Evaluating the Efficacy of Repurposed Antiretrovirals in Hepatitis B Virus Treatment: A Narrative Review of the Pros and Cons

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 925 - 925

Опубликована: Янв. 23, 2025

Human immunodeficiency virus (HIV) and hepatitis B (HBV) continue to be global public health issues. Globally, about 39.9 million persons live with HIV in 2023, according the Joint United Nations Programme on HIV/AIDS (UNAIDS) 2024 Fact Sheet. Consequently, World Health Organisation (WHO) reported that 1.5 new cases of HBV occur, approximately 820 thousand mortalities yearly. Conversely, lower percentage (30%) receive a diagnosis is setback achieving WHO 2030 target for zero globally. This has necessitated concern repurpose antiretroviral (ARV) drugs treatment diseases. review provides an introductory background, including pros cons repurposing antiretrovirals (ARVs) treatment. We examine similarities replication mechanisms between HBV. further investigate some clinical studies trials co-infected mono-infected patients HIV–HBV. The topical keywords ARV drugs, therapy, Hepatitis title, abstracts are searched PubMed, Web Science, Google Scholar. advanced search includes period 2014–2024, full text, trials, randomized control review. results filtered from 361 51 relevant articles. investigations revealed replicate via common route known as ‘reverse transcription’. Clinical trial indicate early initiation ARVs, particularly tenofovir disoproxil fumarate (TDF) part regimen, significantly reduced viral load patients. In HBV, timely correct precise medication essential reduction. Therefore, genetic profiling pivotal successful drug Pharmacogenetics enables prediction right dosages, specific individual responses, reactions. study uniquely explores intersection pharmacogenetics optimized therapy. Additional vivo, silico research important validation potency, optimum dosage, safety repurposed Furthermore, prioritization collaborations comprising regulators funders foster clinically adopting incorporating ARVs therapy recommended.

Язык: Английский

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Chronic Hepatitis B Virus Persistence: Mechanisms and Insights

Cureus, Год журнала: 2025, Номер unknown

Опубликована: Фев. 13, 2025

Chronic hepatitis B (CHB) virus infection can lead to severe liver diseases, including cirrhosis and hepatocellular carcinoma. The chronicity of the (HBV) occurs because persistence viral covalently closed circular DNA (cccDNA) within hepatocytes. cccDNA serves as template for replication is central HBV, maintaining a reservoir host. Despite therapeutic advancements, eliminating remains elusive due its evasion immune surveillance. This review explores formation maintenance cccDNA, highlighting host factors influencing stability replication. It also discusses current treatment strategies, interferon-based therapies nucleoside/nucleotide analogs, which aim suppress Emerging such gene editing molecular interventions hold promise targeting directly. Currently, research focused on making medications that target interest disrupt or clear reservoir. However, future should focus innovative approaches directly minichromosome, aiming sustained suppression potentially cure HBV infection.

Язык: Английский

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Chronic Hepatitis B Infection: New Approaches towards Cure

Biomolecules, Год журнала: 2023, Номер 13(8), С. 1208 - 1208

Опубликована: Авг. 1, 2023

Chronic hepatitis B virus (HBV) infection leads to the development of cirrhosis and hepatocellular carcinoma. Lifelong treatment with nucleotides/nucleoside antiviral agents is effective at suppressing HBV replication, however, adherence daily therapy can be challenging. This review discusses recent advances in long-acting formulations for prevention, which could potentially improve adherence. Promising new compounds that target distinct steps life cycle are summarized. In addition treatments suppress viral curative strategies focused on elimination covalently closed circular DNA inactivation integrated from infected hepatocytes. We highlight promising antivirals genome editing or deactivation persistent products development.

Язык: Английский

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Prospects for Controlling Hepatitis B Globally

Pathogens, Год журнала: 2024, Номер 13(4), С. 291 - 291

Опубликована: Март 29, 2024

Infection with the hepatitis B virus (HBV) is highly prevalent globally. Over 250 million people suffer from chronic B, and more than 800,000 patients die each year due to complications, including liver cancer. Although protective HBV vaccines are recommended for all newborns, global coverage suboptimal. In adults, sexual transmission by far most frequent route of contagion. The WHO estimates that 1.5 new infections occur annually. Oral nucleos(t)ide analogues entecavir tenofovir antivirals prescribed as therapy. Almost adherent medication achieve undetectable plasma viremia beyond 6 months monotherapy. However, less 5% anti-HBs seroconversion, viral rebound occurs following drug discontinuation. Therefore, need be lifelong. New long-acting formulations being developed will maximize treatment benefit overcome adherence barriers. Furthermore, antiviral agents in development, entry inhibitors, capside assembly modulators, RNA interference molecules. use combination therapy pursues a functional cure, meaning it negative both circulating HBV-DNA HBsAg. Even when this goal achieved, cccDNA reservoir within infected hepatocytes remains signal past infection, can reactivate under immune suppression. gene therapies, editing, eagerly pursued silence or definitively disrupt genomes and, way, ultimately cure B. At time, three actions taken push eradication globally: (1) expand universal newborn vaccination; (2) perform once-in-life testing adults identify susceptible persons could vaccinated (or re-vaccinated) unveil asymptomatic carriers treatment; (3) provide earlier carriers, aviremic reduces risk clinical progression transmission.

Язык: Английский

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Identification of novel antiviral host factors by functional gene expression analysis using in vitro HBV infection assay systems

PLoS ONE, Год журнала: 2025, Номер 20(3), С. e0314581 - e0314581

Опубликована: Март 6, 2025

To cure hepatitis B virus (HBV) infection, it is essential to elucidate the function of hepatocyte host factors in regulating viral life cycle. Signaling and transcription activator (STAT)1 play important roles immune responses, but STAT1-independent pathways have also been shown biological reactivity. Using an vitro HBV infection assay system, current study aimed investigate that contribute control by comprehensive functional screening. The system was established using primary human hepatocytes (PXB cells) infected with derived from a plasmid containing 1.3-mer genome. Comprehensive studies were performed small interfering RNA (siRNA) vector transfection analyzed microarrays. Knockdown STAT1 increased products HBV-transfected HepG2 cells, decreased HBV-infected PXB cells. microarray cells knockdown. Fumarylacetoacetate hydrolase (FAH) extracted siRNA genes altered Transfection FAH inhibited replication. Dimethyl fumarate (DMF), methyl ester metabolite, showed antiviral effects inducing autophagy anti-HBV-related genes. Independently STAT1, identified as factor contributes its DMF, exhibited activity. These results suggest novel metabolites may be innovative therapeutic strategy

Язык: Английский

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Inhibition of Hepatitis B Virus Replication by a Novel GalNAc–siRNA In Vivo and In Vitro

ACS Omega, Год журнала: 2025, Номер 10(1), С. 484 - 497

Опубликована: Янв. 3, 2025

Current antiviral therapy for the chronic hepatitis B virus (HBV) has a low clinical cure rate, high administration frequency, and limited efficacy in reducing HBsAg levels, leading to poor patient compliance. Novel agents are required achieve HBV functional cure, reduction of antigenemia may enhance activation effective long-lasting host immune control. HT-101 is siRNA currently phase I trials with promising prospects future applications. By designing synthesizing targeting conserved S region, we evaluated its inhibitory effect on biomarkers across four different genotypes (A–D). Additionally, potential cytotoxic effects were investigated. The vivo duration inhibition assessed using HBV/adeno-associated mouse model. EC50 values DNA, HBsAg, HBeAg, RNA supernatant HepG2.2.15 cells determined be 0.3348 0.1696, 4.329, 2.831 nM, respectively, while CC50 against viability Hep2, H1 HeLa, MRC-5, HEK293, Huh7 cell lines all exceeded 1 μM significantly. Compared vehicle group from days 7 70 postdosing, especially high-dose (9 mpk), plasma levels DNA significantly reduced mean ranging 1.72 3.38 log10 copy/mL due suppression below lower limit quantitation (LLOQ), ultimately induction anti-HBs. In summary, preclinical data demonstrate that represents significant breakthrough antigens provides strategy HBV.

Язык: Английский

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Potential Benefits of In Silico Methods: A Promising Alternative in Natural Compound’s Drug Discovery and Repurposing for HBV Therapy

Pharmaceuticals, Год журнала: 2025, Номер 18(3), С. 419 - 419

Опубликована: Март 16, 2025

Hepatitis B virus (HBV) is an important global public health issue. The World Health Organization (WHO) 2024 Global Report estimated that the prevalence of people living with HBV infection 254 million, incidence 1.2 million new infections yearly. Previous studies have shown natural compounds antiviral inhibition potentials. In silico methods such as molecular docking, virtual screening, pharmacophore modeling, quantitative structure–activity relationship (QSAR), and dynamic simulations been successfully applied in identifying bioactive strong binding energies treatment targets. COVID-19 pandemic necessitated importance repurposing already approved drugs using methods. This study aimed at unveiling benefits techniques a potential alternative compounds’ drug discovery for therapy. Relevant articles from PubMed, Google Scholar, Web Science were retrieved analyzed. Furthermore, this comprehensively reviewed literature containing identified essential proteins. Notably, hesperidin, quercetin, kaempferol, myricetin, flavonoids hepatitis surface antigen (HBsAg). investigation reveals offer understanding mechanisms action, reveal previously overlooked viral targets (including PreS1 Domain HBsAg cccDNA (Covalently Closed Circular DNA) regulators, facilitate creation specific inhibitors. integration silico, vitro, vivo insights further highlight Moreover, combination compounds, approach, improves chances personalized precision medicine treatment. Therefore, we recommend strategies combine vivo, approaches to effective drugs.

Язык: Английский

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An Investigative Study of LGALSL and HLA‐DRB1 as Prognostic Biomarkers and Therapeutic Targets in Chronic Hepatitis B Patients With Persistent HBV DNA Viremia Under Entecavir Treatment

Journal of Medical Virology, Год журнала: 2025, Номер 97(4)

Опубликована: Апрель 1, 2025

Despite significant advances in chronic hepatitis B (CHB) treatment, some patients receiving entecavir (ETV) still experience poor clinical outcomes. Identifying host factors contributing to ETV anti-HBV failure CHB with persistent HBV DNA positivity is crucial for developing targeted therapies. We conducted a comprehensive study using univariate and reverse Mendelian randomization (MR), incorporating sequencing data publicly available genetic data, followed by gene set variation analysis (GSVA), enrichment (GSEA) immune cell infiltration systematically explore causal associations between CHB. Univariate MR analyses revealed inverse association increased HLA-DRB1 levels risk (odds ratio [OR] 0.607, 95% confidence interval [CI] 0.478-0.771, p = 0.00004), while LGALSL were significantly associated heightened of prognosis (OR 1.110, CI: 1.017-1.212, 0.01885), as estimated the variance weighting (IVW) method. Analysis showed higher HLA mast group. positive correlation HLA, whereas negative correlation. Compared favorable prognoses, those prognoses exhibited serum (ELISA), lower expression peripheral blood mononuclear cells (PBMCs) (qPCR), liver tissue (IHC). Therefore, may serve potential prognostic biomarkers ETV, providing novel avenues diagnosis treatment.

Язык: Английский

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Spatial and temporal distribution patterns and factors influencing hepatitis B in China: a geo-epidemiological study

BMC Public Health, Год журнала: 2025, Номер 25(1)

Опубликована: Апрель 4, 2025

China is a country with an extremely high disease burden of hepatitis B. Spatiotemporal analysis B from socioeconomic perspective great significance for reducing the burden, but there still relative lack research. The age-period-cohort model and spatial distribution maps describe three-dimensional characteristics Spatial autocorrelation spatiotemporal scanning were used to analyze characteristics. random forest algorithm was screen potential influencing factors. geographic detector interaction patterns variables. Finally, geographically temporally weighted regression established effects variables on incidence rate at different scales. From 2004 2023, total 20,376,898 cases reported in China. decreased 3.31% per year, vaccination has led this downward trend, accompanied by significant birth cohort effect. And it shows aggregated characteristic, which highlights inequality geographical distribution. Stronger explanations found number people end each year (q = 0.1949; where q value refers explanatory ability independent variable dependent variable) proportion rural population 0.1895), even stronger explanation 0.5366). magnitude direction effect factors also varied regions, factor not event. later are born, lower northwest southwest regions main hotspots, tendency spread southern beds medical institutions should be increased densely populated areas, economic development accelerated sparsely areas. Hepatitis prevention control prioritized coupled enhanced awareness campaigns areas catch-up programs targeting high-risk populations.

Язык: Английский

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Impacts of PEG-IFN-α-2b Combination Therapy on Liver Function, Immune Factors and Risk Factors in Patients With HBV Infection: A Retrospective Study

British Journal of Hospital Medicine, Год журнала: 2025, Номер unknown, С. 1 - 16

Опубликована: Апрель 15, 2025

Aims/Background Hepatitis B virus (HBV) infection poses a challenge to global healthcare. Peginterferon alfa-2b (PEG-IFNα-2b) is an effective treatment for HBV infection. This study aimed explore the efficacy of PEG-IFNα-2b combined with entecavir in infection, its effect on liver function and immune factors, risk factors affecting prognosis patients Methods The clinical data 184 who were treated at Jinhua Central Hospital from January 2021 2024 collected retrospective analysis. Patients divided into control group (not receiving antiviral treatment, n = 34), standard (receiving entecavir, 85), combination (PEG-IFNα-2b 65) according approach. Treatment efficacy, indicators (albumin [ALB], alanine aminotransferase [ALT], aspartate [AST]), factor indexes (tumour necrosis alpha [TNF-α] interferon gamma [IFN-γ]), hepatitis surface antigen [HBsAg] DNA levels compared among three groups. All followed up after treatment. According their prognosis, good (n 118) poor 66). Logistic regression analysis was performed patients. Results higher (92.31%) than that (8.82%) (78.82%) (p < 0.05). After HBsAg decreased groups Compared groups, exhibited significantly lower Besides, had ALT AST 0.05), ALB level demonstrated TNF-α IFN-γ Multivariate logistic identified family medical history as 0.001, odds ratio [OR] 3.614, 95% confidence interval [CI]: 1.685–7.750) therapy regimen protective 0.029, OR 0.135, CI: 0.022–0.815). Conclusion improves function, factors. In addition, this found are independent

Язык: Английский

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