一项关于干扰素治疗慢性乙型肝炎合并代谢相关脂肪性肝病以实现临床治愈的前瞻性、多中心队列研究的研究方案。
A research protocol for a prospective, multicenter, cohort study on interferon therapy for chronic hepatitis B combined with metabolism-associated fatty liver disease to achieve clinical cure.
作者信息
Zhou Daqiong, Zhang Chao, Zhang Lu, Jia Jianru, Fu Junliang, Cao Zhenhuan
机构信息
Beijing Youan Hospital, Capital Medical University, Beijing, China.
The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
出版信息
Front Public Health. 2025 Mar 14;13:1546182. doi: 10.3389/fpubh.2025.1546182. eCollection 2025.
INTRODUCTION
The incidence of chronic hepatitis B (CHB) combined with metabolism-associated fatty liver disease (MAFLD) is increasing annually, and the presence of MAFLD may influence the clinical assessment of viral activity and transaminase levels. However, it remains unclear whether MAFLD impacts the achievement of clinical cure in CHB patients treated with polyethylene glycol interferon (Peg-IFN).
METHODS
A prospective cohort study was conducted to enroll patients with dominant CHB (on NA treatment, HBsAg <1,500 IU/mL, HBeAg negative, HBV DNA <10 IU/mL) and patients with dominant CHB combined with MAFLD, all of whom were treated with Peg-IFN. The study aimed to assess the efficacy and safety of Peg-IFN treatment and to elucidate the effect of MAFLD on achieving HBsAg clearance in these patients. Additionally, the study explored the T-lymphocyte characteristics of patients with CHB combined with MAFLD, analyzed the role of T-lymphocytes expressing inhibitory receptors in HBsAg clearance, and investigated the immunological mechanisms of HBsAg clearance through single-cell transcriptome sequencing technology.
ETHICS AND DISSEMINATION
Patients will be recruited at four medical centers in Beijing and Hebei, and written informed consent will be obtained to inform participants of the purpose of the study, potential risks, and benefits. Ethical approval has been granted for the study, which will focus on 48-week HBsAg clearance, and a detailed follow-up and adverse event monitoring plan has been developed.
STRENGTHS AND LIMITATIONS OF THIS STUDY
Strengths are that this study fills the gap in treatment strategies for patients with CHB combined with MAFLD and provides important treatment guidance to clinicians; the multicenter design may increase the diversity of the sample size, reduce the bias of single-center studies, and improve the external validity of the results. Limitations are that interferon therapy is often associated with side effects, which may lead to lower patient adherence and affect long-term follow-up and outcome monitoring of the study; the heterogeneity of the MAFLD population may have different effects on the efficacy of interferon therapy.
CLINICAL TRIAL REGISTRATION
http://www.chictr.org.cn/bin/project/edit?pid=231498, identifier ChiCTR2400084913.
引言
慢性乙型肝炎（CHB）合并代谢相关脂肪性肝病（MAFLD）的发病率逐年上升，MAFLD的存在可能会影响病毒活性和转氨酶水平的临床评估。然而，MAFLD是否会影响接受聚乙二醇干扰素（Peg-IFN）治疗的CHB患者实现临床治愈仍不清楚。
方法
进行了一项前瞻性队列研究，纳入以CHB为主（接受核苷（酸）类似物治疗，HBsAg<1500 IU/mL，HBeAg阴性，HBV DNA<10 IU/mL）的患者以及以CHB为主合并MAFLD的患者，所有患者均接受Peg-IFN治疗。该研究旨在评估Peg-IFN治疗的疗效和安全性，并阐明MAFLD对这些患者实现HBsAg清除的影响。此外，该研究探讨了CHB合并MAFLD患者的T淋巴细胞特征，分析了表达抑制性受体的T淋巴细胞在HBsAg清除中的作用，并通过单细胞转录组测序技术研究了HBsAg清除的免疫机制。
伦理与传播
将在北京和河北的四个医疗中心招募患者，并获得书面知情同意书，告知参与者研究目的、潜在风险和益处。该研究已获得伦理批准，将重点关注48周时的HBsAg清除情况，并制定了详细的随访和不良事件监测计划。
本研究的优势与局限性
优势在于本研究填补了CHB合并MAFLD患者治疗策略的空白，为临床医生提供了重要的治疗指导；多中心设计可能会增加样本量的多样性，减少单中心研究的偏差，并提高结果的外部有效性。局限性在于干扰素治疗通常伴有副作用，这可能导致患者依从性降低，并影响研究的长期随访和结果监测；MAFLD人群的异质性可能对干扰素治疗的疗效有不同影响。
临床试验注册
http://www.chictr.org.cn/bin/project/edit?pid=231498，标识符ChiCTR2400084913。
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