A preliminary study on sleep disorders and related risk factors in patients with liver cirrhosis
肝硬化患者睡眠障碍及相关危险因素的初步研究

摘要

目的 本研究旨在对肝硬化患者的睡眠障碍进行初步的研究和分析，并探讨肝硬化患者发生睡眠障碍的危险因素，以期提高肝硬化患者合并睡眠障碍的生存质量，尽早预防肝硬化患者发生睡眠障碍。方法 本研究选取2024年10月至2025年6月期间于大理大学第二附属医院住院的172例肝硬化患者作为研究对象，同时选择同期48例健康体检人群作为健康对照组。（1）采用匹兹堡睡眠质量指数量表（pittsburgh sleep quality index, PSQI）对入组的肝硬化患者和健康对照组的睡眠情况进行评估，分析肝硬化患者合并睡眠障碍的发病情况。（2）依据PSQI评分将172例肝硬化患者分为无睡眠障碍组、轻度睡眠障碍组、中度睡眠障碍组和重度睡眠障碍组。对四组的一般资料包括年龄、性别、吸烟史、饮酒史和疾病资料包括肝硬化病因、Child-Pugh分级、慢性病史≥5种、长期用药史、身体质量指数（body mass index, BMI）进行分析，分析肝硬化患者合并睡眠障碍的影响因素。（3）依据PSQI评分将172例肝硬化患者分为无睡眠障碍组、轻度睡眠障碍组、中度睡眠障碍组和重度睡眠障碍组。对四组的实验室资料包括白细胞计数（white blood cell, WBC）、红细胞计数（red blood cell, RBC）、血红蛋白（hemoglobin, HGB）、红细胞比容（hematocrit value, HCT）、血小板计数（platelets, PLT）、C-反应蛋白（C-reactive protein, CRP）、降钙素原（procalcitonin, PCT）、凝血酶原时间（prothrombin Time, PT）、凝血酶原活动度（prothrombin Activity, PTA）、抗凝血酶Ⅲ、丙氨酸氨基转移酶（alanine aminotransferase, ALT）、天冬氨酸氨基转移酶（aspartate Transaminase, AST）、总胆红素（total bilirubin, TBIL）、直接胆红素（direct bilirubin, DBIL）、间接胆红素（indirect bilirubin, IBIL）、人血清白蛋白（albumin, ALB）、尿素、尿酸、肌酸激酶、同型半胱氨酸、血清钾离子（kalium, K+）、血清钠离子（natrium, Na+）、血清氯离子（chlorine, CL-）、血清钙离子（calcium, Ca2+）、血清镁离子（magnesium, Mg2+）、血清磷离子（phosphor, Pi）、乳酸、甘油三酯（triglyceride, TG）、总胆固醇（total cholesterol, TC）、高密度脂蛋白（high-density lipoprotein cholesterol，HDL）、低密度脂蛋白胆固醇（low-density lipoprotein cholesterol, LDL）、血氨、糖类抗原125（carbohydrate antigen 125, CA125）、糖类抗原153（carbohydrate antigen 153, CA153）、糖类抗原199（carbohydrate antigen 199, CA199）、癌胚抗原（carcinoma embryonic antigen, CEA）、甲胎蛋白（alpha-fetoprotein, AFP）和影像学资料（门静脉内径、脾静脉内径、脾脏厚度）进行分析，分析肝硬化患者合并睡眠障碍的影响因素。（4）依据PSQI评分将172例肝硬化患者分为无睡眠障碍组、轻度睡眠障碍组、中度睡眠障碍组和重度睡眠障碍组。对四组的一般资料、疾病资料、实验室指标和影像学指标中影响睡眠具有统计学意义的指标进行单因素Logistic回归分析，分析肝硬化患者睡眠障碍的影响因素，再通过多因素Logistic回归分析筛选肝硬化患者睡眠障碍的独立危险因素。结果 （1）肝硬化患者的PSQI评分显著高于健康对照组，两组在发生睡眠障碍上存在统计学差异。肝硬化患者较健康对照组更易发生睡眠障碍。（2）肝硬化患者不同睡眠障碍组间一般资料比较，四组间在年龄、性别、吸烟史、饮酒史上均无统计学差异（P＞0.05）。（3）肝硬化患者不同睡眠障碍组之间进行疾病资料统计学分析，四组间在Child-Pugh分级上存在统计学差异（P＜0.001）；而四组间在肝硬化病因、慢性病史≥5种、长期用药史、BMI均无统计学差异（P＞0.05）。（4）肝硬化患者不同睡眠障碍组之间进行实验室指标进行比较，四组间在CRP、PT、PTA、TBIL、DBIL、ALB、Na+、TC、LDL、血氨上均存在统计学差异（P＜0.05）；而四组间在WBC、RBC、HGB、HCT、PLT、PCT、抗凝血酶III、ALT、AST、IBIL、尿素、尿酸、肌酸激酶、同型半胱氨酸、K+、CL-、Ca2+、Mg2+、P、乳酸、TG、HDL、CA125、CA153、CA199、CEA、AFP上均无统计学差异（P＞0.05）。（5）肝硬化患者不同睡眠障碍组之间的影像学指标进行比较，结果显示：四组间在门静脉内径、脾静脉内径、脾脏厚度上均存在统计学差异（P＜0.05）。（6）肝硬化患者四组不同睡眠障碍组之间进行单因素分析，结果显示血氨、门静脉内径、脾脏厚度在不同睡眠障碍组之间两两比较差异均具有统计学意义（P＜0.05），是肝硬化患者发生睡眠障碍的危险因素。（7）多因素分析结果显示：血氨、门静脉内径在不同睡眠障碍组之间两两比较差异均具有统计学意义（P＜0.05）。以重度睡眠障碍组血氨水平为参照，无睡眠障碍组、轻度睡眠障碍组及中度睡眠障碍组患者发生睡眠障碍的风险分别降低 7.7%、4.4%和3.3%（无睡眠障碍组：OR=0.923，95%CI：0.892~0.955，P<0.001；轻度睡眠障碍组：OR=0.956，95%CI：0.933~0.979，P<0.001；中度睡眠障碍组：OR=0.967，95%CI：0.946~0.988，P=0.003）。以重度睡眠障碍组门静脉内径值为参照，无睡眠障碍组（OR=0.528，95% CI：0.419~0.665，P<0.001）、轻度睡眠障碍组（OR=0.645，95% CI：0.539~0.770，P<0.001）及中度睡眠障碍组（OR=0.770，95% CI：0.667~0.889，P<0.001）患者发生睡眠障碍的风险分别降低 47.2%、35.5%和23.0%。血氨水平升高、门静脉内径增宽是肝硬化患者发生睡眠障碍的独立危险因素。结论 （1）肝硬化患者睡眠障碍的发生率显著高于健康人群。（2）血氨、门静脉内径、脾脏厚度是肝硬化患者发生睡眠障碍的危险因素。（3）血氨水平增加、门静脉内径增宽是肝硬化患者发生睡眠障碍的独立危险因素。

Abstract

Objective This study aims to conduct a preliminary investigation and analysis of sleep disorders in patients with liver cirrhosis and explore the risk factors associated with the occurrence of sleep disorders in this patient population, with the goal of improving the quality of life for cirrhotic patients with comorbid sleep disturbances and facilitating early prevention of such disorders.
Methods A total of 172 cirrhotic patients hospitalized at the Second Affiliated Hospital of Dali University between October 2024 and June 2025 were enrolled as the study cohort, along with 48 healthy individuals undergoing routine health examinations during the same period serving as the control group.(1) The Pittsburgh Sleep Quality Index (PSQI) was utilized to assess sleep quality in both the cirrhotic patient group and the healthy control group, enabling analysis of the incidence of sleep disorders among cirrhotic patients.(2) Based on PSQI scores, the 172 cirrhotic patients were categorized into four groups: no sleep disorder, mild sleep disorder, moderate sleep disorder, and severe sleep disorder. Demographic characteristics (including age, gender, smoking history, and alcohol consumption history) and disease-related parameters (including etiology of cirrhosis, Child-Pugh classification, history of chronic diseases ≥5, long-term medication use, and body mass index [BMI]) were compared across the four groups to identify factors influencing sleep disorders in cirrhotic patients.(3) Laboratory parameters were analyzed across the four groups, including white blood cell count (WBC), red blood cell count (RBC), hemoglobin (HGB), hematocrit (HCT), platelet count (PLT), C-reactive protein (CRP), procalcitonin (PCT), prothrombin time (PT), prothrombin activity (PTA), antithrombin III, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), albumin (ALB), urea, uric acid, creatine kinase, homocysteine, serum potassium (K⁺), sodium (Na⁺), chloride (Cl⁻), calcium (Ca²⁺), magnesium (Mg²⁺), phosphorus (P), lactate, triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), blood ammonia, carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153), carbohydrate antigen 199 (CA199), carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), as well as imaging parameters (portal vein diameter, splenic vein diameter, and spleen thickness), to determine their association with sleep disorders in cirrhotic patients.(4) Univariate logistic regression analysis was performed on demographic, clinical, laboratory, and imaging parameters that demonstrated statistical significance in influencing sleep disorders among the four groups. Multivariate logistic regression was subsequently conducted to identify independent risk factors for sleep disorders in cirrhotic patients.
Results (1) PSQI scores were significantly higher in cirrhotic patients compared to the healthy control group, with a statistically significant difference in the prevalence of sleep disorders between the two groups. Cirrhotic patients were more prone to sleep disorders than healthy individuals. (2) No statistically significant differences were observed among the four sleep disorder groups in terms of age, gender, smoking history, or alcohol consumption history (P > 0.05). (3) Analysis of disease-related parameters revealed a statistically significant difference in Child-Pugh classification among the four groups (P < 0.001). However, no significant differences were found in cirrhosis etiology, history of chronic diseases ≥5, long-term medication use, or BMI (P > 0.05). (4) Comparison of laboratory indicators showed statistically significant differences among the four groups in CRP, PT, PTA, TBIL, DBIL, ALB, Na⁺, TC, LDL, and blood ammonia (P < 0.05). In contrast, no significant differences were observed in WBC, RBC, HGB, HCT, PLT, PCT, antithrombin III, ALT, AST, IBIL, urea, uric acid, creatine kinase, homocysteine, K⁺, Cl⁻, Ca²⁺, Mg²⁺, P, lactate, TG, HDL, CA125, CA153, CA199, CEA, or AFP (P > 0.05). (5) Statistically significant differences were identified among the four groups in imaging parameters, including portal vein diameter, splenic vein diameter, and spleen thickness (P < 0.05). (6) Univariate analysis indicated that blood ammonia, portal vein diameter, and spleen thickness were significantly different in pairwise comparisons among the sleep disorder groups (P < 0.05), identifying them as risk factors for sleep disorders in cirrhotic patients. (7) Multivariate analysis showed that there were statistically significant differences in blood ammonia and portal vein diameter between different groups of sleep disorders (P < 0.05). Compared with the severe sleep disorder group used as the reference, the risk of sleep disorders was reduced by 7.7%, 4.4%, and 3.3% in the non-sleep disorder group, mild sleep disorder group, and moderate sleep disorder group, respectively (non-sleep disorder group: OR=0.923, 95%CI: 0.892–0.955, P<0.001; mild sleep disorder group: OR=0.956, 95%CI: 0.933–0.979, P<0.001; moderate sleep disorder group: OR=0.967, 95%CI: 0.946–0.988, P=0.003). Similarly, compared with the severe sleep disorder group, the risk of sleep disorders was decreased by 47.2%, 35.5%, and 23.0% in the non-sleep disorder group (OR=0.528, 95%CI: 0.419–0.665, P<0.001), mild sleep disorder group (OR=0.645, 95%CI: 0.539–0.770, P<0.001), and moderate sleep disorder group (OR=0.770, 95%CI: 0.667–0.889, P<0.001), respectively. Elevated blood ammonia and increased portal vein diameter were independent risk factors for sleep disorders in patients with liver cirrhosis.
Conclusion   (1) The incidence of sleep disorders is significantly higher in cirrhotic patients compared to the healthy population. (2) Blood ammonia, portal vein diameter, and spleen thickness are identified as risk factors for sleep disorders in cirrhotic patients. (3) Elevated blood ammonia and increased portal vein diameter are independent risk factors for sleep disturbance in patients with liver cirrhosis.