精神分裂症患者长期服用第二代抗精神病药物导致肝损伤的影响因素分析

申变红; 汪程鹏; 高可润; 张开元; 张智雯; 朱春燕; 方玲; 汤剑平

doi:10.16766/j.cnki.issn.1674-4152.003203

精神分裂症患者长期服用第二代抗精神病药物导致肝损伤的影响因素分析

doi: 10.16766/j.cnki.issn.1674-4152.003203

杭州市第七人民医院(浙江大学医学院附属精神卫生中心)精神科, 浙江杭州 310013

基金项目:

浙江省医药卫生科技计划项目 2021RC025

浙江省医药卫生科技计划项目 2019RC073

详细信息

通讯作者:
申变红，E-mail: shenbianhong1982@163.com

中图分类号: R749.3 R971.41
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出版历程
- 收稿日期: 2023-05-26
- 网络出版日期: 2023-11-23

Analysis of factors influencing liver injury caused by long-term use of second-generation antipsychotics in patients with schizophrenia

Department of Psychiatry, Hangzhou Seventh People's Hospital (Affiliated Mental Health Center of Zhejiang University School of Medicine), Hangzhou, Zhejiang 310013, China

摘要

摘要: 目的通过回顾性研究，探讨精神分裂症患者长期服用帕利哌酮、齐拉西酮等第二代抗精神病药物相关肝功能受损的危险因素。方法选择2021年4月—2023年4月杭州市第七人民医院收治的长期服用第二代抗精神病药物的120例精神分裂症患者进行回顾性研究，根据是否发生肝损伤将其分为2组，36例发生肝损伤的患者为观察组，84例未发生肝损伤的患者为对照组，采用单因素、多因素logistic回归分析研究肝损伤的危险因素。结合logistic回归分析结果，通过R软件构建预测精神分裂症患者长期服用第二代抗精神病药物导致肝损伤的列线图预测模型，绘制受试者工作曲线(ROC)，计算曲线下面积(AUC)，分析该模型的预测区分度。结果 Logistic回归分析显示，病程>10年、肝病史、饮酒史、营养不良、结核病、抗精神病药物服用种类≥3种是精神分裂症患者长期服用第二代抗精神病药物导致肝损伤的危险因素(均P＜0.05)。Hosmer-Lemeshow拟合优度检验，χ²=3.049，P=0.405；C-index=0.910；AUC为0.910(95% CI：0.804~0.946)。结论精神分裂症患者长期服用第二代抗精神病药物引发肝损伤的影响因素是病程，危险因素包括肝病史、饮酒史、营养不良、结核病、抗精神病药物服用种类≥3种，构建预测模型的预测效能较高。
- 精神分裂症 /
- 抗精神病药物 /
- 肝损伤 /
- 影响因素
Abstract: Objective A retrospective study was conducted to investigate the risk factors for liver dysfunction associated with long-term use of paliperidone, ziprasidone and other second-generation antipsychotics in patients with schizophrenia. Methods A retrospective study was conducted on 120 patients with schizophrenia who were on long-term second-generation antipsychotics in Hangzhou Seventh People's Hospital from April 2021 to April 2023. They were divided into 2 groups according to whether they had liver injury or not. Thirty-six patients with liver injury were set as the observation group, and 84 patients without liver injury were set as the control group. The risk factors of liver injury were investigated by univariate and multivariate logistic regression analysis. Combined with the results of logistic regression analysis results, R software was used to build a nomogram prediction model for predicting liver injury caused by long-term use of second-generation antipsychotics in schizophrenia patients, and the receiver operating curve (ROC) was plotted, the area under the curve (AUC) was calculated, and the predictive ability of this model was analyzed. Results Logistic regression analysis showed that disease duration >10 years, history of liver disease, history of alcohol consumption, malnutrition, tuberculosis and type of antipsychotic drugs ≥3 were risk factors for long-term use of second-generation antipsychotics in schizophrenia patients (P < 0.05). Hosmer-Lemeshow goodness of fit test, χ²=3.049, P=0.405; C-index=0.910; AUC was 0.910 (95% CI: 0.804-0.946). Conclusion Influencing factors for liver injury induced by long-term use of second-generation antipsychotics in schizophrenia patients were disease duration, and risk factors included liver disease history, alcohol consumption, malnutrition, tuberculosis and type of antipsychotics ≥3 types. The prediction model had a high predictive power.
- Schizophrenia /
- Antipsychotic drugs /
- Liver injury /
- Influencing factor

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图 1 预测精神分裂症患者长期服用第二代抗精神病药物引发肝损伤的列线图模型

Figure 1. The nomographic model for predicting liver injury induced by long-term use of second-generation antipsychotic drugs in patients with schizophrenia

下载: 全尺寸图片幻灯片

图 2 预测精神分裂症患者长期服用第二代抗精神病药物引发肝损伤的校准曲线

Figure 2. Calibration curve for predicting liver injury induced by long-term use of second-generation antipsychotic drugs in patients with schizophrenia

下载: 全尺寸图片幻灯片

图 3 预测精神分裂症患者长期服用第二代抗精神病药物引发肝损伤的ROC曲线

Figure 3. ROC curve for predicting liver injury induced by long-term use of second-generation antipsychotic drugs in patients with schizophrenia

下载: 全尺寸图片幻灯片

表 1 精神分裂症患者长期服用第二代抗精神病药物引发肝损伤的单因素分析[例(%)]

Table 1. Univariate analysis of liver injury induced by long-term use of second-generation antipsychotics in patients with schizophrenia[case(%)]

项目	类别	观察组(n=36)	对照组(n=84)	统计量	P值	项目	类别	观察组(n=36)	对照组(n=84)	统计量	P值
性别	男性	17(47.22)	40(47.62)	0.002^a	0.968	吸烟史	有	25(69.44)	61(72.62)	0.125^a	0.724
	女性	19(52.78)	44(52.38)				无	11(30.56)	23(27.38)
年龄	< 45岁	18(50.00)	48(57.14)	0.520^a	0.471	肝病史	有	16(44.44)	9(10.71)	17.384^a	< 0.001
	≥45岁	18(50.00)	36(42.86)				无	20(55.56)	75(89.29)
病程	< 5年	2(5.56)	22(26.19)	3.422^b	0.001	饮酒史	有	26(72.22)	39(46.43)	6.753^a	0.009
	5~10年	13(36.11)	38(45.24)				无	10(27.78)	45(53.57)
	>10年	21(58.33)	24(28.57)			营养不良	有	28(77.78)	41(48.81)	8.653^a	0.003
BMI	< 18.5	16(44.44)	40(47.62)	0.976^b	0.329		无	8(22.22)	43(51.19)
	18.5~24.0	11(30.56)	35(41.67)			贫血	有	17(47.22)	34(40.48)	0.469^a	0.493
	>24.0	9(25.00)	9(10.71)				无	19(52.78)	50(59.52)
诊断分型	单纯型	15(41.67)	36(42.86)	0.015^a	0.904	心功能不全	有	12(33.33)	32(38.10)	0.246^a	0.620
	偏执型	21(58.33)	48(57.14)				无	24(66.67)	52(61.90)
家族遗传史	有	29(80.56)	70(83.33)	0.135^a	0.714	结核病	有	13(36.11)	6(7.14)	15.868^a	< 0.001
	无	7(19.44)	14(16.67)				无	23(63.89)	78(92.86)
糖尿病	有	8(22.22)	24(28.57)	0.520^a	0.471	抗精神病药物服用种类	1种	4(11.11)	25(29.76)	3.598^b	0.001
	无	28(77.78)	60(71.43)				2种	15(41.67)	46(54.76)
高血压	有	7(19.44)	20(23.81)	0.275^a	0.600		≥3种	17(47.22)	13(15.48)
	无	29(80.56)	64(76.19)
注：^a为χ²值，^b为Z值。

下载: 导出CSV

表 2 长期服用第二代抗精神病药物引发肝损伤的危险因素变量赋值情况

Table 2. Assignment of risk factor variables for liver injury induced by long-term use of second-generation antipsychotic medications

变量	赋值方法
病程	< 5年=0，5~10年=1，>10年=2
肝病史	无=0，有=1
饮酒史	无=0，有=1
营养不良	无=0，有=1
结核病	无=0，有=1
抗精神病药物服用种类	1种=0，2种=1，≥3种=2

下载: 导出CSV

表 3 精神分裂症患者长期服用第二代抗精神病药物引发肝损伤的多因素分析

Table 3. Multivariable analysis of liver injury induced by long-term use of second-generation antipsychotic medications in patients with schizophrenia

因素	B	SE	Wald χ²	P值	OR值	95%CI
病程>10年	0.216	0.075	8.158	< 0.001	1.224	1.101~1.418
肝病史	0.286	0.077	13.794	< 0.001	1.329	1.146~1.511
饮酒史	0.180	0.061	7.019	< 0.001	1.164	0.986~1.207
营养不良	0.198	0.061	9.518	< 0.001	1.206	1.038~1.328
结核病	0.234	0.059	15.758	< 0.001	1.286	1.135~1.482
抗精神病药物服用种类≥3种	0.231	0.072	10.284	< 0.001	1.256	1.113~1.462

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