老年药物性肝衰竭65例临床特征分析

王丽苹; 何婷婷; 崔延飞; 王仲霞; 朱云; 景婧; 孙永强; 许文涛; 余思邈; 桑秀秀; 田淼; 王立福; 王睿林

doi:10.3969/j.issn.1001-5256.2021.07.029

老年药物性肝衰竭65例临床特征分析

DOI: 10.3969/j.issn.1001-5256.2021.07.029

1.
解放军总医院第五医学中心中医肝病科，北京 100039
2.
河南中医药大学第一附属医院脾胃肝胆科，郑州 450000

基金项目:

国家自然科学基金 (81673806);

中国医药教育协会2020重大科学攻关问题和医药技术难题科研课题 (2020KTY001)

利益冲突声明： 本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：王丽苹、何婷婷负责提出研究选题，实施研究过程，起草论文，修订论文，终审论文；崔延飞、王仲霞、朱云、景婧负责统计分析，设计论文框架；孙永强、许文涛、余思邈、桑秀秀、田淼、王立福负责调研整理文献，采集整理分析数据；王睿林负责设计研究方案，技术或材料支持，指导性支持。

详细信息

通信作者:
王睿林，wrl7905@163.com

中图分类号: R575.3
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出版历程
- 收稿日期: 2020-10-06
- 录用日期: 2021-01-15
- 出版日期: 2021-07-20

Clinical features of elderly patients with drug-induced liver failure: An analysis of 65 cases

1.
Department of Hepatology of Traditional Chinese Medicine, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China
2.
Department of Hepatology and Spleen-Stomach, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, China

摘要

摘要: 目的了解老年药物性肝衰竭(DILF)的疾病特征及用药情况，为临床防治老年DILF提供参考。方法选取2015年1月—2019年12月于解放军总医院第五医学中心明确诊断为DILF且年龄≥60岁的患者65例，按临床疗效判定标准进行分组，治愈和好转为治疗有效组，无效和死亡为治疗无效组。统计分析老年DILF患者的年龄、性别、基础疾病、用药种类、临床分型、并发症及预后等临床资料。计量资料两组间比较采用t检验或Mann-Whitney U检验；计数资料两组间比较采用χ²检验或Fisher精确检验。结果 65例老年DILF患者中，男17例(26.2%)，女48例(73.8%)，男女比例1∶ 2.82，老年DILF分型以亚急性肝衰竭为主(81.5%)，临床分型以胆汁淤积型多见(40%)。治疗有效组共26例(40%)，治疗无效组共39例(60%)。在并发症方面，治疗有效组胸腹水比例高于无效组(61.5% vs 28.2%)，肝肾综合征比例低于无效组(19.2% vs 56.4%)，未合并肝性脑病比例高于无效组(80.8% vs 30.8%)，合并肝性脑病4期比例低于无效组(0 vs 20.5%)，差异均有统计学意义(χ²值分别为7.138、8.880、15.604，P值均＜0.05)。引起DILF的主要药物包括：化学类以心脑血管药物(10.8%)为主，其次是降压药(9.2%)和抗生素(7.7%)；中药类主要为中成药(35.4%)和中草药(23.1%)；生物制剂中以保健品多见(20.0%)。结论老年DILF以亚急性肝衰竭多见，临床分型以胆汁淤积型为主，并发肝性脑病及肝肾综合征易导致预后不佳。
- 化学性与药物性肝损伤 /
- 肝功能衰竭 /
- 体征和症状
Abstract: Objective To investigate the features and medication of elderly patients with drug-induced liver failure (DILF), and to provide a reference for clinical prevention and treatment of DILF in elderly patients. Methods A total of 65 elderly patients, aged ≥60 years, who were diagnosed with DILF in The Fifth Medical Center of Chinese PLA General Hospital from January 2015 to December 2019 were enrolled and divided into groups based on the criteria for clinical outcome evaluation. The patients who were cured or improved were enrolled as response group, and those who had no response or died were enrolled as non-response group. Related clinical data were collected and analyzed, including age, sex, underlying diseases, type of the drug used, clinical classification, complications, and prognosis. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results Among the 65 elderly patients with DILF, there were 17 male patients (26.2%) and 48 female patients (73.8%), with a male/female ratio of 1∶ 2.82. Subacute liver failure (SALF) was the main type of DILF in the elderly patients (81.5%), and cholestasis type was the most common clinical type (40%). There were 26 patients in the response group and 39 in the non-response group, accounting for 40% and 60%, respectively, of all patients. As for complications, compared with the non-response group, the response group had a significantly higher proportion of patients with pleuroperitoneal fluid (61.5% vs 28.2%, P < 0.05), a significantly lower proportion of patients with hepatorenal syndrome (19.2% vs 56.4%, P < 0.05), a significantly higher proportion of patients without hepatic encephalopathy (80.8% vs 30.8%, P < 0.05), and a significantly lower proportion of patients with stage 4 hepatic encephalopathy (0 vs 20.5%, P < 0.05). The main drugs causing DILF included cardiovascular and cerebrovascular drugs (10.8%), antihypertensive drugs (9.2%), and antibiotics (7.7%); traditional Chinese medicine drugs were mainly Chinese patent drugs (35.4%) and Chinese herbal medicine (23.1%); healthcare product was the most common type of biological products (20.0%). Conclusion SALF is the most common type of DILF in the elderly, and cholestasis type is the main clinical type of DILF. Patients with hepatic encephalopathy and hepatorenal syndrome tend to have poor prognosis.
- Chemical and Drug Induced Liver Injury /
- Liver Failure /
- Signs and Symptoms

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表 1 65例DILF患者实验室指标

项目	ALF组(n=12)	SALF组(n=53)	统计值	P值
男/女(例)	4/8	13/40	χ²=0.069	0.717
年龄(岁)	66.50(61.50~73.75)	66.00(63.00~68.50)	Z=-0.415	0.678
Alb(g/L)	29.08±5.20	26.36±4.37	t=1.183	0.064
TBil(μmol/L)	285.94±192.00	313.65±141.67	t=-0.572	0.570
ALT(U/L)	98.50(36.75~155.75)	142.00(41.50~334.50)	Z=0.888	0.375
AST(U/L)	101.50(54.25~174.25)	174.00(103.50~468.50)	Z=2.198	0.028
GGT(U/L)	100.00(37.75~179.25)	59.00(35.00~90.50)	Z=-1.319	0.187
ChE(U/L)	2 728.00(1 269.00~3 375.00)	2 012.00(1 464.00~3 335.50)	Z=-0.406	0.685
LDH(U/L)	248.00(184.50~300.25)	268.00(224.00~366.00)	Z=1.505	0.132
BUN(mmol/L)	5.60(3.48~20.18)	8.50(3.85~16.60)	Z=0.457	0.648
Scr(μmol/L)	81.00(61.50~107.75)	103.00(76.00~173.00)	Z=1.285	0.199
UA(μmol/L)	159.00(128.25~303.50)	201.00(112.00~325.50)	Z=0.600	0.548
PTA(%)	48.95(39.90~66.75)	29.80(25.05~35.65)	Z=-5.377	＜0.001
INR	1.46(1.27~1.62)	1.94(1.75~2.29)	Z=4.465	＜0.001
血氨(μmol/L)	50.00(25.00~77.00)	50.00(37.00~92.50)	Z=0.739	0.460
注：LDH，乳酸脱氢酶；UA，尿酸。

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表 2 65例DILF患者临床分型及并发症比较

项目	治疗有效组(n=26)	治疗无效组(n=39)	统计值	P值
年龄(岁)	67.12±5.03	66.90±6.13	t=0.150	0.881
性别[例(%)]			χ²=3.399	0.065
男	10(38.5)	7(17.9)
女	16(61.5)	32(82.1)
临床分型[例(%)]
胆汁淤积型	11(42.3)	15(38.5)	χ²=0.096	0.756
肝细胞损伤型	7(26.9)	15(38.5)	χ²=0.928	0.335
混合型	8(30.8)	9(23.1)	χ²=0.478	0.489
无胸腹水[例(%)]	2(7.7)	5(12.8)		0.693
胸腹水[例(%)]	16(61.5)	11(28.2)	χ²=7.138	0.011
单纯胸水[例(%)]	8(30.8)	20(51.3)	χ²=2.677	0.102
单纯腹水[例(%)]	0	3(7.7)		0.269
电解质紊乱[例(%)]	21(80.8)	36(92.3)		0.250
消化道出血[例(%)]	2(7.7)	8(20.5)		0.293
肝肾综合征[例(%)]	5(19.2)	22(56.4)	χ²=8.880	0.003
感染[例(%)]
肺部感染	10(38.5)	18(46.2)	χ²=0.376	0.540
腹膜炎	7(26.9)	16(41.0)	χ²=1.357	0.244
泌尿系感染	2(7.7)	2(5.1)		1.000
口腔感染	2(7.7)	4(10.3)		1.000
HE[例(%)]
无HE	21(80.8)	12(30.8)	χ²=15.604	＜0.001
HE 1期	4(15.4)	11(28.2)	χ²=1.444	0.229
HE 2期	1(3.8)	3(7.7)		0.644
HE 3期	0	5(12.8)		0.078
HE 4期	0	8(20.5)		0.018

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表 3 65例DILF患者基础疾病情况

项目	所有患者	治疗有效组(n=26)	治疗无效组(n=39)	P值
高血压病[例(%)]	15(23.1)	5(19.2)	10(25.6)	0.548
冠心病[例(%)]	9(13.8)	2(7.7)	7(17.9)	0.420
糖尿病[例(%)]	11(16.9)	6(23.1)	5(12.8)	0.458
脑梗塞[例(%)]	7(10.8)	3(11.5)	4(10.3)	1.000
肿瘤[例(%)]	9(13.8)	3(11.5)	6(15.4)	0.731
慢性阻塞性肺疾病[例(%)]	4(6.2)	1(3.8)	3(7.7)	0.644
结核[例(%)]	5(7.7)	2(7.7)	3(7.7)	1.000
皮肤病[例(%)]	7(10.8)	3(11.5)	4(10.3)	1.000
胆道疾病[例(%)]	9(13.8)	5(19.2)	4(10.3)	0.509

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表 4 65例老年DILF患者的药物使用情况

药物类别	二级分类	例数	构成比(%)	具体用药
化学药	心脑血管药	7	10.8	阿托伐他汀钙、氟伐他丁、胺碘酮、奎尼丁
	降压药	6	9.2	倍他乐克、硝苯地平、卡托普利、依那普利
	抗生素	5	7.7	克林霉素、阿奇霉素、螺旋霉素、洛美沙星、阿莫西林-克拉维酸盐
	抗结核	5	7.7	异烟肼、利福平、吡嗪酰胺、乙胺丁醇、利福喷丁
	解热镇痛药	5	7.7	含对乙酰氨基酚(感康/扑热息痛/快克/感冒灵/速效感冒胶囊)、尼美舒利、布洛芬、安乃近
	抗肿瘤药	5	7.7	环磷酰胺、卡铂、吉西他滨
	神经用药	4	6.2	盐酸帕罗西汀、利培酮、米氮平、佳乐定
	降糖药	4	6.2	格列吡嗪、格列本脲、二甲双胍
	免疫抑制剂	2	3.1	来氟米特、柳氮磺吡啶
中药类	中草药	15	23.1	何首乌、土三七、补骨脂、雷公藤等
	中成药	23	35.4	脑血康胶囊、复方丹参片、银杏叶滴丸、天麻首乌胶囊、血府逐瘀胶囊、养血清脑颗粒、心元胶囊、安神补心胶囊、牛黄降压丸、决明降酯片、宫瘤消胶囊、金乌骨通胶囊、仙灵骨葆、血脂康、前列通、正胃片、三九胃泰、清开灵、百消丸、独一味胶囊、摩罗丹、肠胃宁、白癜灵
生物制剂	保健品	13	20.0	长寿因子酒、延寿片、鲅鱼油、西洋参
	其他	5	7.7	染发剂、油漆

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