HBx protein as a therapeutic target for functional cure of hepatitis B virus infection

Virology, Journal Year: 2025, Volume and Issue: 604, P. 110438 - 110438

Published: Jan. 31, 2025

Language: Английский

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Impact of Metformin on HBV Replication: No Evidence of Suppression in vitro

Published: Jan. 1, 2025

Language: Английский

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Impact of metformin on HBV replication: no evidence of suppression in vitro

Journal of Clinical Virology, Journal Year: 2025, Volume and Issue: unknown, P. 105781 - 105781

Published: March 1, 2025

Language: Английский

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The Intrinsically Disordered Region of HBx and Virus–Host Interactions: Uncovering New Therapeutic Approaches for HBV and Cancer

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3552 - 3552

Published: April 10, 2025

Human viral infections remain a significant global health challenge, contributing to substantial number of cancer cases worldwide. Among them, with oncoviruses such as hepatitis B virus (HBV) and C (HCV) are key drivers hepatocellular carcinoma (HCC). Despite the availability an effective HBV vaccine since 1980s, millions chronically infected due persistence covalently closed circular DNA (cccDNA) reservoir in hepatocytes. Current antiviral therapies, including nucleos(t)ide analogs interferon, effectively suppress replication but fail eliminate cccDNA, underscoring urgent need for innovative therapeutic strategies. Direct-acting agents (DAAs), which have revolutionized HCV treatment high cure rates, offer promising model therapy. A particularly attractive target is intrinsically disordered region (IDR) HBx protein, regulates cccDNA transcription, replication, oncogenesis by interacting host proteins. DAAs targeting these interactions could inhibit persistence, oncogenic signaling, overcome resistance. This review highlights potential HBx-directed complement existing offering renewed hope functional reduced risk.

Language: Английский

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Impact of hepatitis B surface antigen quantification on achieving a functional cure in patients with chronic hepatitis B: A systematic review and meta-analysis

Annals of Hepatology, Journal Year: 2025, Volume and Issue: unknown, P. 101921 - 101921

Published: April 1, 2025

Baseline hepatitis B surface antigen (HBsAg) levels are associated with the likelihood of achieving HBsAg loss which defines functional cure. However, optimal cut-offs for predicting have not been systematically investigated." Therefore, in this systematic review and meta-analysis, we evaluated impact baseline on a cure patients chronic (CHB). We searched PubMed, Embase, Cochrane Library up to December 31, 2023, identify studies comparing combination therapy nucleos(t)ide analogues (NAs) conventional/pegylated interferon (IFN) versus monotherapy. pooled proportion among stratified by different 75th percentile other clinical characteristics. included 24 3,446 participants. At end treatment, recruiting below 500 1000 IU/mL had highest proportions group, reaching 14% (95% CI: 9%-21%) 17% 10%-24%), respectively. One-year IFN-NAs treatment achieved higher (9%, 95% 6%-12%) than six-month (1%, 0%-2%). Patients normal alanine transaminase (ALT) (11%, 6%-17%) those elevated ALT (4%, 2%-7%). Meta-regression indicated positive association between male percentage loss. The thresholds would be 500∼1000 IU/mL, represents high-response subpopulation currently available therapy.

Language: Английский

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Recurrence risk factors for chronic hepatitis B virus-infected patients who achieve functional cure with pegylated interferon-α-2b-based therapy: a multicenter pilot study

Virology Journal, Journal Year: 2025, Volume and Issue: 22(1)

Published: May 19, 2025

Hepatitis B surface antigen (HBsAg) clearance is an achievable treatment endpoint for chronic hepatitis virus (HBV)-infected patients. Pegylated interferon-α (PEG-IFN-α) induces higher rate of HBsAg than nucleos(t)ide analogues. However, the influencing factors associated with recurrence have not been fully elucidated. The aim this study was to evaluate risk in HBV-infected patients who achieved functional cure PEG-IFN-α-2b-based treatment. A multicenter retrospective conducted. All received therapy, HBV DNA negativity and clearance, were followed-up at least 48 weeks after discontinuation medications. demographic data, as well virological, serological, biochemical indicators, collected baseline, therapy cessation, during followed-up. Logistic regression analysis subsequently performed. total 101 loss enrolled. median time 24.00 (14.50, 37.50) weeks, consolidation 11.00 (0.00, 24.00) weeks. found 16 a 70.00 (48.00, 96.00) week follow-up, cumulative 15.84%. platelet count slightly increased whereas shorter elevated appearance anti-HBs presented robustly reduced both cessation No positivity or occurrence end-stage liver disease observed 15.84% medications therapy. presence risk. This trial part ZhuFeng Project (ClinicalTrials.gov, identifier NCT04035837) E-Cure Study NCT05182463).

Language: Английский

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Functional cure of chronic hepatitis B-hope or hype?

World Journal of Hepatology, Journal Year: 2024, Volume and Issue: 16(9), P. 1199 - 1205

Published: Sept. 23, 2024

Chronic hepatitis B constitutes a substantial disease burden worldwide. The steps advocated by the World Health Organization in 2016 to eradicate 2030 has failed achieve significant progress, especially with respect immunization coverage and linkage care. lack of governmental public awareness regarding long-term implications cause underfunding developmental projects. presently approved treatment modalities have limited efficacy complete viral eradication, hence need for newer molecules functional cure (sustained undetectable surface antigen (HBsAg) virus DNA peripheral blood after finite period therapy). However, preliminary results from trials novel therapies show their inadequacy this end themselves but better performance low baseline serum HBsAg nucleos(t)ide analogues (NA) which be combined with/without pegylated interferon as an immunomodulator. Such therapy is cost adverse events incremental benefit over standard care (long-term NA therapy) drug toxicities, making development process tenuous. Thus, while such continue tested, strategies should still focus on prevention transmission non-pharmaceutical measures, vaccination increasing

Language: Английский

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Multiomics Analyses Reveal that Fatty Acid Metabolism and TCA Cycle Contribute to the Achievement of Functional Cure in Chronic Hepatitis B

Journal of Proteome Research, Journal Year: 2024, Volume and Issue: 24(1), P. 268 - 281

Published: Dec. 10, 2024

Peg-IFNα is one of the current therapeutic strategies for Hepatitis B virus (HBV) seroclearance. Nevertheless, underlying mechanisms are not yet adequately understood. The objective this study was to explore potential using multiomics approach. For first time, we revealed transcriptomic, proteomic, and metabolomic characterizations Peg-IFNα-induced HBsAg We found that caused significant changes during treatment. Patients who achieved seroclearance were characterized as having decreased transcriptional activity genes involved in fatty acid metabolism glycolysis/gluconeogenesis pathway, with up-regulated expression degradation-related proteins. Consistently, mitochondrial TCA cycle metabolites, including citric, isocitric, malic acids, significantly elevated patients also observed NK cell-mediated cytotoxicity, positive regulation cell activation, immunoglobulin production, T receptor complex functional-cured patients. Conversely, metabolites associated unsaturated biosynthesis increased persistent patients, production down-regulated after 48 weeks Our findings provided valuable resources better understand process shed new light on pathways facilitate higher functional cure rates CHB.

Language: Английский

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Core protein inhibitors: Opportunities and challenges at the forefront of hepatitis B cure: Editorial on “Phase 1 trial of the safety, pharmacokinetics, and antiviral activity of EDP-514 in untreated viremic chronic hepatitis B patients”

Clinical and Molecular Hepatology, Journal Year: 2024, Volume and Issue: 30(4), P. 692 - 694

Published: May 14, 2024

Language: Английский

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Therapeutic Vaccination in Chronic Hepatitis B: A Systematic Assessment by the HeberNasvac Therapeutic Vaccine Team

Published: Aug. 19, 2024

The immune system is central in controlling acute hepatitis B infection and patients resolving chronic (CHB). Given that 221 million (75%) of CHB reside low- middle-income countries, developing a vaccine with therapeutic properties represents rational cost-effective approach more than romantic endeavor. This review systematically analyses the critical variables related to safety, efficacy, effectiveness treatments. HeberNasvac's experience revisited address challenges potentialities vaccines, as well current roadblocks research development, registration, large-scale implementation.

Language: Английский

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