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Functional healing
Ideal target for hepatitis B treatment
FC
Functional healing
The definition of functional cure (FC) was first proposed by United States scholars, when the definition required: persistent HBV DNA -, HBsAg -, cccDNA -, HBsAb +/-[1]. With the continuous in-depth research of clinical experts on diseases and therapeutic drugs, it has been found that cccDNA and integrated HBV DNA cannot be completely eliminated by existing treatment methods, so in the historical evolution of FC definition, cccDNA- is no longer required.
In 2015, a limited course of treatment was proposed, with minimal or no liver tissue lesions [2]; With the deepening of the study, the definition of FC has been gradually refined and standardized, and clinically measurable standards have been further defined in 2023 and 2024 to guide the outcome endpoints, namely, sustained HBsAg <0.05 IU/ml, HBV DNA <LLOQ, HBeAg(-), and liver histological improvement at 24 weeks after discontinuation of therapy [3-4].
In the historical process of the evolution of the definition of FC, HBsAg - this standard has always run through it, and it is of great significance to FC. A number of studies and explorations have been carried out on HBsAg removal by scholars at home and abroad. Real-world studies have shown that IFN can achieve HBsAg clearance in some dominant populations (HBsAg<1500 IU/ml) after limited treatment, and the patient's baseline HBsAg level is an important predictor, and the lower the baseline HBsAg level, the higher the HBsAg clearance after treatment. Baseline HBsAg level, baseline HBV DNA level, age, sex, genotype, and treatment strategy were independently correlated with HBsAg clearance obtained by Peg-IFNα treatment, and HBsAg (log10 IU/ml) and HBV DNA (log10 IU/ml) were more likely to obtain HBsAg clearance with lower HBsAg (log10 IU/ml). HBsAg levels and their reduction from baseline at weeks 12 and 24 of treatment, HBsAg decrease from baseline at week 12 ≥ 1 log10 IU/ml, and increased ALT at week 12 were independently correlated with HBsAg clearance obtained by PegIFNα-based treatment.
For patients with high baseline HBsAg levels, there is an urgent need for new drug development to meet the needs of treatment. At present, most of the patients enrolled in the new drugs under development are HBsAg>100IU/ml. Among the many investigational drugs, Bepirovirson is the first to enter the Phase 3 clinical study. Results from the Phase 2 study showed a 1.99 lg IU/ml decrease in HBsAg levels in patients treated with Bepirovirsen for 29 days [5]; Overall HBsAg clearance reached 35% at the end of 24 weeks of treatment, and stratified analysis found that patients with baseline HBsAg ≤ 3000 lU/ml and HBsAg ≤1000 had HBsAg clearance of 51% and 65%, respectively, at the end of 24 years of treatment. Among the patients included, baseline HBsAg > 100 IU/mL accounted for 69 percent [6].
Currently, a Phase 3 study is being conducted in multiple centers around the world [7-8]. The inclusion population was a patient population of 100 IU/mL < baseline HBsAg <3000 IU/mL, and the study was designed based on FC in accordance with the Technical Guidelines for Clinical Trials of Drugs for the Treatment of Chronic Hepatitis B Virus Infection [9]. The primary endpoint was the proportion of patients achieving functional cure 24 weeks after discontinuation of all treatments.
From the development of the definition of FC to the exploration of existing drugs and new drug research, it can be seen that it is the dominant population that is more likely to obtain functional cure, that is, "let some people get rich first", and gradually let a wider patient group achieve the goal of functional cure.
The Daystar project initiated by Professor Chen Yu of Beijing You'an Hospital affiliated to Capital Medical University is timely.
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About the Daystar project
Project Background
In August 2024, the Beijing Hepatobiliary Charity Foundation set up the [Daystar] project - "Real-world research on clinical cure of chronic hepatitis B at low surface antigen level", which aims to record and analyze the clinical characteristics of such patients, as well as the functional cure rate, liver cirrhosis and liver cancer incidence rate within 5~10 years through multi-center and prospective studies, so as to provide a scientific basis for clinical treatment and public health policies.
【How to Apply】
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The launch of the Daystar project has undoubtedly added new impetus and hope to explore the path of clinical cure for patients with chronic hepatitis B at low surface antigen levels. Relying on multi-center, prospective, in-depth observational studies, the project aims to deeply analyze the clinical characteristics, functional curative potential and long-term prognosis of this specific patient population, so as to lay a solid scientific foundation for the precise formulation of effective treatment strategies.
We warmly look forward to your participation, and under the guidance of the Daystar project, we will gather wisdom and strength to build a ray of hope, illuminate the road to recovery for chronic hepatitis B patients, and contribute to the grand blueprint of building a healthy China.
Source: Hepatobiliary Photography Platform