Core Insights - The ENSURE II study results have been published in the peer-reviewed journal Nature Medicine, evaluating the efficacy and safety of the siRNA drug elebsiran in combination with PEG-IFNα for chronic hepatitis B treatment [1][2] - The study also explores the potential role of the therapeutic vaccine BRII-179 in enhancing immune response and increasing HBsAg clearance rates in patients [1] Group 1 - The ENSURE study was conducted in two parts, with the first part involving chronic HBV patients who had not previously received BRII-179, randomized to receive either 48 weeks of PEG-IFNα monotherapy or combination therapy with elebsiran [2] - In the second part, participants who had previously completed a study with elebsiran and BRII-179 were classified based on their anti-HBs peak levels and received 48 weeks of elebsiran combined with weekly PEG-IFNα treatment [2] Group 2 - Professor Jia Jidong, the lead investigator of the ENSURE study, emphasized the study's aim to provide scientific evidence for curative therapies for chronic hepatitis B and address key scientific questions [3] - Encouragingly, the 24-week follow-up data aligned with the results at the end of treatment, supporting the additional clinical benefits of elebsiran and indicating the potential new role of BRII-179 in activating the immune response in chronic HBV patients [3]

Core Insights - The core focus of the news is the publication of the ENSURE II study results, which evaluates the efficacy and safety of the siRNA drug elebsiran in combination with PEG-IFNα for the treatment of chronic hepatitis B virus (HBV) infection [1][2] Group 1: Study Overview - The ENSURE study was conducted in two parts, assessing chronic HBV patients with viral suppression [2] - In the first part, participants who had not received BRII-179 were randomly assigned to either 48 weeks of PEG-IFNα monotherapy or a combination treatment with elebsiran (administered every 4 weeks at doses of 200mg or 100mg) [2] - The second part involved participants who had previously received elebsiran combined with BRII-179, categorized based on their anti-HBs peak levels, and subsequently treated with elebsiran (100mg every 4 weeks) and weekly PEG-IFNα for 48 weeks [2] Group 2: Publication Details - The study results have been published in the peer-reviewed journal Nature Medicine, under the title "elebsiran and PEG-IFNα treatment for chronic hepatitis B virus infection: a partially randomized, open-label phase II clinical trial" [1] - The research also explores the potential role of the therapeutic vaccine BRII-179 in identifying immune responders and enhancing the HBsAg clearance rate [1]

Core Viewpoint - The study highlights the role of CD4⁺ T cells in reversing CD8⁺ T cell dysfunction induced by hepatocellular priming in chronic hepatitis B virus (HBV) infection, emphasizing IL-27 as a potential therapeutic target for immune intervention [4][11]. Group 1: CD4⁺ T Cells and CD8⁺ T Cell Dysfunction - CD4⁺ T cells activate Kupffer cells to reverse CD8⁺ T cell dysfunction, which is crucial for restoring HBV-specific CD8⁺ T cell function [4][10]. - The research indicates that IL-27 is essential for the recovery of CD8⁺ T cells, and exogenous IL-27 can restore their functionality [4][11]. Group 2: Mechanisms of T Cell Activation - CD8⁺ T cells can be activated directly in the liver, but often enter a dysfunctional state despite being able to proliferate [9]. - The study proposes a phased model where CD4⁺ T cell assistance occurs after CD8⁺ T cell activation, suggesting that CD4⁺ T cells can provide repair signals in non-lymphoid tissues like the liver [9][10]. Group 3: Implications for Treatment - The findings suggest that targeting IL-27 could be a viable strategy for immunotherapy in chronic HBV infection, as it plays a significant role in restoring CD8⁺ T cell function [11].

Core Insights - The 34th Asia-Pacific Association for the Study of the Liver (APASL 2025) conference highlighted the academic achievements of Hansoh Pharmaceutical's oral antiviral drug, TMF (Amitriptyline), which is the first original research drug for hepatitis B in China [1][2] - TMF demonstrated significant efficacy in chronic hepatitis B patients, with a 95% cumulative HBV DNA suppression rate and a 68% HBeAg seroconversion rate over five years, the highest among current NAs [1] - The drug's safety profile remained stable, with no new drug-related adverse events reported during the study period [1] Group 1 - TMF's Phase IV study showed sustained benefits for chronic hepatitis B patients, particularly in virological response and HBeAg seroconversion [1] - The cumulative incidence of virological resistance after five years of treatment with TMF was 0% [1] - The immunological mechanism study indicated TMF's potential to modulate T cell responses and reduce viral load, contributing to its antiviral efficacy [1] Group 2 - Over 20 additional studies related to TMF were presented, covering its application in various subpopulations, including the elderly, pregnant women, and patients with liver cirrhosis and liver cancer [2] - A systematic review and network meta-analysis indicated TMF's superiority in ALT normalization and delaying liver fibrosis progression compared to other new-generation NAs [2] - TMF was shown to have good maternal-fetal safety and efficacy in treating hepatitis B in pregnant women, successfully preventing HBV mother-to-child transmission [2]