An Immunological Biomarker to Predict Hepatic Flares upon Nuc Therapy Discontinuation in Chronic Hepatitis B

Rivino, Laura; Bert, Nina Le; Gill, U.S.; Cheng, Yueming; Kunasegaran, Kamini; Tan, De-ming; Koh, Suk Bong; Hansi, Navjyot; Foster, Gena G.; Newell, Evan W.; Kennedy, P.T.F.; Bertoletti, Antonio

doi:10.1016/s0168-8278(16)01672-x

Cited by 2 publications

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“…CD8 + T cells play an important role in cellular immunity, which are considered to be effectors of virus clearance, killing HBV-infected hepatocytes with antigenic specificity restricted by MHC-I molecules (20). A few studies have revealed that in patients with acute hepatitis, activated CD8 + T cells targeting HBsAg are abundant, but in patients with chronic hepatitis B, the number of CD8 + T cells is reduced and their functions are impaired, leading to persistent viral replication (21,22). In the chimpanzee model infected with HBV, a considerable delay in viral clearance was observed by using CD8 + T cells blocking antibodies (23).…”

Section: Persistent Hbv Infection and Host Immune Response Persistent...mentioning

confidence: 99%

Hepatitis B functional cure and immune response

2022

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Hepatitis B virus (HBV) is a hepatotropic virus, which damage to hepatocytes is not direct, but through the immune system. HBV specific CD4+ T cells can induce HBV specific B cells and CD8+ T cells. HBV specific B cells produce antibodies to control HBV infection, while HBV specific CD8+ T cells destroy infected hepatocytes. One of the reasons for the chronicity of HBV infection is that it cannot effectively activate adoptive immunity and the function of virus specific immune cells is exhausted. Among them, virus antigens (including HBV surface antigen, e antigen, core antigen, etc.) can inhibit the function of immune cells and induce immune tolerance. Long term nucleos(t)ide analogues (NAs) treatment and inactive HBsAg carriers with low HBsAg level may “wake up” immune cells with abnormal function due to the decrease of viral antigen level in blood and liver, and the specific immune function of HBV will recover to a certain extent, thus becoming the “dominant population” for functional cure. In turn, the functional cure will further promote the recovery of HBV specific immune function, which is also the theoretical basis for complete cure of hepatitis B. In the future, the complete cure of chronic HBV infection must be the combination of three drugs: inhibiting virus replication, reducing surface antigen levels and specific immune regulation, among which specific immunotherapy is indispensable. Here we review the relationship, mechanism and clinical significance between the cure of hepatitis B and immune system.

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Section: Persistent Hbv Infection and Host Immune Response Persistent...mentioning

confidence: 99%

Hepatitis B functional cure and immune response

2022

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A meta-analysis of the antiviral activity of the HBV-specific immunotherapeutic TG1050 confirms its value over a wide range of HBsAg levels in a persistent HBV pre-clinical model

Sansas

Lélu

Evlachev

et al. 2018

Human Vaccines & Immunotherapeutics

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Pre-clinical models mimicking persistent hepatitis B virus (HBV) expression are seldom, do not capture all features of a human chronic infection and due to their complexity, are subject to variability. We report a meta-analysis of seven experiments performed with TG1050, an HBV-targeted immunotherapeutic,1 in an HBV-persistent mouse model based on the transduction of mice by an adeno-associated virus coding for an infectious HBV genome (AAV-HBV). To mimic the clinical diversity seen in HBV chronically infected patients, AAV-HBV transduced mice displaying variable HBsAg levels were treated with TG1050. Overall mean percentages of responder mice, displaying decrease in important clinical parameters i.e. HBV-DNA (viremia) and HBsAg levels, were 52% and 51% in TG1050 treated mice, compared with 8% and 22%, respectively, in untreated mice. No significant impact of HBsAg level at baseline on response to TG1050 treatment was found. TG1050-treated mice displayed a significant shorter Time to Response (decline in viral parameters) with an Hazard Ratio (HR) of 8.3 for viremia and 2.6 for serum HBsAg. The mean predicted decrease for TG1050-treated mice was 0.5 log for viremia and 0.8 log for HBsAg, at the end of mice follow-up, compared to no decrease for viremia and 0.3 log HBsAg decrease for untreated mice. For mice receiving TG1050, a higher decline of circulating viremia and serum HBsAg level over time was detected by interaction term meta-analysis with a significant treatment effect (p = 0.002 and p<0.001 respectively). This meta-analysis confirms the therapeutic value of TG1050, capable of exerting potent antiviral effects in an HBV-persistent model mimicking clinical situations.

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An Immunological Biomarker to Predict Hepatic Flares upon Nuc Therapy Discontinuation in Chronic Hepatitis B

Cited by 2 publications

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Hepatitis B functional cure and immune response

Hepatitis B functional cure and immune response

A meta-analysis of the antiviral activity of the HBV-specific immunotherapeutic TG1050 confirms its value over a wide range of HBsAg levels in a persistent HBV pre-clinical model

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