepatitis B pathway and the viral carcinogenesis pathway. Network pharmacology intuitively shows the multicomponent, multitarget and multichannel pharmacological effects of YZHG in the treatment of hepatitis B and provides a scientific basis for its mechanism of action.

Hepatitis C Virus Infection: A Brief Review

Hepatitis C, caused by hepatitis C virus (HCV) was originally described as parenterally transmitted non-A non-B hepatitis. Since its discovery in 1989, the field of HCV research has become a shining example of successful translation of basic research wherein in a short of span of just 30 years the virus was discovered, highly sensitive and specific diagnostic assays were developed, epidemiology and clinical characteristics of the disease were well defined and now with the availability of highly efficacious antiviral therapies many countries are already on their way to achieving World Health Organization’s (WHO) elimination targets of hepatitis C by 2030. However, much work needs to be done to eliminate hepatitis C especially in resource poor countries. Most recent data show an estimated 71 million people are currently infected with HCV worldwide and approximately 400,000 people die each year from causes related to HCV. Of these estimates, more than 13 million HCV infected persons are in India and Pakistan (Figure 1). Despite the availability of a cure for hepatitis C, only 20% of those infected patients have been diagnosed (1). In order to achieve the WHO targets of hepatitis C elimination, concerted efforts will have to made to make affordable and reliable diagnostics available worldwide.

A micro-elimination approach to addressing hepatitis C in Turkey

BackgroundIn 2016, WHO passed the Global Health Sector Strategy on Viral Hepatitis (GHSS), calling for its elimination by 2030. Two years later, Turkey approved a strategy to reach the WHO targets. This study reports new national prevalence data, breaks it down by subpopulation, and models scenarios to reach HCV elimination.MethodsLiterature was reviewed for estimates of HCV disease burden in Turkey. They were discussed with stakeholders and used as inputs to develop a disease burden model. The infected population was estimated by sequelae for the years 2015–2030. Three scenarios were developed to evaluate the disease burden in Turkey: a Base 2017 scenario, representing the current standard of care in Turkey; an increased treatment scenario, representing the impact of improved access to DAAs; and a WHO targets scenario, which meet the WHO GHSS viral hepatitis targets of a 65% reduction in mortality and 90% diagnosis rate of the infected population by 2030.ResultsAt the beginning of 2017, 271,000 viremic infections were estimated. Of these, 58,400 were diagnosed and 10,200 treated. Modelling results showed that, with the current treatment paradigm in Turkey, by 2030 the total number of viremic HCV infections would decline by 35%, while liver-related deaths, hepatocellular carcinoma (HCC), and decompensated cirrhosis would decrease by 10–25%. In the increased treatment scenario, by 2030 viremic HCV infections would decrease by 50%; liver-related deaths, HCC and decompensated cirrhosis would decrease by 45–70%. In the WHO targets scenario, HCV infections would decrease by 80%; sequelae would decrease by 80–85%. Data on disease burden in micro-elimination target subpopulations are largely unavailable.ConclusionsTo meet the WHO Global Health Sector Strategy targets for the elimination of HCV, Turkey needs to increase treatment. Better data are needed as well as countrywide access to DAAs.

Community-Based Strategies to Improve Screening, Diagnosis and Linkage to Care for Patients with Chronic Hepatitis B

Chronic hepatitis B (CHB) places 3.5% of the world population at risk of dying from liver failure or liver cancer. Effective antiviral therapies can change disease outcomes, provided that CHB screening and linkage to care can be delivered at population level, to reach the vast numbers of undiagnosed people. We therefore reviewed the experience of community-based CHB screening programs reported in the English literature since 2014. Twenty papers met eligibility criteria and only one originated from a low-income country. The two randomised studies found that culturally tailored hepatitis education increased hepatitis testing. Successful linkage to care was facilitated by partnerships with community-based organisations and the use of bilingual patient navigators. Point of care testing and chain referral sampling were successfully tested in two programs. These studies demonstrated that community-based interventions can screen large numbers of people and could deliver the population-level outcomes required to meet the WHO targets of hepatitis B elimination.

Establishment and development of national community-based collaborative innovation demonstration areas to achieve the control target of hepatitis B in China

BackgroundThe major infectious diseases of hepatitis B has constituted an acute public health challenge in China. An effective and affordable HBV control model is urgently needed. A national project of Community-based Collaborative Innovation HBV (CCI-HBV) demonstration areas has optimized the existing community healthcare resources and obtained initial results in HBV control.MethodsBased on the existing community healthcare network, CCI-HBV project combined the community health management and health contract signing service for long-staying residents in hepatitis B screening. Moreover, HBV field research strategy was popularized in CCI-HBV areas. After screening, patients with seropositive results were enrolled in corresponding cohorts and received treatment at an early stage. And the uninfected people received medical supports including health education through new media, behavior intervention and HBV vaccinations. In this process, a cloud-based National Information Platform (NIP) was established to collect and store residents’ epidemiological data. In addition, a special quality control team was set up for CCI project.ResultsAfter two rounds of screening, HBsAg positive rate dropped from 5.05% (with 5,173,003 people screened) to 4.57% (with 3,819,675 people screened), while the rate of new HBV infections was 0.28 per 100 person-years in the fixed cohorts of 2,584,322 people. The quality control team completed PPS sampling simultaneously and established the serum sample database with 2,800,000 serum samples for unified testing.ConclusionsCCI-HBV project has established a large-scale field research to conduct whole-population screening and intervention. We analyzed the HBsAg prevalence and new infection rate of HBV in the fixed population for the epidemic trend and intervention effect. The purpose of CCI-HBV project is to establish and evaluate a practical model of grid management and field strategy, to realize the new goal to control hepatitis B in China. To provide policymakers with a feasible model, our results are directly applicable.Trial registrationThe project was funded by the Major Projects of Science Research for the 11th and 12th five-year plans of China, entitled “The prevention and control of AIDS, viral hepatitis and other major infectious diseases”, Grant Nos. 2009ZX10004901, 2011ZX10004901, 2013ZX10004904, 2014ZX10004007 and 2014ZX10004008.

How can we achieve WHO's elimination target for hepatitis C incidence?

How can we achieve WHO's elimination target for hepatitis C incidence?

Achieving World Health Organization targets for hepatitis B by 2030: Results from 17 WHO AFRO Countries

Achieving World Health Organization targets for hepatitis B by 2030: Results from 17 WHO AFRO Countries

Therapeutic targets for hepatitis D virus infection

Therapeutic targets for hepatitis D virus infection

Novel targets for hepatitis B virus therapy.

Treatment with either pegylated interferon-alpha (pegIFN-α) or last generation nucleos(t)ide analogues (NAs) successfully leads to serum viral load suppression in most chronically infected hepatitis B (CHB) patients, but HBsAg loss is only achieved in 10% of the cases after a 5-year follow-up. Thus, therapy must be administered long-term and it will not completely eliminate infection because of the persistent hepatitis B virus (HBV) minichromosome in infected cells, and cannot completely abolish the risk of developing severe sequelae such as cirrhosis and hepatocellular carcinoma. Recent progress in the development of in vitro and in vivo models of HBV infection have helped renew interest in the investigation of the viral life cycle, as well as specific virus-host cell interactions to identify new targets for the development of new antiviral drugs. This includes either direct inhibition of viral replication by targeting fundamental steps such as entry, cccDNA formation/stability, viral transcripts, capsid assembly and secretion or the manipulation of the host immune system for better defence against infection. Multiple strategies are currently under investigation, including boosting endogenous innate responses and/or restoring adaptive immunity via engineering of HBV-specific T cells or via the use of inhibitors of negative regulators, as well as therapeutic vaccines. It is increasingly clear that multiple therapeutic strategies must be combined to reach a cure of HBV and that the definition of clinical, virological and immunological correlates for the management of treatment are urgently needed.

Identification of host cell requirements and antivrial targets for hepatitis D virus infection

Identification of host cell requirements and antivrial targets for hepatitis D virus infection

FAKTOR˗FAKTOR YANG BERHUBUNGAN DENGAN PEMBERIAN IMUNISASI HEPATITIS B˗0 PADA IBU YANG MEMILIKI BAYI DI PUSKESMAS BONAI DARUSSALAM PASIR PANGARAIAN KABUPATEN ROKAN HULU

Universal Child Immunization (UCI) target of Hepatitis B immunization must be achieved 80 % in national, province, regency or even a village. PD3I surveillance data shows scope of HB˗0 (0˗7 days) immunization in Riau, from 2007-2013 still below national targets. Based on information from paramedic in Bonai Darussalam Health Care, low immunization coverage because some people do not know the benefits and afraid if their infants get immunization an earlier time. This study aims to understand related factors of provision Hepatitis B–0 immunization in Bonai Darussalam Health Care, Pasir Pangaraian, Rokan Hulu in 2016. Quantitative research methods and research design used cross sectional. The study was conducted in Bonai Darussalam Health Care, Pasir Pengaraian in February 2016 using questionnaires with 50 people total respondents. Sampling was taken by accidental sampling technique. The results show that 42 people (84%) did not give HB- 0 immunization. Test results chi-square statistic show connection between respondent’s knowledge with HB-0 immunization OR = 2.0 (95% CI 1.22 to 3.26), futhermore, there is a correlation relationship between the respondent’s attitudes with immunization HB-0 OR = 21.8 (95% CI 1.19 to 2.72), and the relationship between the respondent's educational with HB-0 immunization OR = 1.8 (95% CI 1.20 to 2.95). A recommendation for paramedic in Bonai Darussalam Health Care is to improve their performance in terms of providing information to mothers who have babies, private midwives and herbalists in the area and it hopes that mother could be motivated to provide immunization HB-0.

In Silico Approaches to the Design of NS5A Inhibitors.

In recent years, nonstructural protein 5A (NS5A) has rapidly emerged as a promising therapeutic target for Hepatitis C (HCV) virus therapy. It is involved in both viral RNA replication and virus assembly and NS5A plays a critical role in the regulation of HCV life cycle. NS5A replication complex inhibitors (NS5A RCIs) have demonstrated strong antiviral activity in vitro and in vivo. However, wild-type resistance mutations and a wide range of genotypes significantly reduce their clinical efficacy. The exact mechanism of NS5A action still remains elusive, therefore several in silico models have been constructed to gain insight into the drug binding and subsequent structural optimization to overcome resistance. This paper provides a comprehensive overview of the computational studies towards NS5A mechanism of action and the design of novel small-molecule inhibitors.

Base pairing between hepatitis C virus RNA and 18S rRNA is required for IRES-dependent translation initiation in vivo.

Degeneracy in eukaryotic translation initiation is evident in the initiation strategies of various viruses. Hepatitis C virus (HCV) provides an exceptional example--translation of the HCV RNA is facilitated by an internal ribosome entry site (IRES) that can autonomously bind a 40S ribosomal subunit and accurately position it at the initiation codon. This binding involves both ribosomal protein and 18S ribosomal RNA (rRNA) interactions. In this study, we evaluate the functional significance of the rRNA interaction and show that HCV IRES activity requires a 3-nt Watson-Crick base-pairing interaction between the apical loop of subdomain IIId in the IRES and helix 26 in 18S rRNA. Mutations of these nucleotides in either RNA dramatically disrupted IRES activity. The activities of the mutated HCV IRESs could be restored by compensatory mutations in the 18S rRNA. The effects of the 18S rRNA mutations appeared to be specific inasmuch as ribosomes containing these mutations did not support translation mediated by the wild-type HCV IRES, but did not block translation mediated by the cap structure or other viral IRESs. The present study provides, to our knowledge, the first functional demonstration of mRNA-rRNA base pairing in mammalian cells. By contrast with other rRNA-binding sites in mRNAs that can enhance translation as independent elements, e.g., the Shine-Dalgarno sequence in prokaryotes, the rRNA-binding site in the HCV IRES functions as an essential component of a more complex interaction.