Wilson病肝硬化并发肌肉减少症的危险因素及其对临床结局的影响

王玮琦; 魏涛华; 钱南南; 杨文明; 杨玉龙; 宋宇琪; 郝文杰; 杨悦; 席虎; 何伟

doi:10.12449/JCH251018

Wilson病肝硬化并发肌肉减少症的危险因素及其对临床结局的影响

DOI: 10.12449/JCH251018

王玮琦¹,
魏涛华^{1, 2, , ,},
钱南南^{1, 2},
杨文明^{1, 2},
杨玉龙^{1, 2},
宋宇琪¹,
郝文杰^{1, 2},
杨悦^{1, 2},
席虎^{1, 2},
何伟^{1, 2}

1.
安徽中医药大学第一附属医院神经内科，合肥 230006
2.
新安医学教育部重点实验室，合肥 230038

基金项目:

国家自然科学基金 (82305185);

国家自然科学基金 (U22A20366);

第七批全国老中医药专家学术经验继承项目 (Document No. ［2022］ 76 of the State Administration of Traditional Chinese Medicine);

杨文明全国名老中医药专家传承工作室 ;

安徽省自然科学基金青年项目 (2108085QH367);

安徽省高校自然科学基金重点项目 (KJ2021A0555);

安徽省高等学校省级质量工程项目 (2023jyxm1168);

安徽省中医药传承创新科研项目 (2024CCCX031);

安徽中医药大学青年科技英才培育项目 (2021qnyc08);

安徽中医药大学新安医学教育部重点实验室开放基金项目 (2020xayx12);

基于“中医药数字化转型发展”政策的中药临床疗效数字化评价研究 (YGZXKT2024180)

伦理学声明：本研究方案于2024年5月1日经由安徽中医药大学第一附属医院伦理委员会审批，批号：2024AH-60-02，所纳入患者均签署知情同意书。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：魏涛华、王玮琦负责课题设计，资料分析，撰写论文；杨玉龙、郝文杰、杨悦、席虎、何伟参与收集数据；钱南南、宋宇琪参与修改论文；魏涛华、杨文明负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
魏涛华， weitaohua@foxmail.com （ORCID： 0000-0003-3268-2491）

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出版历程
- 收稿日期: 2024-09-25
- 录用日期: 2024-12-10
- 出版日期: 2025-10-25

Risk factors for sarcopenia in patients with Wilson’s disease-related liver cirrhosis and their impact on clinical outcomes

Weiqi WANG¹,
Taohua WEI^{1, 2
, ,
,},
Nannan QIAN^{1, 2},
Wenming YANG^{1, 2},
Yulong YANG^{1, 2},
Yuqi SONG¹,
Wenjie HAO^{1, 2},
Yue YANG^{1, 2},
Hu XI^{1, 2},
Wei HE^{1, 2}

1.
Department of Neurology，The First Affiliated Hospital of Anhui University of Chinese Medicine，Hefei 230006，China
2.
Key Laboratory of Xin’an Medicine，Ministry of Education，Hefei 230038，China

Research funding:

National Natural Science Foundation of China (82305185);

National Natural Science Foundation of China (U22A20366);

The 7th Batch of National Inheritance Project of Academic Experience of Old TCM Experts (Document No. ［2022］ 76 of the State Administration of Traditional Chinese Medicine);

Yang Wenming’s National Inheritance Studio of Famous Old TCM Experts ;

Anhui Provincial Natural Science Foundation for Young Scientists (2108085QH367);

Anhui Provincial University Natural Science Foundation Key Project (KJ2021A0555);

Anhui Provincial Quality Engineering Project for Higher Education (2023jyxm1168);

Anhui Provincial TCM Inheritance and Innovation Scientific Research Project (2024CCCX031);

Anhui University of Chinese Medicine Young Science and Technology Talent Cultivation Project (2021qnyc08);

Anhui University of Chinese Medicine Xin’an Medicine Ministry of Education Key Laboratory Open Fund Project (2020xayx12);

Research on the Digital Evaluation of Clinical Efficacy of Traditional Chinese Medicine Based on the Policy of “Digital Transformation and Development of Traditional Chinese Medicine” (YGZXKT2024180)

More Information

Corresponding author: WEI Taohua， weitaohua@foxmail.com （ORCID：0000-0003-3268-2491）

摘要

摘要: 目的研究Wilson病肝硬化患者中肌肉减少症的发生情况，探讨肌肉减少症发生的危险因素及其对临床结局的影响。方法纳入2019年1月—2020年6月在安徽中医药大学第一附属医院接受治疗的140例Wilson病肝硬化患者，根据第三腰椎骨骼肌质量指数（L3 SMI）将患者分为肌肉减少症组和无肌肉减少症组。对纳入患者进行营养风险筛查、人体测量、血生化指标检测，比较两组相关指标的差异，筛选并发肌肉减少症的影响因素。随访36～48个月，比较两组患者生存状况、并发症发生情况。符合正态分布的计量资料2组间比较采用成组t检验；计数资料2组间比较采用χ²检验或Mann-Whitney U秩和检验。采用二元Logistic回归分析肌肉减少症的影响因素；通过单因素及多因素Cox回归分析影响Wilson病肝硬化患者预后的危险因素，绘制Kaplan-Meier生存曲线，采用Log-rank检验比较组间生存情况。结果 Wilson病肝硬化中并发肌肉减少症患者53例（37.9%），其身体质量指数（BMI）和L3 SMI明显低于无肌肉减少症患者（t值分别为10.550、3.982，P值均<0.001）。Logistic多因素回归分析结果显示，Wilson病肝硬化患者并发肌肉减少症的主要影响因素为年龄（OR=2.243，95%CI：1.196～4.208，P=0.012）、性别（OR=0.450，95%CI：0.232～0.872，P=0.018）、BMI（OR=0.126，95%CI：0.089～0.294，P<0.001）、肝性脑病（OR=8.367，95%CI：2.423～28.897，P<0.001）。并发肌肉减少症患者的病死率（χ²=6.158，P=0.019）以及感染（χ²=8.008，P=0.040）、反复腹/胸腔积液（χ²=17.742，P<0.001）、肝性脑病（χ²=4.338，P=0.039）的发生率均高于无肌肉减少症者，差异均有统计学意义。多因素Cox回归分析显示，肌肉减少症（HR=4.685，P=0.002）和肝性脑病（HR=19.156，P<0.001）为影响Wilson病肝硬化患者死亡的独立危险因素。Kaplan-Meier生存曲线提示，并发肌肉减少症的患者生存率显著下降（P=0.003）。结论肌肉减少症是Wilson病肝硬化患者营养不良的表现之一，其病死率、其他并发症的发生风险升高，对预后产生不良影响。男性患者、并发肝性脑病、BMI水平越低、年龄越大，肌肉减少症的发生风险越高。
- 肝豆状核变性 /
- 肝硬化 /
- 肌减少症 /
- 危险因素
Abstract: Objective To investigate the incidence rate of sarcopenia in patients with Wilson’s disease （WD）-related liver cirrhosis， as well as the risk factors for sarcopenia and their impact on clinical outcomes. Methods A total of 140 patients with WD-related liver cirrhosis who were treated in The First Affiliated Hospital of Anhui University of Chinese Medicine from January 2019 to June 2020， and according to the third lumbar skeletal muscle mass index （L3 SMI）， the patients were divided into sarcopenia group and non-sarcopenia group. Nutritional risk screening， anthropometric measurements， and blood biochemical tests were performed for the patients to identify the influencing factors for sarcopenia. The patients were followed up for 36 — 48 months， and survival status and complications were compared between the two groups. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the chi-square test and the Mann-Whitney U rank sum test were used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for sarcopenia， and univariate and multivariate Cox regression analyses were used to investigate the risk factors for the prognosis of patients with WD-related liver cirrhosis. The Kaplan-Meier survival curve was plotted， and the Log-rank test was used for comparison between groups. Results Among the 140 patients with WD-related liver cirrhosis， 53 （37.9%） developed sarcopenia， with significantly lower body mass index （BMI） and L3 SMI than the patients without sarcopenia （t=10.550 and 3.982， both P<0.001）. The multivariate Logistic regression analysis showed that age （odds ratio ［OR］=2.243， 95% confidence interval ［CI］： 1.196 — 4.208， P=0.012）， sex （OR=0.450， 95%CI： 0.232 — 0.872， P=0.018）， BMI （OR=0.126， 95%CI： 0.089 — 0.294， P<0.001）， and hepatic encephalopathy （OR=8.367， 95%CI： 2.423 — 28.897， P<0.001） were the main influencing factors for sarcopenia in patients with WD-related liver cirrhosis. Compared with the non-sarcopenia group， the sarcopenia group had significantly higher mortality rate （χ²=6.158， P=0.019） and significantly higher incidence rates of infection （χ²=8.008， P=0.040）， recurrent abdominal/pleural efflux （χ²=17.742， P<0.001）， and hepatic encephalopathy （χ²=4.338， P=0.039）. The multivariate Cox regression analysis showed that sarcopenia （hazard ratio ［HR］=4.685， P=0.002） and hepatic encephalopathy （HR=19.156， P<0.001） were independent risk factors for death in patients with WD-related liver cirrhosis. The Kaplan-Meier survival curve analysis showed a significant reduction in survival rate in the patients with sarcopenia （P=0.003）. Conclusion Sarcopenia is one of the manifestations of malnutrition in patients with WD-related liver cirrhosis， which increases the risk of mortality and other complications and has an adverse effect on prognosis. There is an increased risk of sarcopenia in male patients or patients with hepatic encephalopathy， a lower level of BMI or an older age.
- Hepatolenticular Degeneration /
- Liver Cirrhosis /
- Sarcopenia /
- Risk Factors

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图 1 试验流程图

Figure 1. Experimental flowchart

下载: 全尺寸图片幻灯片

注：在第三腰椎拍摄的腹部CT图像，红色表示骨骼肌；a为肌肉减少症患者（男），L3 SMI为40.82 cm²/m²；b为无肌肉减少症患者（男），L3 SMI为46.60 cm²/m²。

图 2 第三腰椎骨骼肌面积测量

Figure 2. Measurement of the third lumbar vertebra skeletal muscle area

下载: 全尺寸图片幻灯片

图 3 WD肝硬化患者Kaplan-Meier生存分析曲线

Figure 3. Kaplan-Meier survival analysis curve of patients with Wilson’s disease cirrhosis

下载: 全尺寸图片幻灯片

表 1 WD肝硬化并发肌肉减少症与无肌肉减少症患者相关指标比较

Table 1. Comparison of relevant indicators between the sarcopenia group and the non-sarcopenia group in WD patients complicated with liver cirrhosis

项目	无肌肉减少症（n=87）	并发肌肉减少症（n=53）	统计值	P值
年龄（岁）	36.9±11.1	45.3±11.1	t=4.340	<0.001
性别（例）			χ²=0.782	0.424
男	44	31
女	43	22
NRS-2002（例）			χ²=5.385	0.027
≥3分	71	50
<3分	16	3
并发症（例）
EV	76	42	χ²=2.896	0.112
胸/腹水	47	30	χ²=0.862	0.374
HE	6	12	χ²=5.213	0.027
Child-Pugh分级（例）			Z=-2.699	0.007
A级	21	4
B级	37	23
C级	29	26
L3 SMI（cm²/m²）	48.5±6.1	33.7±4.2	t=10.550	<0.001
TP（g/L）	63.54±8.42	62.44±8.87	t=0.736	0.463
Alb（g/L）	34.30±4.82	33.00±5.60	t=1.459	0.147
Hb（g/L）	112.91±21.40	104.45±20.46	t=0.351	0.726
BMI（kg/m²）	24.2±4.5	21.4±3.3	t=3.982	<0.001

下载: 导出CSV

表 2 WD肝硬化患者并发肌肉减少症影响因素的Logistic回归分析

Table 2. Logistic regression analysis of influencing factors of Wilson’s disease cirrhosis combined with sarcopenia

自变量	β值	SE	Wald	OR（95%CI）	P值
年龄	0.808	0.321	6.335	2.243（1.196～4.208）	0.012
性别	-0.799	0.338	5.600	0.450（0.232～0.872）	0.018
BMI	-1.823	0.306	35.409	0.126（0.089～0.294）	<0.001
HE	2.124	0.632	11.285	8.367（2.423～28.897）	<0.001
注：性别赋值女=1，男=0；HE赋值是=1，否=0。

下载: 导出CSV

表 3 WD肝硬化并发肌肉减少症患者在随访期间的临床结局

Table 3. Clinical outcomes during follow-up in Wilson’s disease cirrhosis combined with sarcopenia

组别	例数	死亡［例（%）］	反复胸/腹水［例（%）］	EV［例（%）］	感染［例（%）］	HE［例（%）］
无肌肉减少症	87	7（8.0）	29（33.3）	50（57.5）	13（14.9）	12（13.8）
并发肌肉减少症	53	13（24.5）	29（54.7）	41（77.4）	12（22.6）	13（24.5）
χ²值		6.158	17.742	1.182	8.008	4.338
P值		0.019	<0.001	0.337	0.040	0.039

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表 4 WD肝硬化患者死亡影响因素的Cox回归分析

Table 4. Cox regression analysis of factors affecting mortality in patients with Wilson’s disease cirrhosis

项目	β值	SE	Wald	HR	P值
单因素分析
肌肉减少症	4.396	1.663	6.985	81.117	0.008
年龄	1.096	0.495	4.897	2.991	0.027
性别	0.091	0.356	0.066	1.095	0.798
BMI	-1.568	0.442	12.582	0.209	<0.001
HE	1.543	0.491	9.879	4.679	0.002
EV	1.106	0.554	3.984	3.022	0.046
胸/腹水	0.245	0.388	0.400	1.278	0.527
多因素分析
肌肉减少症	1.544	0.498	9.633	4.685	0.002
HE	2.953	0.554	28.360	19.156	<0.001

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