Chronic Hepatitis B

Hepatitis B virus (HBV) infection is a major public health threat in China. At present, a functional cure, also known as clinical cure or sustained Hepatitis B surface antigen (HBsAg) loss, is recommended as the ideal endpoint of HBV treatment. However, HBsAg loss can be achieved in less than 10% of chronic hepatitis B (CHB) patients treated with current available antiviral drug interferonα (IFNα) or nucleos(t)ide analogues (NAs) monotherapy. With the support of the national major special funding for infectious diseases from "11th Five-Year Plan" to "13th Five-Year Plan", we have implemented a pioneer clinical study of sequential combination of IFNα therapy on NAs to treat NAs-treated CHB patients (ie. New Switch Study). This is the world's first clinical trial aiming to functional cure, which increased the rate of HBsAg loss to 15% in the overall population in our study, and to 30-50% among those with lower baseline HBsAg levels. How to further improve the HBsAg loss rate is an urgent issue for us. The key point of achieving functional cure is to reverse the HBV-specific T cell exhaustion and establish the long-term immune control against HBV infection. Programmed death-1(PD-1)/programmed death-ligand 1 (PD-L1) axis blockade has been demonstrated to reinvigorate exhausted CD8+ T cells, and would be a potential strategy to treat chronic HBV infection. In this study, a large multicenter prospective study will be performed to explore the safety and efficacy of a novel combination strategy involving immune checkpoint inhibitor (anti-PD-1/anti-PD-L1 antibody) and IFNα in CHB patients, observe the HBsAg loss rate in NA-treated CHB patients receiving this combination strategy, evaluate the potential of breaking immune tolerance by this strategy, and further assess its efficacy to further improve the clinical cure rate on the basis of New Switch Study. Based on New Switch Study, this study further attempts to reverse T cell exhaustion in CHB patients, explore a novel platform of combination therapy development for clinical cure, and ultimately increase the HBsAg loss rate to higher than 50% in overall patients. The implementation of the project is expected to reduce the burden of HBV infection in China and contribute to the goal of global elimination of hepatitis B and C by 2030 (WHO 2030).

This is a multicenter, randomized, double-blind, placebo-controlled Phase III study with an open-label extension. The purpose is to evaluate efficacy and safety in adult patients with chronic hepatitis B virus infection who have received at least 12 months of NAs therapy, to demonstrate that TQA3605 Tablets combined with oral nucleos(t)ide analogues can improve efficacy with satisfactory safety profile compared with oral nucleos(t)ide analogues alone in this population. Approximately 930 adult patients with chronic hepatitis B virus infection who have received at least 12 months of NAs therapy are planned to be enrolled in this study.

This single-center comparative cross-sectional study includes a prospective longitudinal follow-up cohort. At least 400 subjects from the "Everest Project" cohort will be enrolled into four groups: clinical-cure, non-cure, relapse, and healthy control. Data will be collected via online/offline questionnaires with internationally-standardized scales. This study aims to first systematically characterize the psychosocial value of chronic hepatitis B clinical cure, advance the shift from biomedical to biopsychosocial holistic health model, and provide scientific evidence for patient-management optimization and stigma-reduction public-health policy-making.

The goal of this observational study is to determine the prevalence of hepatitis D virus (HDV) and the distribution of the HDV genotype in patients with chronic hepatitis B infection. It will also identify factors related to hepatitis D virus infection, such as characteristics of the study sample, vaccination history, drug use affecting hepatitis, family factors, environment, and lifestyle. This study will be conducted at Tam Anh General Hospital, Bach Mai Hospital and Tam Anh TP. Ho Chi Minh General Hospital. Participants will be interviewed directly through a questionnaire to collect some information related to epidemiological risk factors. A blood sample will also be collected.

Hepatitis B virus (HBV) infection is a major public health threat in China. At present, a functional cure, also known as clinical cure or sustained Hepatitis B surface antigen (HBsAg) loss, is recommended as the ideal endpoint of HBV treatment. However, HBsAg loss can be achieved in less than 10% of chronic hepatitis B (CHB) patients treated with current available antiviral drug interferon (IFNα) or nucleos(t)ide analogues (NAs) monotherapy. With the support of the national major special funding for infectious diseases from "11th Five-Year Plan" to "13th Five-Year Plan", we have implemented a pioneer clinical study of sequential combination of IFNα therapy on NAs to treat NAs-treated CHB patients (ie. New Switch Study). This is the world's first clinical trial aiming to functional cure, which increased the rate of HBsAg loss to 15% in the overall population in our study, and to 30-50% among those with lower baseline HBsAg levels. How to further improve the HBsAg loss rate is an urgent issue for us. The key point of achieving functional cure is to reverse the HBV-specific T cell exhaustion and establish the long-term immune control against HBV infection. (Programmed death-1) PD-1/programmed death-ligand 1 (PD-L1) axis blockade has been demonstrated to reinvigorate exhausted CD8+ T cells, and would be a potential strategy to treat chronic HBV infection. In this study, a large multicenter prospective study will be performed to explore the safety and efficacy of a novel combination strategy involving immune checkpoint inhibitor (anti-PD-1/anti-PD-L1 antibody) and IFNα in CHB patients, observe the HBsAg loss rate in NA-treated CHB patients receiving this combination strategy, evaluate the potential of breaking immune tolerance by this strategy, and further assess its efficacy to further improve the clinical cure rate on the basis of New Switch Study. Based on New Switch Study, this study further attempts to reverse T cell exhaustion in CHB patients, explore a novel platform of combination therapy development for clinical cure, and ultimately increase the HBsAg loss rate to higher than 50% in overall patients. The implementation of the project is expected to reduce the burden of HBV infection in China and contribute to the goal of global elimination of hepatitis B and C by 2030 (WHO 2030).

Hepatitis B virus (HBV) infection is a major public health threat in China. At present, a functional cure, also known as clinical cure or sustained Hepatitis B surface antigen (HBsAg) loss, is recommended as the ideal endpoint of HBV treatment. However, HBsAg loss can be achieved in less than 10% of chronic hepatitis B (CHB) patients treated with current available antiviral drug interferon (IFNα) or nucleos(t)ide analogues (NAs) monotherapy. With the support of the national major special funding for infectious diseases from "11th Five-Year Plan" to "13th Five-Year Plan", we have implemented a pioneer clinical study of sequential combination of IFNα therapy on NAs to treat NAs-treated CHB patients (ie. New Switch Study). This is the world's first clinical trial aiming to functional cure, which increased the rate of HBsAg loss to 15% in the overall population in our study, and to 30-50% among those with lower baseline HBsAg levels. How to further improve the HBsAg loss rate is an urgent issue for us. The key point of achieving functional cure is to reverse the HBV-specific T cell exhaustion and establish the long-term immune control against HBV infection. Programmed death-1 (PD-1)/ programmed death-ligand 1 (PD-L1) axis blockade has been demonstrated to reinvigorate exhausted CD8+ T cells, and would be a potential strategy to treat chronic HBV infection. In this study, a large multicenter prospective study will be performed to explore the safety and efficacy of a novel combination strategy involving immune checkpoint inhibitor (anti-PD-1 antibody) in CHB patients, observe the HBsAg loss rate in NA-treated CHB patients receiving this combination strategy, evaluate the potential of breaking immune tolerance by this strategy, and further assess its efficacy to further improve the clinical cure rate on the basis of New Switch Study. Based on New Switch Study, this study further attempts to reverse T cell exhaustion in CHB patients, explore a novel platform of combination therapy development for clinical cure, and ultimately increase the HBsAg loss rate to higher than 50% in overall patients. The implementation of the project is expected to reduce the burden of HBV infection in China and contribute to the goal of global elimination of hepatitis B and C by 2030 (WHO 2030).

This study is a Phase Ib, multicenter randomized, double-blind, dose-escalation, placebo-controlled trial designed to evaluate the safety, tolerability, PK, and PD profiles of multiple-dose ACT500 in participants with metabolic dysfunction-associated steatotic liver disease (MASLD) complicated with chronic hepatitis B (CHB). The trial plans to enroll 24 participants with MASLD complicated with CHB across three dose cohorts initially, each consisting of 8 participants who will receive oral ACT500 tablets once daily.

This is a prospective, multicenter, randomized, open-label controlled clinical trial designed to evaluate the efficacy and safety of a sequential treatment strategy incorporating a PD-1 antibody and pegylated interferon-α (Peg-IFNα) in patients with chronic hepatitis B receiving stable nucleos(t)ide analogue (NA) therapy.

Hepatitis B virus (HBV) infection is a major public health threat in China. At present, a functional cure, also known as clinical cure or sustained Hepatitis B surface antigen (HBsAg) loss, is recommended as the ideal endpoint of HBV treatment. However, HBsAg loss can be achieved in less than 10% of chronic hepatitis B (CHB) patients treated with current available antiviral drug interferon (IFNα) or nucleos(t)ide analogues (NAs) monotherapy. With the support of the national major special funding for infectious diseases from "11th Five-Year Plan" to "13th Five-Year Plan", we have implemented a pioneer clinical study of sequential combination of IFNα therapy on NAs to treat NAs-treated CHB patients (ie. New Switch Study). This is the world's first clinical trial aiming to functional cure, which increased the rate of HBsAg loss to 15% in the overall population in our study, and to 30-50% among those with lower baseline HBsAg levels. How to further improve the HBsAg loss rate is an urgent issue for us. The key point of achieving functional cure is to reverse the HBV-specific T cell exhaustion and establish the long-term immune control against HBV infection. (Programmed death-1) PD-1/programmed death-ligand 1 (PD-L1) axis blockade has been demonstrated to reinvigorate exhausted CD8+ T cells, and would be a potential strategy to treat chronic HBV infection. In this study, a large multicenter prospective study will be performed to explore the safety and efficacy of a novel combination strategy involving immune checkpoint inhibitor (anti-PD-1 antibody) and IFNα in CHB patients, observe the HBsAg loss rate in NA-treated CHB patients receiving this combination strategy, evaluate the potential of breaking immune tolerance by this strategy, and further assess its efficacy to further improve the clinical cure rate on the basis of New Switch Study. Based on New Switch Study, this study further attempts to reverse T cell exhaustion in CHB patients, explore a novel platform of combination therapy development for clinical cure, and ultimately increase the HBsAg loss rate to higher than 50% in overall patients. The implementation of the project is expected to reduce the burden of HBV infection in China and contribute to the goal of global elimination of hepatitis B and C by 2030 (WHO 2030).

Exploring the safety and efficacy of the therapy combining immune checkpoint inhibitors (anti-PD-L1 monoclonal antibody, ASC22) and pegylated interferon alfa (Peg-IFNα) in patients with CHB. Exploring new combination therapeutic schemes for hepatitis B cure, and raising the overall clinical cure rate to more than 50% without screening specific advantageous groups.

Achieving a functional cure for chronic hepatitis B (CHB) is largely hindered by the irreversible functional exhaustion and immune tolerance of hepatitis B virus (HBV)-specific CD8 positive T (CD8+ T) cells. In investigators previous studies, an in vivo Clustered Regularly Interspaced Short Palindromic Repeat(CRISPR) screen identified ANKRD11 for the first time as an "epigenetic brake" on CD8+ T-cell effector function. Loss of ANKRD11 markedly enhanced the expansion, effector function, and viral clearance capacity of HBV-specific T cells. Based on these findings, investigators hypothesize that ANKRD11 regulates the epigenetic program of T-cell exhaustion by restricting the activity of AP-1 family transcription factors, and that targeting ANKRD11 can reverse T-cell dysfunction and overcome immune tolerance. This project will: (1) elucidate the epigenetic mechanisms by which ANKRD11 regulates T-cell exhaustion using conditional knockout mouse models and multi-omics approaches; (2) evaluate how ANKRD11 deficiency reshapes the differentiation trajectory and antiviral function of HBV-specific T cells in models of chronic HBV infection; and (3) develop a combinatorial gene-editing strategy integrating "release of the brake" with "stepping on the accelerator" to generate enhanced T Cell Receptor-T cell Therapy(TCR-T) cells and evaluate their efficacy and safety in humanized mouse models. The study is expected to define a novel mechanism by which ANKRD11 regulates T-cell exhaustion, establish an enhanced TCR-T therapeutic strategy, and provide a potential approach toward achieving a functional cure for chronic HBV infection.

Mother-to-child transmission (MTCT) is still the main transmission route of HBV in high-endemic areas, such as China, sub-Saharan Africa, etc. Some infants born of mothers with high HBV DNA load (≥2×10\^5 IU/ml) are still infected with HBV even if these infants receive the combined immunization on time. Therefore, guidelines including AASLD and EASL recommend that pregnant women with high HBV DNA load should take antiviral drugs (tenofovir disoproxil fumarate or telbivudine) to reduce MTCT of HBV from gestation 24-28 weeks. However, side effects of TDF on infants are reported. For example, neutropenia and the decrease of bone mineral density are found in early age infants who are ever exposed to TDF during their fetal life. Tenofovir alafenamide (TAF), a new prodrug of tenofovir (TFV), has a higher antiviral potency, a higher peripheral blood mononuclear cell (PBMC) intracellular tenofovir diphosphate (TFV pp) level and a lower plasma TFV concentration. As the successor of TDF, the dose of TAF that is took orally every day is approximately 1/10 of TDF. TAF has a much lower risk of kidney toxicity and has almost no effect on the bone mineral density. TAF has been approved and recommended as the first-line drug to treat patients with chronic hepatitis B (CHB) by AASLD, EASL, etc. However, there are relatively few data of TAF on pregnancies with high HBV DNA load. It is urgently to clarify the safety and efficacy of TAF on interrupting MTCT of HBV in pregnancies with high HBV DNA load. In the present study, the investigators enroll middle/late pregnancies with high HBV DNA load(≥2×10\^5 IU/ml). The participants are randomly divided into two groups. Then the participants are treated with TAF or TDF respectively. All enrolled participants are followed-up for 2 years. Objectives of the present study are as follows: A. To clarify safety and efficacy of TAF on interrupting MTCT of HBV in middle/late pregnancies with high HBV DNA load. B. To clarify effects of TAF on obstetric complications in middle/late pregnancies with CHB. C. To clarify effects of TAF on birth defects of infants born in mothers with CHB. D. To clarify the change of virology and biochemistry indexes in women with CHB during pregnancy and postpartum. E. To clarify effects of TAF treatment on participants. F. To clarify growth parameters of the infants exposed to TAF during their fetal life. G. To clarify the pharmacokinetics of TAF in pregnant populations.

This study is a prospective, open-label, multicenter long-term follow-up study to evaluate the durability of virologic response in subjects with chronic hepatitis B previously treated with AHB-137 injection.

This prospective multicenter observational study evaluates the performance of a structured hepatocellular carcinoma (HCC) surveillance program in patients at increased risk of developing liver cancer. Participants will undergo routine surveillance with semiannual abdominal ultrasound reported using the Ultrasound Liver Imaging Reporting and Data System (US LI-RADS) and serum alpha-fetoprotein (AFP) testing as part of standard clinical care. The study aims to assess HCC detection rates, stage at diagnosis, detection of other hepatic malignancies, and the time intervals between detection, diagnosis, and treatment in a real-world setting. Approximately 300 participants will be enrolled and followed for up to 36 months.

This is an open-label, multicenter, Phase 2 study designed to evaluate the efficacy and safety of AHB-137 injection in participants with chronic hepatitis B (CHB) with low hepatitis B surface antigen (HBsAg) levels.

This study is a randomized, double-blind, placebo-controlled, multicenter phase 2 study to assess the efficacy and safety of AHB-137 injection in treatment-naïve participants with chronic hepatitis B.

This is a randomized, open-label, multicenter phase II study to evaluate the efficacy and safety of AHB-137 injection in combination with other hepatitis B drugs in participants with HBeAg-negative CHB treated with NAs.

The purpose of this study is to determine the disease progression in CHB/NAFLD compared with CHB and NAFLD including liver cirrhosis, cirrhotic complications and hepatocellular carcinoma (HCC).

A clinical study evaluating the pharmacokinetic characteristics and safety of AHB-137 injection in participants with mild to moderate liver dysfunction and those with normal liver function.

A randomized, double-blind, placebo-controlled Phase IIa clinical study to evaluate the safety and efficacy of GST-HG131/GST-HG141 tablets in patients with chronic hepatitis B

The research plan aims to evaluate the consistency of the digital PCR-based hepatitis B virus nucleic acid quantification technique with the existing Roche qPCR-based detection method. Approximately 200 samples of residual serum from patients with chronic hepatitis B, covering high, medium, low, and those below the Roche lower limit concentration or undetectable, will be collected. The two methods will be used for parallel testing. The main objective is to evaluate the quantitative consistency of the two methods within the quantifiable range of Roche (≥ 20 IU/mL); the secondary objectives include evaluating the qualitative detection rate of samples with concentrations below 20 IU/mL or undetectable nucleic acid.

This study is an open-label, ascending dose phase 1b/2a trial to assess the safety and immunogenicity of a heterologous protein prime/MVA boost therapeutic hepatitis B vaccine in patients with chronic HBV who are virally suppressed with oral anti-viral therapies.

Persons with chronic hepatitis B (HBV) infection and active viremia are infectious and may transmit virus to others through blood/body fluid exposure. Immune tolerant treatment naive persons with hepatitis B infection express anxiety regarding disclosure of their infection status and significant fear of transmission to their partners leading to social isolation and impact on their personal lives. This study will provide data correlating serum and body fluid viral levels in persons with chronic hepatitis B infection not on therapy and those with viral suppression on long-term anti-retroviral therapy (ART) that may support the concept of "Undetectable=Untransmissible" (U=U) in patients with chronic hepatitis B.

Adherence to chronic Hepatitis B (HBV) treatment and regular follow-up visits is essential for preventing dangerous complications, yet adherence rates in Vietnam remain low due to barriers in patient awareness and geographic conditions. Digital health solutions, particularly mobile applications, have shown potential as tools for supporting patients in proactive disease management. The HBVCare mobile application was developed to provide features such as medication reminders, storage of lab results, and health education to improve treatment adherence and clinical outcomes. The investigators are conducting a multicenter, randomized controlled trial at Hoang Long Clinic and Hanoi Medical University Hospital to evaluate the effectiveness of HBVCare. Patients are randomized into either a control group receiving standard care and an intervention group using the HBVCare app, with patient adherence and related factors assessed after three months of treatment.

This is a multicenter, single-arm, open-label, phase IIIb extension clinical trial designed to evaluate the long-term safety and tolerability of GST-HG141 (nerlecovir, 50 mg BID) in combination with nucleos(t)ide analogues (NAs) in patients with chronic hepatitis B (CHB) who completed 48 weeks of treatment in the phase III study (GST-HG141-III-01), did not discontinue prematurely, had an overall medication compliance rate of ≥80%, and were willing to continue treatment. A maximum of 578 eligible participants will be enrolled at 64 centers, including those who completed the preceding study, had ALT ≤5× upper limit of normal (ULN), and had no severe comorbidities (e.g., decompensated cirrhosis, other viral infections, or malignant tumors)