A nucleosome switch primes hepatitis B virus infection

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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New Perspectives on Development of Curative Strategies for Chronic Hepatitis B

Clinical Gastroenterology and Hepatology, Journal Year: 2023, Volume and Issue: 21(8), P. 2040 - 2050

Published: April 19, 2023

Language: Английский

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Toward a Functional Cure for Hepatitis B

Gut and Liver, Journal Year: 2024, Volume and Issue: 18(4), P. 593 - 601

Published: March 27, 2024

Current treatment of chronic hepatitis B virus (HBV) infection, pegylated interferon-α (pegIFN-α) and nucleos(t)ide analogue (NA), can suppress HBV replication, reverse liver inflammation fibrosis, decrease risks cirrhosis hepatocellular carcinoma, but surface antigen (HBsAg) loss is rare. Functional cure defined as undetectable HBsAg unquantifiable serum DNA for at least 24 weeks after a finite course therapy. This requires suppression replication viral protein production well restoration immune response to HBV. Direct-acting antivirals targeting entry, capsid assembly, secretion are in clinical trials. In parallel, modulatory therapies stimulate HBV-specific remove blockade being tested. Clinical trials direct-acting alone or have not been successful achieving cure. Recent combinations shown promising results particularly with that included pegIFN-α. These need be confirmed larger studies longer follow-up, further work needed develop simpler regimens fewer drugs administered orally safely. While there strong desire achieve cure, safety paramount new must provide incremental value compared standard care, which predominantly long-term NA

Language: Английский

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HBV and HBsAg strongly reshape the phenotype, function, and metabolism of DCs according to patients’ clinical stage

Hepatology Communications, Journal Year: 2025, Volume and Issue: 9(2)

Published: Jan. 29, 2025

Background: Hepatitis B is a liver infection caused by HBV. Infected individuals who fail to control the viral develop chronic hepatitis and are at risk of developing life-threatening diseases, such as cirrhosis or cancer. Dendritic cells (DCs) play important roles in immune response against HBV but functionally impaired patients with B. The underlying mechanisms involved HBV-induced DC dysfunctions remain be elucidated. Methods: We explored modulations HBsAg exposing blood-derived cDC1s, cDC2s, plasmacytoid DCs from healthy donors stimulating them toll-like receptor ligand. Their phenotypic functional features, well their metabolic profile, were analyzed through multiparametric flow cytometry multiplex assays further on patients’ samples. Results: found that deeply reshaped secretome Strikingly, we observed HBV-exposed secrete high levels CX3CL1 (fractalkine), chemokine responsible for attracting antiviral effectors site infection. exposure favored activation while drastically altering TRAIL expression ligand increasing secretion cytokines/chemokines tolerance. dampened metabolism subsets driving switches. Notably, relevance CX3CL1/CX3CR1 axis, TGF-β, disturbances was demonstrated within intrahepatic according disease stage. Conclusions: Our work brings new insights into immunomodulation induced DCs, which contribute responses progression toward chronicity.

Language: Английский

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What will it take to cure hepatitis B?

Hepatology Communications, Journal Year: 2023, Volume and Issue: 7(4)

Published: March 24, 2023

The current treatment of chronic HBV infection, pegylated interferon-α (pegIFNα) and nucleos(t)ide analog (NA), can suppress replication, reverse liver inflammation fibrosis reduce the risks cirrhosis, HCC, HBV-related deaths, but relapse is common when stopped before HBsAg loss. There have been major efforts to develop a cure for HBV, defined as sustained loss after finite course therapy. This requires suppression replication viral protein production restoration immune response HBV. Direct-acting antivirals targeting virus entry, capsid assembly, secretion are in clinical trials. Immune modulatory therapies stimulate adaptive or innate immunity and/or remove blockade being tested. NAs included most pegIFNα some regimens. Despite combination 2 more therapies, remains rare part because HbsAg be derived not only from covalently closed circular DNA also integrated DNA. Achievement functional will require eliminate silence In addition, assays differentiate source circulating determine recovery, well standardization improvement RNA hepatitis B core-related antigen, surrogate markers transcription, needed accurately assess target treatments according patient/disease characteristics. Platform trials allow comparison multiple combinations channel patients with different characteristics that likely succeed. Safety paramount, given excellent safety profile NA

Language: Английский

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Chronic Hepatitis B Infection: New Approaches towards Cure

Biomolecules, Journal Year: 2023, Volume and Issue: 13(8), P. 1208 - 1208

Published: Aug. 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.

Language: Английский

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High accuracy model for HBsAg loss based on longitudinal trajectories of serum qHBsAg throughout long-term antiviral therapy

Gut, Journal Year: 2024, Volume and Issue: 73(10), P. 1725 - 1736

Published: June 20, 2024

Hepatitis B surface antigen (HBsAg) loss is the optimal outcome for patients with chronic hepatitis (CHB) but this rarely occurs currently approved therapies. We aimed to develop and validate a prognostic model HBsAg on treatment using longitudinal data from large, prospectively followed, nationwide cohort.

Language: Английский

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TLR8 agonist selgantolimod regulates Kupffer cell differentiation status and impairs HBV entry into hepatocytes via an IL-6-dependent mechanism

Gut, Journal Year: 2024, Volume and Issue: 73(12), P. 2012 - 2022

Published: May 2, 2024

Objective Achieving HBV cure will require novel combination therapies of direct-acting antivirals and immunomodulatory agents. In this context, the toll-like receptor 8 (TLR8) agonist selgantolimod (SLGN) has been investigated in preclinical models clinical trials for chronic hepatitis B (CHB). However, little is known regarding its action on immune effectors within liver. Our aim was to characterise transcriptomic changes intercellular communication events induced by SLGN hepatic microenvironment. Design We identified TLR8 -expressing cell types human liver using publicly available single-cell RNA-seq data established a method isolate Kupffer cells (KCs). characterised cytokine KC profiles response SLGN. SLGN’s indirect effect evaluated hepatocytes treated with SLGN-conditioned media (CM) quantification parameters following infection. Pathways mediating were validated from HBV-infected patients. Results Hepatic expression takes place myeloid compartment. treatment KCs upregulated monocyte markers (eg, S100A12 ) downregulated genes associated identity SPIC ). Treatment SLGN-CM NTCP impaired entry. Cotreatment an interleukin 6-neutralising antibody reverted entry inhibition. Conclusion characterisation sheds light into programmes regulating activation. Furthermore, addition previously described infection adaptive immunity, we show that impairs Altogether, may contribute through remodelling intrahepatic microenvironment thus represent important component future combinations

Language: Английский

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Epidemiology of liver diseases: global disease burden and forecasted research trends

Science China Life Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 16, 2024

Language: Английский

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Past, present, and future of long-term treatment for hepatitis B virus

World Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 29(25), P. 3964 - 3983

Published: June 28, 2023

The estimated world prevalence of hepatitis B virus (HBV) infection is 316 million. HBV was identified in 1963 and nowadays a major cause cirrhosis hepatocellular carcinoma (HCC) despite universal vaccination programs, effective antiviral therapy. Long-term administration nucleos(t)ide analogues (NA) has been the treatment choice for chronic during last decades. NA shown good safety profile high efficacy controlling viral replication, improving histology, decreasing HCC incidence, decompensation, mortality. However, low probability surface antigen seroclearance made necessary an indefinite treatment. knowledge, recent years, about different phases cycle, new insights into role immune system have yielded increase therapeutic approaches. Consequently, several clinical trials evaluating combinations drugs with mechanisms action are ongoing promising results. This integrative literature review aims to assess knowledge advances from past B, present withdrawal, future perspectives combined molecules achieve functional cure.

Language: Английский

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