代谢功能障碍对慢性乙型肝炎核苷（酸）类似物治疗反应的影响：一项回顾性多中心REAL-B队列研究
Impact of metabolic dysfunction on treatment responses to nucleos(t)ide analogues in chronic hepatitis B: a retrospective multi-center REAL-B cohort study.
作者信息
Huang Rui, Jun Dae Won, Toyoda Hidenori, Hsu Yao-Chun, Trinh Huy, Nozaki Akito, Ishikawa Toru, Watanabe Tsunamasa, Uojima Haruki, Huang Daniel Q, Honda Takashi, Tanaka Yasuhito, Vutien Philip, Marciano Sebastián, Abe Hiroshi, Enomoto Masaru, Atsukawa Masanori, Takahashi Hirokazu, Tsuji Kunihiko, Itobayashi Ei, Takaguchi Koichi, Tsai Pei-Chien, Dai Chia-Yen, Huang Jee-Fu, Huang Chung-Feng, Yeh Ming-Lun, Yoon Eileen, Kim Sung Eun, Ahn Sang Bong, Kim Gi-Ae, Jung Jang Han, Jeong Soung Won, Oh Hyunwoo, Tseng Cheng-Hao, Ishigami Masatoshi, Chau Angela, Hsiao Tiffany, Maeda Mayumi, Yasuda Satoshi, Chuma Makoto, Ito Takanori, Kawashima Keigo, Liu Joanne Kimiko, Gadano Adrian, Kozuka Ritsuzo, Itokawa Norio, Inoue Kaori, Senoh Tomonori, Li Jie, Chuang Wan-Long, Cheung Ramsey, Wu Chao, Yu Ming-Lung, Nguyen Mindie H
机构信息
Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA.
Department of Infectious Disease, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
出版信息
EClinicalMedicine. 2025 Aug 11;87:103407. doi: 10.1016/j.eclinm.2025.103407. eCollection 2025 Sep.
BACKGROUND
Metabolic dysfunction is associated with liver disease but it is unclear if it would impact responses to antiviral treatment in chronic hepatitis B (CHB) patients.
METHODS
Using data from an international consortium of 4507 treatment-naïve CHB patients who initiated nucleos(t)ide analogues (NAs) between January 2004 and August 2024 from 32 centers and propensity-score matching (PSM) to balance the background of patients with and without metabolic disease (diabetes, obesity, dyslipidemia, or hypertension), we compared their biochemical (BR), virologic (VR), and complete (CR) response.
FINDINGS
More than half (54.8%) had at least one metabolic disease. Patients with metabolic disease (vs. no) were older and more likely male. In the PSM cohort of 893 pairs of patients, patients with metabolic disease had significantly lower 5-year cumulative BR (91.3% vs. 95.8%, < 0.001) and CR rates (81.8% vs. 87.4%, = 0.008), but similar VR (93.5% vs. 94.1%, = 0.65) and HBeAg seroconversion rates (27.0% vs. 29.7%, = 0.92). On multivariable Cox regression, metabolic disease was associated with lower BR (adjusted hazard ratio [aHR] 0.73, < 0.001) and CR (aHR 0.79, = 0.001), especially in those with ≥3 metabolic diseases (aHR 0.55 for BR; aHR 0.53 for CR, both < 0.001).
INTERPRETATION
The presence and number of metabolic diseases were significantly and incrementally associated with lower BR. Metabolic disease should be taken into consideration in the management of CHB patients receiving NAs treatment.
FUNDING
None.
背景
代谢功能障碍与肝脏疾病相关，但尚不清楚其是否会影响慢性乙型肝炎（CHB）患者对抗病毒治疗的反应。
方法
利用来自一个国际联盟的数据，该联盟包含4507例未经治疗的CHB患者，这些患者于2004年1月至2024年8月期间在32个中心开始使用核苷（酸）类似物（NA），并采用倾向评分匹配（PSM）来平衡有和没有代谢疾病（糖尿病、肥胖、血脂异常或高血压）患者的背景，我们比较了他们的生化（BR）、病毒学（VR）和完全（CR）反应。
研究结果
超过一半（54.8%）的患者至少患有一种代谢疾病。患有代谢疾病的患者（与未患代谢疾病的患者相比）年龄更大，且更可能为男性。在893对患者的PSM队列中，患有代谢疾病的患者5年累积BR显著更低（91.3%对95.8%，<0.001），CR率也更低（81.8%对87.4%，=0.008），但VR（93.5%对94.1%，=0.65）和HBeAg血清学转换率相似（27.0%对29.7%，=0.92）。在多变量Cox回归分析中，代谢疾病与更低的BR（调整后风险比[aHR]0.73，<0.001）和CR（aHR 0.79，=0.001）相关，尤其是在患有≥3种代谢疾病的患者中（BR的aHR为0.55；CR的aHR为0.53，两者均<0.001）。
解读
代谢疾病的存在和数量与更低的BR显著且呈递增关系。在管理接受NA治疗的CHB患者时应考虑代谢疾病。
资金来源
无。
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