不同类型的急性药物性肝损伤患者临床特征比较
DOI: 10.3969/j.issn.1001-5256.2021.03.025
Clinical features of patients with different types of acute drug-induced liver injury: A comparative analysis
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摘要:
目的 回顾性分析不同类型急性药物性肝损伤(DILI)患者的临床结局。 方法 收集2010年12月-2019年3月首都医科大学附属北京佑安医院和北京同仁医院诊断为急性DILI的790例患者的临床资料,根据受损靶细胞类型分为肝细胞损伤型(n=554)、胆汁淤积型(n=99)、混合型(n=137)3组。对患者进行严重程度分级评分、临床结局以及Hy′s法则评估。符合正态分布的计量资料3组间比较采用方差分析,进一步两两比较采用LSD-t检验; 不符合正态分布的计量资料组间比较采用Kruskal-Wallis H检验。计数资料3组间比较采用χ2检验。等级资料3组间比较采用Kruskal-Wallis H检验,2组间比较采用Mann-Whitney U检验。 结果 3组患者均以女性多见,肝细胞损伤型女性比例(70.8%)显著高于胆汁淤积型(54.5%),胆汁淤积型显著低于混合型(54.7%)(P值均<0.05)。肝细胞损伤型、胆汁淤积型和混合型严重程度差异有统计学意义(H=36.589,P<0.05), 各型重度患者分别为244(44.1%)例、56(56.6%)例和46(33.6%)例。引起肝损伤的药物包括中药、西药、中药与西药联用及其他,其中中药是最常见的原因。不同分型患者出院时结局比较差异有统计学意义(H=14.390,P=0.001);肝细胞损伤型患者的治愈率显著高于胆汁淤积型,而未愈率和病死率显著低于胆汁淤积型(P值均<0.05)。554例肝细胞损伤型DILI患者中符合Hy′s法则的有388例(70.0%),不符合的患者有166例(30.0%),2组患者的临床转归比较具有统计学差异(U=38 372.0,P=0.033), 不符合Hy′s法则组患者的预后较好。 结论 DILI患者多数为女性,以肝细胞损伤型为主。中药是导致肝损伤的主要原因。肝细胞损伤型和胆汁淤积型患者病情较重。DILI预后相对较好,病死率较低。Hy′s法则不能较好地预测急性DILI的死亡情况。 -
关键词:
- 化学性与药物性肝损伤 /
- 肝细胞损伤 /
- 胆汁淤积
Abstract:Objective To investigate the clinical features of patients with different types of acute drug-induced liver injury (DILI) through a retrospective analysis. Methods Clinical data were collected from 790 patients who were diagnosed with acute DILI in Beijing YouAn Hospital and Beijing Tongren Hospital affiliated to Capital Medical University from December 2010 to March 2019, and according to the type of damaged target cell, the patients were divided into hepatocellular injury type group with 554 patients, cholestasis type group with 99 patients, and mixed type group with 137 patients. The patients were evaluated based on severity grade and score, clinical outcome, and Hy′s rule. An analysis of variance was used for comparison of normally distributed continuous data between three groups, and the least significant difference t-test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups. The chi-square test was used for comparison of categorical data between three groups. The Kruskal-Wallis H test was used for comparison of ranked data between three groups, and the Mann-Whitney U test was used for comparison between two groups. Results Most of the patients were female in all three groups, and the hepatocellular injury type group had a significantly higher proportion of female patients than the cholestasis type group (70.8% vs 54.5%, P < 0.05), and the cholestasis type group had a significantly lower proportion of female patients than the mixed type group (54.5% vs 54.7%, P < 0.05). There were 244 patients with grade 3 hepatocellular injury type DILI (244/554, 44.1%), 56 patients with grade 3 cholestasis type DILI (56/99, 56.6%), and 46 patients with grade 3 mixed type DILI (46/137, 33.6%), and there was a significant difference between the three groups (χ2=36.589, P < 0.05). Drugs inducing liver injury included traditional Chinese medicine, Western medicine, combination of traditional Chinese medicine and Western medicine, and other drugs, among which traditional Chinese medicine was the most common cause of liver injury. There was a significant difference in the outcome at discharge between the patients with different types (H=14.390, P=0.001). Compared with the cholestasis type group, the hepatocellular injury type group had a significantly higher cure rate and significantly lower uncured rate and mortality rate (all P < 0.05). Among the 554 patients with hepatocellular injury type DILI, 388 (70.0%) met Hy′s rule and 166 (30.0%) did not meet Hy′s rule, and there was a significant difference in clinical outcome between these two groups (U=38 372.0, P=0.033). Conclusion DILI is more common in women, and most patients have hepatocellular injury type DILI. Traditional Chinese medicine is the main cause of liver injury. There is a high proportion of patients with severe DILI among the patients with hepatocellular injury type or cholestasis type. DILI often has good prognosis with a relatively low mortality rate. Hy′s rule cannot predict the death of patients with acute DILI. -
Key words:
- Chemical and Drug Induced Liver Injury /
- Hepatocyte Injury /
- Cholestasis
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表 1 3组患者临床资料的比较
指标 全部患者(n=790) 肝细胞损伤型(n=554) 胆汁淤积型(n=99) 混合型(n=137) 统计值 P值 年龄(岁) 52.0(37.0~60.0) 51.0(37.0~59.0) 52.0(35.0~63.0) 55.5(43.0~62.8) F=0.746 0.475 女性[例(%)] 521(65.9) 392(70.8) 54(54.5)1) 75(54.7)2) χ2=19.098 0.001 ALT(U/L) 518.3(229.0~966.0) 777.5(474.7~1163.5) 91.0(56.0~174.7) 195.0(123.0~283.0) H=416.398 <0.001 AST(U/L) 332.3(155.8~693.4) 482.2(256.0~827.4) 115.3(59.0~200.0) 157.0(82.0~241.5) F=164.492 <0.001 TBil(μmol/l) 105.8(33.9~232.7) 98.6(32.8~220.5) 178.7(93.2~345.7)1) 76.0(22.4~207.1)2) H=31.975 <0.001 ALP(U/L) 144.2(111.3~204.6) 134.9(106.0~181.0) 253.0(137.9~497.0) 158.0(117.9~233.0) H=73.576 <0.001 Alb(g/L) 37.0±5.3 37.9(34.3~40.9) 34.3(29.2~38.2)1) 36.9(33.1~40.5)2) H=33.784 <0.001 CR(μmol/l) 58.4(49.5~70.5) 59.0(50.1~70.6) 54.0(43.9~70.8) 57.1(48.4~70.1) H=5.840 0.054 PTA(%) 89.3(75.0~100.6) 89.0(75.0~99.6) 92.0(72.8~106.3) 91.9(79.2~102.6) F=0.669 0.513 INR 1.0(1.0~1.2) 1.0(1.0~1.2) 1.0(0.9~1.2) 1.0(1.0~1.1) F=0.760 0.468 严重程度[例(%)] H=36.589 <0.001 轻度 243(30.7) 178(32.1) 9(9.1) 56(40.9) 中度 107(13.5) 76(13.7) 11(11.1) 20(14.6) 重度 346(43.8) 244(44.1) 56(56.6) 46(33.6) ALF 82(10.4) 49(8.8) 21(21.2) 12(8.8) 死亡 12(1.5) 7(1.3) 2(2.0) 3(2.1) 住院时间(d) 20.0(14.0~29.0) 21.0(14.0~28.0) 25.0(14.0~33.0) 18.0(13.0~32.8) H=4.909 0.086 注:1)与肝细胞损伤型比较,P<0.05;2)与胆汁淤积型比较,P<0.05。年龄、AST和PTA经过log转换,INR经过1/平方转换后数据呈正态分布,3组间比较采用方差分析。 表 2 主要致病药物的情况
致病药物 例(%) 中药 346(43.8) 西药 255(32.3) 单种药物 191(74.9) 抗感染药物 55(28.8) 心血管药物 34(17.8) 非甾体抗炎药 27(14.1) 抗肿瘤药物或免疫调节药 25(13.1) 内分泌药 18(9.4) 精神障碍药物 11(5.8) 消化系统药物 9(4.7) 皮肤系统药物 5(2.6) 皮质激素药物 4(2.1) 多种药物 64(25.1) 中药联合西药 127(16.1) 其他 62(7.8) 表 3 不同类型DILI患者出院时临床疗效差异
组别 例数 治愈[例(%)] 好转[例(%)] 未愈[例(%)] 死亡[例(%)] 肝细胞损伤型 554 56(10.1) 473(85.4) 18(3.2) 7(1.3) 胆汁淤积型 99 3(3.0)1) 83(83.8) 10(10.1)1) 3(3.0)1) 混合型 137 11(8.0) 115(83.9) 8(5.8) 3(2.2) 注:1)与肝细胞损伤型比较,P<0.05。 表 4 Hy′s法则与患者临床转归
组别 例数 治愈[例(%)] 好转[例(%)] 未愈[例(%)] 死亡[例(%)] 符合Hy′s法则 388 34(8.8) 332(85.6) 17(4.4) 5(1.3) 不符合Hy′s法则 166 22(13.3) 141(84.9) 1(0.6) 2(1.2) -
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