Fighting Amyotrophic Lateral Sclerosis by Protecting the Liver? A Prospective Cohort Study.

IF 8.1 1区医学 Q1 CLINICAL NEUROLOGY Annals of Neurology Pub Date : 2024-10-19 DOI:10.1002/ana.27115

Luyi Zhu, Yaojia Li, Xinyue Yu, Yinuo Chen, Junwei Zhang, Chunyang Pang, Jiali Xie, Lingfei Gao, Lihuai Du, Wen Cao, Dongsheng Fan, Can Cui, Huan Yu, Binbin Deng

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Abstract

Background: Previous studies have observed liver abnormalities in amyotrophic lateral sclerosis (ALS) patients. This study aimed to investigate whether early signs of liver disease, measured by magnetic resonance imaging-derived iron-corrected T1-mapping (cT1), are risk factors for developing ALS.

Methods: cT1 and proton density fat fraction were measured and automatically analyzed using LiverMultiScan® software. The Fibrosis-4 index was calculated using an established formula based on age and blood markers. Cox proportional hazard models were used to examine the relationship between liver disease, liver biomarkers, and incident ALS.

Results: In a cohort of 533,707 individuals from UK Biobank, 24 ALS cases were identified among 28,328 participants with liver disease during the follow-up period. Among a total of 33,959 individuals with complete liver imaging data, 15 incident ALS cases were observed during a median follow-up period of 5.6 years. Individuals with liver disease had a higher risk of developing ALS, with an adjusted hazard ratio of 7.35 (95% CI 4.47-12.09; p < 0.001). An increase in cT1 was also associated with a higher risk of ALS. After adjusting for age, sex, Townsend deprivation index, smoking status, alcohol intake frequency, body mass index, proton density fat fraction, Fibrosis-4, and metabolic syndrome, an increase in cT1 remained significantly associated with a higher risk of ALS, with an adjusted hazard ratio of 3.15 (95% CI 1.79-5.55) per 1-SD increase. Sensitivity analyses confirmed these robust results.

Interpretation: Liver disease activity, indicated by cT1, increases the risk of developing ALS, independent of metabolic syndrome, liver fat, or fibrosis. ANN NEUROL 2024.

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通过保护肝脏对抗肌萎缩性脊髓侧索硬化症？一项前瞻性队列研究

背景：先前的研究发现肌萎缩侧索硬化症（ALS）患者的肝脏存在异常。本研究旨在探讨通过磁共振成像衍生铁校正T1映射（cT1）测量的肝脏疾病早期症状是否是导致肌萎缩侧索硬化症的风险因素。方法：使用LiverMultiScan®软件测量并自动分析cT1和质子密度脂肪分数。纤维化-4指数是根据年龄和血液标记物的既定公式计算得出的。采用 Cox 比例危险模型研究肝脏疾病、肝脏生物标志物与 ALS 发病之间的关系：结果：在英国生物库的 533,707 人队列中，有 28,328 名参与者在随访期间患有肝病，其中发现了 24 例 ALS 病例。在中位随访期为5.6年的总共33959名有完整肝脏成像数据的参与者中，观察到15例ALS病例。肝病患者罹患 ALS 的风险较高，调整后的危险比为 7.35（95% CI 4.47-12.09；P 解释：以 cT1 为标志的肝病活动会增加 ALS 的发病风险，与代谢综合征、肝脏脂肪或纤维化无关。ann neurol 2024.

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.