How to achieve a functional cure for chronic hepatitis B infection

Clinical Liver Disease, Journal Year: 2024, Volume and Issue: 23(1)

Published: Jan. 1, 2024

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Language: Английский

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Serum sPD‐1 and sPD‐L1 as predictive biomarkers for HBsAg clearance in HBeAg‐negative CHB patients undergoing IFN‐based therapy

Alimentary Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 60(5), P. 593 - 603

Published: June 25, 2024

Summary Background and Aims For chronic hepatitis B (CHB) patients, there is still a need to improve surface antigen (HBsAg) clearance rates. This study aimed assess the predictive effectiveness of soluble programmed cell death‐1 (sPD‐1) death ligand‐1 (sPD‐L1) for HBsAg in HBeAg‐negative CHB patients undergoing peginterferon (Peg‐IFN)‐based antiviral treatment. Methods encompassed 280 treatment with Peg‐IFNα. Serum levels sPD‐1 sPD‐L1 were measured using ELISA kits at baseline, as well 12, 24 48 weeks. The primary endpoint was determination Logistic regression analysis employed identify predictors clearance. Results group demonstrated significantly lower serum compared non‐clearance group. While both groups exhibited an increase levels, only showed rise levels. Multivariate identified weeks, decline weeks combined use these indicators performance AUROC 0.907 (95% CI: 0.861–0.953, p < 0.001). Conclusions revealed inverse relationship between trends sPD‐1/sPD‐L1 during IFN NAs Moreover, magnitude reduction emerged significant

Language: Английский

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Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomics

eGastroenterology, Journal Year: 2024, Volume and Issue: 2(3), P. e100067 - e100067

Published: July 11, 2024

The intrahepatic processes associated with chronic hepatitis B (CHB), especially in the context of delta virus (HDV) and HIV co-infection, require a better understanding. Spatial transcriptomics can provide new insights into complex biological processes, guiding personalised treatments. Our aim is to evaluate this method characterising transcriptional landscape, cellular composition pathways liver biopsy samples from patients (HBV) HDV or co-infection.

Language: Английский

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Activating adaptive immunity by bispecific, T-cell engager antibodies bridging infected and immune-effector cells is a promising novel therapy for chronic hepatitis B

Antiviral Research, Journal Year: 2024, Volume and Issue: 229, P. 105972 - 105972

Published: July 30, 2024

Bispecific antibodies (bsAbs) are engineered immunoglobulins that combine two different antigen-binding sites in one molecule. BsAbs can be divided into molecular formats: IgG-like and non-IgG-like antibodies. Structural elements of each format have implications for engaging the immune system. T cell engager (TCEs) bsAbs designed to engage cells with target cells. TCEs applied not only cancer but also infectious disease therapy activate T-cell responses. In this review, we focus on current literature design use as an innovative strategy enhance adaptive antiviral We summarized novel cell-related immunotherapies a TCEs, developed treatment chronic hepatitis B. Chronic infection B virus (HBV) had death toll 1.1 million humans 2022, mainly due liver cirrhosis hepatocellular carcinoma developing more than 250 chronically infected. A curative approach is lacking. Combining therapies activating responses regarded most promising therapeutic curing HBV preventing sequelae infection. Attracting functionally intact HBV-specific and, therefore, yet been exposed regulatory mechanisms those at site very interesting could achieved by TCEs. Thus, redirecting toward HBV-positive represent treating HBV-associated carcinoma.

Language: Английский

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The significance of antibody to hepatitis B surface antigen in infection and clearance of hepatitis B virus

Human Vaccines & Immunotherapeutics, Journal Year: 2025, Volume and Issue: 21(1)

Published: Jan. 3, 2025

One of the key features chronic hepatitis B virus (HBV) infection is inability to mount sufficient and coordinated adaptive immune responses against HBV. Recent studies on HBV-specific cells antibody surface antigen (anti-HBs) have shed light their role in pathogenesis (CHB). Anti-HBs recognized as a protective marker, both for HBV clearance following vaccination, it also considered an important indicator functional cure CHB. Notably, impairment may be reversible. The restoration cell function, along with induction anti-HBs response, regarded pivotal terminating achieving cure. This article reviews significance HBV, discusses potential neutralizing antibodies therapeutic vaccines promising future strategies.

Language: Английский

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Prediction of cccDNA dynamics in hepatitis B patients by a combination of serum surrogate markers

PLoS Computational Biology, Journal Year: 2025, Volume and Issue: 21(1), P. e1012615 - e1012615

Published: Jan. 9, 2025

Quantification of intrahepatic covalently closed circular DNA (cccDNA) is a key for evaluating an elimination hepatitis B virus (HBV) in infected patients. However, quantifying cccDNA requires invasive methods such as liver biopsy, which makes it impractical to access the dynamics Although HBV RNA and core-related antigens (HBcrAg) have been proposed surrogate markers activity, they do not necessarily estimate amount cccDNA. Here, we employed recently developed multiscale mathematical model describing intra- intercellular viral propagation applied HBV-infected patients under treatment. We that can predict intracellular by use extracellular markers, including HBsAg, DNA, HBcrAg peripheral blood. Importantly, prediction over time was confirmed be well correlated with data quantified paired biopsy. Thus, our method combining classic emerging enables us decay undergoing

Language: Английский

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Differences in the intrahepatic expression of immune checkpoint molecules on T cells and natural killer cells in chronic HBV patients

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 15, 2025

Patients with chronic hepatitis B virus (HBV) infection are characterized by impaired immune response that fails to eliminate HBV. Immune checkpoint molecules (ICMs) control the amplitude of activation and function cells, which makes them key regulators response. We performed a multiparametric flow cytometry analysis ICMs determined their expression on intrahepatic lymphocyte subsets in untreated treated patients HBV comparison non-pathological liver tissue. The exhibited high accumulation PD-1+CD8+ T while frequencies 4-1BB+ natural killer (NK) TIM-3+CD8+ cells were highest phase. Our findings showed HBeAg status is linked distinct phenotype CD8+ NK ICMs, particularly 4-1BB. Importantly, antiviral treatment partially restored normal ICMs. Finally, we described important differences ICM between circulating patients. study shows clear depending clinical stage.

Language: Английский

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CD163 impairs HBV clearance in mice by regulating intrahepatic T cell immune response via an IL-10-dependent mechanism

Antiviral Research, Journal Year: 2025, Volume and Issue: 235, P. 106093 - 106093

Published: Jan. 22, 2025

Language: Английский

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Update on the treatment navigation for functional cure of chronic hepatitis B: expert consensus 2.0

Clinical and Molecular Hepatology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel national hepatologists published Consensus Statement on B. Currently, an international group has been assembled to evaluate research since publication original consensus, and collaboratively develop updated statements. The 2.0 was aimed update consensus with latest available studies, provide comprehensive overview current relevant scientific literatures regarding B, particular focus issues that not yet fully clarified. These cover definition its mechanisms barriers, effective roadmap achieve this endpoint, in surrogate biomarkers used measure efficacy or predict response, appropriate approach pursuing special populations, development emerging antivirals immunomodulators potential for curing statements primarily intended offer guidance clinicians their practice enhance rate

Language: Английский

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Revolutionizing Fixed-Dose Combinations with Long-Acting Microsphere

European Journal of Pharmaceutical Sciences, Journal Year: 2025, Volume and Issue: unknown, P. 107032 - 107032

Published: Feb. 1, 2025

Language: Английский

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