代谢相关脂肪性肝病与睡眠障碍的关系

吕佳慧; 李晓飞; 郭莲怡

doi:10.3969/j.issn.1001-5256.2021.12.024

代谢相关脂肪性肝病与睡眠障碍的关系

DOI: 10.3969/j.issn.1001-5256.2021.12.024

锦州医科大学研究生培养基地(盘锦市中心医院) 消化内科，辽宁盘锦 124000

基金项目:

辽宁省自然科学基金 (JYTQN2020031)

详细信息

通信作者:
郭莲怡，angel_gly@163.com

中图分类号: R575.5
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出版历程
- 收稿日期: 2021-04-22
- 录用日期: 2021-06-18
- 出版日期: 2021-12-20

Association between metabolic associated fatty liver disease and sleep disorders

Department of Gastroenterology, Postgraduate Training Base of Jinzhou Medical University & Panjin Central Hospital, Panjin, Liaoning 124000, China

Research funding:

Natural Science Foundation of Liaoning Province (JYTQN2020031)

摘要

摘要: 目的探究代谢相关脂肪性肝病(MAFLD)与睡眠障碍的关系。方法选取2020年2月—2021年2月就诊于盘锦市中心医院的MAFLD患者222例与健康者270例。将MAFLD患者根据年龄分为青年组(n=93)、中年组(n=76)、老年组(n=53);根据肝脏脂肪受控衰减参数(CAP)分为无脂肪变性组(n=23)、轻度脂肪变性组(n=85)、中度脂肪变性组(n=76)、重度脂肪变性组(n=38); 根据肝脏硬度值(LSM)分为非进展性纤维化组(n=124)、进展性纤维化组(n=98)。所有受试者均收集年龄、性别等一般资料及血常规、生化等实验室指标，并在取得知情同意前提下，分别独立完成包括匹兹堡睡眠质量指数(PSQI)量表、爱泼沃斯嗜睡量表(ESS)、慕尼黑清晨型-夜晚型问卷(MEQ)的三个睡眠量表。比较MAFLD组与健康对照组在一般资料及实验室指标上的差异，探究不同分组标准下的MAFLD与睡眠障碍的关系。计数资料2组间比较采用χ²检验。正态分布的计量资料2组间比较采用t检验; 非正态分布计量资料2组间比较采用Mann-Whitney U秩和检验。不同年龄段及不同肝脂肪变性程度的MAFLD患者组间及组内两两比较采用Kruskal-Wallis H检验。MAFLD患病的独立危险因素采用logistic回归分析。肝脂肪变性程度及肝纤维化程度与睡眠质量、嗜睡程度、昼夜节律的相关性研究采用Spearman相关分析。结果 MAFLD组在年龄、性别、患高血压、糖尿病、吸烟方面，与健康对照组相比，差异均有统计学意义(P值均＜0.05)。MAFLD组Hb、WBC、淋巴细胞百分比、ALT、AST、GGT、SUA、LDL、TBil、TC、TG、BMI均高于健康对照组，Alb、HDL均低于健康对照组(P值均＜0.05)。MAFLD患病组PSQI评分(t=35.529, P＜0.001)、ESS评分(t=24.647, P＜0.001)高于健康对照组，MEQ评分(t=-22.416, P＜0.001)、睡眠时间(t=-8.660, P＜0.001)低于健康对照组。MAFLD组组内随年龄增长、肝脂肪变性程度及肝纤维化程度升高，PSQI评分呈升高趋势，各评分因子组间两两比较，差异均有统计学意义(P值均＜0.05)。MAFLD组中绝对夜晚型、中度夜晚型、中间型高于健康对照组，中度清晨型、绝对清晨型低于健康对照组(P值均＜0.05);且随着肝脂肪变性程度及肝纤维化程度升高，MEQ评分呈降低趋势，组间两两比较，差异均有统计学意义(P值均＜0.05)。多因素logistic回归分析结果显示超重/肥胖(OR=3.166，P=0.027)、糖尿病(OR=6.811，P=0.045)、WBC升高(OR=2.301，P＜0.001)、淋巴细胞百分比升高(OR=1.316，P=0.002)、睡眠质量差(OR=8.493，P＜0.001)、嗜睡程度高(OR=5.420，P＜0.001)、昼夜节律紊乱(OR=3.805，P＜0.001)是MAFLD患病的危险因素。Spearman相关性分析显示MAFLD的肝脂肪变性程度与PSQI评分(r=0.444，P＜0.001)、ESS评分(r=0.339，P＜0.001)呈正相关，与MEQ评分(r=-0.195，P=0.004)呈负相关。肝纤维化程度与PSQI评分(r=0.518，P＜0.001)、ESS评分(r=0.373，P＜0.001)呈正相关，与MEQ评分(r=-0.250，P=0.004)呈负相关。结论与健康者相比，MAFLD患者更易发生睡眠障碍，且随着年龄、肝脂肪变性程度及肝纤维化程度升高，睡眠障碍越严重。肥胖、糖尿病、睡眠障碍是MAFLD患病的危险因素。
- 代谢相关脂肪性肝病 /
- 睡眠障碍 /
- 肝硬化
Abstract: Objective To investigate the association between metabolic associated fatty liver disease (MAFLD) and sleep disorders. Methods A total of 222 patients with MALFD who were admitted to Panjin Central Hospital from February 2020 to February 2021 and 270 healthy individuals were enrolled as subjects. According to age, the patients with MALFD were divided into youth group with 93 patients, middle-aged group with 76 patients, and elderly group with 53 patients; according to controlled attenuation parameter (CAP) of liver fat, the patients were divided into non-steatosis group with 23 patients, mild steatosis group with 85 patients, moderate steatosis group with 76 patients, and severe steatosis group with 38 patients; according to liver stiffness measurement (LSM), the patients were divided into non-progressive fibrosis group with 124 patients and progressive fibrosis group with 98 patients. Related data were collected, including general information such as age and sex and laboratory markers such as routine blood test results and biochemistry, and after informed consent was obtained, three sleep scales, i.e., Pittsburgh Sleep Quality Index (PSQI) scale, Epworth Sleepiness Scale (ESS), and Morningness-Eveningness Questionnaire (MEQ), were completed independently. The MAFLD group and the healthy control group were compared in terms of general information and laboratory markers to investigate the association between MAFLD and sleep disorders under different grouping criteria. The chi-square test was used for comparison of categorical data between two groups; the t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups; the Kruskal-Wallis H test was used for comparison between the groups of MAFLD patients with different ages and degrees of hepatic steatosis and pairwise comparison within each group. A logistic regression analysis was used to investigate the independent risk factors for MAFLD, and a Spearman correlation analysis was used to investigate the correlation of hepatic steatosis degree and fibrosis degree with sleep quality, somnolence, and circadian rhythm. Results There were significant differences in age, sex, hypertension, diabetes, and smoking between the MAFLD group and the healthy control group (all P < 0.05). Compared with the healthy control group, the MAFLD group had significantly higher hemoglobin, white blood cell count, lymphocyte percentage, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, serum uric acid, low-density lipoprotein, total bilirubin, total cholesterol, triglyceride, and body mass index and significantly lower albumin and high-density lipoprotein (all P < 0.05). Compared with the healthy control group, the MAFLD group had significantly higher PSQI score (t=35.529, P < 0.001) and ESS score (t=24.647, P < 0.001) and significantly lower MEQ score (t=-22.416, P < 0.001) and sleep time (t=-8.660, P < 0.001). With the increase in age in the MAFLD group, hepatic steatosis degree, liver fibrosis degree, and PSQI score showed an increasing trend, and pairwise comparison of each scoring factor between groups showed statistical significance (all P < 0.05). Compared with the healthy control group, the MAFLD group had a significantly higher proportion of patients with definitely evening type, moderately evening type, or intermediate type and a significantly lower proportion of patients with moderately morning type or definitely morning type (all P < 0.05), and MEQ score tended to decrease with the increase in hepatic steatosis degree and liver fibrosis degree, with significant differences between two groups (all P < 0.05). The multivariate logistic regression analysis showed that overweight/obesity (odds ratio [OR]=3.166, P=0.027), diabetes (OR=6.811, P=0.045), increase in white blood cell count (OR=2.301, P < 0.001), increase in lymphocyte percentage (OR=1.316, P=0.002), poor sleep quality (OR=8.493, P < 0.001), a high degree of somnolence (OR=5.420, P < 0.001), and circadian rhythm disturbance (OR=3.805, P < 0.001) were risk factors for MAFLD. The Spearman correlation analysis showed that in the MAFLD group, hepatic steatosis degree was positively correlated with PSQI score (r=0.444, P < 0.001) and ESS score (r=0.339, P < 0.001) and was negatively correlated with MEQ score (r=-0.195, P=0.004), and liver fibrosis degree was positively correlated with PSQI score (r=0.518, P < 0.001) and ESS score (r=0.373, P < 0.001) and was negatively correlated with MEQ score (r=-0.250, P=0.004). Conclusion Compared with healthy individuals, the patients with MAFLD often have sleep disorders, and the severity of sleep disorders increases with age, hepatic steatosis degree, and liver fibrosis degree. Obesity, diabetes, and sleep disorders are risk factors for the onset of MAFLD.
- Metabolic Associated Fatty Liver Disease /
- Dyssomnias /
- Liver Cirrhosis

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表 1 MAFLD组与健康对照组的一般资料比较

项目	MAFLD组(n=222)	健康对照组(n=270)	统计值	P值
性别[例(%)]			χ²=6.455	0.011
男	142(64.0)	142(52.6)
女	80(36.0)	128(47.4)
年龄(岁)	47.22±15.25	55.67±12.36	t=-6.791	＜0.001
BMI(kg/m²)	24.45±2.67	22.15±0.97	t=13.122	＜0.001
婚姻状况[例(%)]			χ²=1.169	0.557
未婚	29(13.1)	27(10.0)
已婚	186(83.8)	235(87.0)
离异	7(3.2)	8(3.0)
教育程度[例(%)]			χ²=7.589	0.061
小学	9(4.1)	10(3.7)
初中	30(13.5)	74(27.4)
高中	125(56.3)	143(53.0)
大学	58(26.1)	43(15.9)
长期居住地[例(%)]			χ²=3.600	0.058
农村	52(23.4)	84(31.1)
城市	170(76.6)	186(68.9)
吸烟情况[例(%)]			χ²=8.509	0.004
从不吸烟	94(42.3)	150(55.6)
现吸烟	128(57.7)	120(44.4)
高血压[例(%)]			χ²=7.230	0.007
无	144(64.9)	205(75.9)
有	78(35.1)	65(24.1)
糖尿病[例(%)]			χ²=109.307	＜0.001
无	99(44.6)	239(88.5)
有	123(55.4)	31(11.5)

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表 2 MAFLD组与健康对照组实验室指标比较

指标	MAFLD组(n=222)	健康对照组(n=270)	统计值	P值
Hb(g/L)	150.62±22.14	144.27±16.39	t=3.649	＜0.001
WBC(10⁹/L)	8.68(5.76~12.01)	5.66(4.79~6.99)	Z=-9.152	＜0.001
淋巴细胞百分比(%)	29.55(19.2~35.23)	26.75(22.48~31.10)	Z=-2.382	0.017
PLT(10⁹/L)	208.50(173.00~245.00)	202.50(173.75~243.00)	Z=-0.156	0.876
ALT(U/L)	37.50(24.00~66.25)	19.00(14.00~27.00)	Z=-10.612	＜0.001
AST(U/L)	36.00(22.00~86.25)	21.00(17.75~24.25)	Z=-10.091	＜0.001
GGT(U/L)	53.00(32.00~121.00)	21.00(15.00~32.00)	Z=-12.231	＜0.001
IBil(μmol/L)	9.50(6.93~12.87)	9.27(6.94~12.47)	Z=-0.833	0.405
TBil(μmol/L)	14.39(10.80~20.25)	12.12(9.63~16.21)	Z=-3.752	＜0.001
Alb(g/L)	41.04±7.74	44.95±3.31	t=-7.512	＜0.001
SUA(μmol/L)	368.50(302.75~448.50)	311.00(258.75~387.50)	Z=-5.840	＜0.001
LDL(mmol/L)	3.42(2.56~4.44)	2.79(2.42~3.25)	Z=-5.972	＜0.001
HDL(mmol/L)	1.11(0.95~1.38)	1.33(1.16~1.47)	Z=-6.286	＜0.001
TC(mmol/L)	5.53(4.68~8.10)	4.86(4.31~5.45)	Z=-7.104	＜0.001
TG(mmol/L)	3.68(1.91~14.51)	1.34(0.98~1.83)	Z=-13.775	＜0.001

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表 3 MAFLD组与健康对照组睡眠量表评分比较

项目	MAFLD组(n=222)	健康对照组(n=270)	统计值	P值
睡眠时间(h)	6.78±0.69	7.27±0.59	t=-8.660	＜0.001
PSQI评分	11.52±3.10	4.10±1.35	t=35.529	＜0.001
ESS评分	6.98±1.94	3.43±1.23	t=24.647	＜0.001
MEQ评分	47.28±11.84	65.93±6.20	t=-22.416	＜0.001
绝对夜晚型[例(%)]	9(4.1)	0	χ²=9.007	0.003
中度夜晚型[例(%)]	75(33.8)	2(0.7)	χ²=100.763	＜0.001
中间型[例(%)]	94(42.3)	19(7.0)	χ²=85.831	＜0.001
中度清晨型[例(%)]	40(18.0)	185(68.5)	χ²=125.193	＜0.001
绝对清晨型[例(%)]	4(1.8)	64(23.7)	χ²=49.065	＜0.001

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表 4 MAFLD组内不同年龄组的PSQI评分及因子分比较

组别	PSQI评分	睡眠时间因子	睡眠效率因子	睡眠障碍因子	催眠药物因子	日间功能障碍因子	睡眠质量因子	入睡时间因子
青年(n=93)	10.41±3.28	1.09±0.29	1.70±0.72	1.67±0.70	1.13±0.34	1.53±0.72	1.85±0.71	1.72±0.70
中年(n=76)	11.26±2.28¹⁾	1.11±0.31	1.84±0.67¹⁾	1.79±0.62¹⁾	1.17±0.38¹⁾	1.71±0.65¹⁾	1.98±0.71¹⁾	1.77±0.71¹⁾
老年(n=53)	13.83±2.52¹⁾²⁾	1.15±0.36	2.34±0.52¹⁾²⁾	2.23±0.70¹⁾²⁾	1.49±0.54¹⁾²⁾	1.94±0.74¹⁾²⁾	1.99±0.68¹⁾²⁾	1.81±0.68¹⁾²⁾
H值	40.368	1.118	29.496	21.463	23.386	11.981	33.355	36.188
P值	＜0.001	0.572	＜0.001	＜0.001	＜0.001	0.003	＜0.001	＜0.001
注：与青年组比较，1)P＜0.05;与中年组比较，2)P＜0.05。

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表 5 MAFLD组内不同肝脂肪变性程度的MEQ评分、PSQI评分及因子分比较

组别	PSQI评分	睡眠时间因子	睡眠效率因子	睡眠障碍因子	催眠药物因子	日间功能障碍因子	睡眠质量因子	入睡时间因子	MEQ评分
无脂肪变性(n=23)	10.43±2.62	1.08±0.28	1.65±0.57	1.61±0.72	1.09±0.39	1.45±0.61	1.80±0.73	1.57±0.72	52.08±11.20
轻度脂肪变性(n=85)	10.55±2.31¹⁾	1.09±0.27	1.82±0.65¹⁾	1.65±0.59¹⁾	1.17±0.29¹⁾	1.48±0.51¹⁾	1.84±0.65¹⁾	1.62±0.61¹⁾	48.70±11.60¹⁾
中度脂肪变性(n=76)	11.22±3.12¹⁾²⁾	1.12±0.32	1.75±0.71¹⁾²⁾	1.84±0.71¹⁾²⁾	1.26±0.44¹⁾²⁾	1.67±0.68¹⁾²⁾	1.91±0.67¹⁾²⁾	1.74±0.68¹⁾²⁾	46.96±11.82¹⁾²⁾
重度脂肪变性(n=38)	14.92±2.53¹⁾²⁾³⁾	1.18±0.39	2.53±0.51¹⁾²⁾³⁾	2.42±0.59¹⁾²⁾³⁾	1.53±0.55¹⁾²⁾³⁾	2.39±0.67¹⁾²⁾³⁾	2.55±0.55¹⁾²⁾³⁾	2.32±0.57¹⁾²⁾³⁾	42.04±11.54¹⁾²⁾³⁾
H值	50.173	2.892	36.587	33.389	25.731	43.266	33.826	29.323	11.889
P值	＜0.001	0.409	＜0.001	＜0.001	＜0.001	＜0.001	＜0.001	＜0.001	0.008
注：与无脂肪变性组比较，1)P＜0.05;与轻度脂肪变性组比较，2)P＜0.05;与中度脂肪变性组比较，3)P＜0.05。

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表 6 MAFLD组内不同肝纤维化程度的MEQ评分、PSQI评分及因子分比较

组别	PSQI评分	睡眠时间因子	睡眠效率因子	睡眠障碍因子	催眠药物因子	日间功能障碍因子	睡眠质量因子	入睡时间因子	MEQ评分
非进展组(n=124)	10.24±2.36	1.07±0.26	1.71±0.64	1.61±0.61	1.10±0.29	1.41±0.57	1.77±0.65	1.56±0.64	49.78±11.42
进展组(n=98)	13.13±3.16	1.16±0.37	2.14±0.70	2.13±0.71	1.41±0.51	2.04±0.73	2.19±0.69	2.05±0.64	44.10±11.65
t值	-7.786	-2.135	-4.764	-5.861	-5.655	-7.208	-4.705	-5.678	3.647
P值	＜0.001	0.034	＜0.001	＜0.001	＜0.001	＜0.001	＜0.001	＜0.001	＜0.001

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表 7 MAFLD患病影响因素Logistic回归分析

项目	回归系数	标准误	Wald	OR(95%CI)	P值
年龄	-0.013	0.047	4.071	0.987(0.900~1.084)	0.039
性别(女)	0.003	1.414	0.000	1.003(0.063~16.042)	0.998
BMI(超重/肥胖)	1.153	0.522	4.868	3.166(1.137~8.815)	0.027
高血压	0.739	1.100	0.451	2.093(0.242~16.042)	0.502
糖尿病	1.918	0.956	4.025	6.811(1.045~44.378)	0.045
吸烟情况	-1.251	1.508	0.688	0.286(0.015~5.497)	0.407
WBC	0.833	0.236	12.49	2.301(1.449~3.653)	＜0.001
淋巴细胞百分比	0.275	0.088	9.667	1.316(1.107~1.565)	0.002
HDL	-10.098	3.209	9.905	0.000(0.000~0.022)	0.002
睡眠时间	-1.296	0.725	3.193	0.274(0.066~1.134)	0.044
ESS评分	1.690	0.441	14.667	5.420(2.282~12.870)	＜0.001
MEQ评分	2.773	0.515	28.941	3.805(1.607~5.862)	＜0.001
PSQI评分	2.139	0.302	50.098	8.493(4.697~15.357)	＜0.001

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