两种不同定义标准的慢性药物性肝损伤临床研究

肝脏 ›› 2020, Vol. 25 ›› Issue (6): 569-572.

两种不同定义标准的慢性药物性肝损伤临床研究

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

100039 北京解放军总医院第五医学中心中医科(王丽苹, 朱云, 王仲霞, 王立福, 孙永强, 景婧, 许文涛, 余思邈, 桑秀秀, 田淼, 任岳波, 王睿林);
中西医结合科(何婷婷);
河南中医药大学第一附属医院(崔延飞)

出版日期:2020-06-30 发布日期:2020-07-16
通讯作者: 王睿林, Email:WRL7905@163.com
基金资助:
国家自然科学基金项目资助(81673806);保健专项科研课题(17BJZ53)

Clinical study of two diagnostic criteria for chronic drug-induced liver injury

WANG Li-ping¹, HE Ting-ting², ZHU Yun¹, WANG Zhong-xia¹, WANG Li-fu¹, SUN Yong-qiang¹, JING Jing¹, XU Wen-tao¹, YU Si-miao¹, SANG Xiu-xiu¹, TIAN Miao¹, REN Yue-bo¹, CUI Yan-fei³, WANG Rui-lin¹

1. Department of Traditional Chinese Medicine, the Fifth Medical Center of PLA General Hospital;
2.Department of Integrated Chinese and Western Medicine, the fifth medical center of PLA General Hospital;
3.The First Affiliated Hospital of Henan University of Chinese Medicine

Online:2020-06-30 Published:2020-07-16
Contact: WANG Rui-lin, Email: WRL7905@163.com

摘要/Abstract

摘要： 目的评价两种不同定义标准对慢性DILI的适用性, 以及DILI发病后第2个月TBil和ALP对DILI的预测价值。方法收集解放军总医院第五医学中心2015年1月-2018年6月收治的DILI 73例, 分别应用6个月和12个月两种诊断标准, 比较两种标准的诊断结果是否存在差异, 分析DILI发病后第2个月TBil和ALP仍持续升高对慢性DILI的预测情况。结果依据6个月诊断标准, 有65例符合慢性DILI诊断, 8例不符合慢性DILI的诊断, 发病后第2个月TBil>33.65 μmol/L对慢性DILI的发生有一定预测价值(P<0.05), 该界值处灵敏度88%, 特异度61%;发病后第2个月ALP水平对慢性DILI的发生无预测价值。依据12个月诊断标准, 有51例符合慢性DILI诊断, 22例不符合慢性DILI的诊断, 发病后第2个月ALP和TBil水平对慢性DILI的发生均无预测价值。两种不同标准诊断结果差异有统计学意义(P<0.05), 6个月标准时慢性DILI检出率高于12个月标准, 有43例患者可同时满足两种诊断标准。结论 DILI发病后第2个月TBil持续升高对我国慢性DILI的预测价值优于ALP, 建议治疗时主要参考6个月定义标准, 诊断时可参考12个月定义标准。

关键词: 慢性药物性肝损伤, 诊断, 临床研究

Abstract: Objective To evaluate the applicability of 2 different diagnostic criteria for chronic drug-induced liver injury (DILI) in China and the predictive value of total bilirubin (TBil) and alkaline phosphatase (ALP) at the second month after the onset of DILI.Methods A total of 73 cases of chronic DILI admitted to our hospital from January 2015 to June 2018 were enrolled. The patients were assessed by 6-month and 12-month diagnostic criteria, respectively. The diagnostic results of the 2 criteria were compared. The predictive value of TBil and ALP at the second month after the onset of DILI was analyzed.Results According to the 6-month diagnostic criterion, 65 cases were in accordance with the diagnosis of chronic DILI, and 8 cases were not. The best predictive threshold of TBil at the second month was 33.65 umol/L, with a sensitivity of 88% and a specificity of 61%. The level of ALP at the second month had no predictive value. According to the 12-month diagnostic criterion, 51 cases were in accordance with the diagnosis of chronic DILI, 22 cases were not. The levels of TBil and ALP at the second month both had no predictive value. Between the 2 criteria, there were significant differences (P<0.05). The detection rate of 6-month criterion was higher than that of 12-month criterion, and 43 patients met the 2 criteria at the same time.Conclusion At the second month after the onset of DILI, the predictive value of TBil was higher than that of ALP. According to the standard definition of chronic DILI, in consideration of diagnostic efficacy and the situation of DILI in China, it is suggested to refer to the 6-month diagnostic criterion for treatment and 12-month diagnostic criterion for diagnosis.

Key words: Chronic drug-induced liver injury, Diagnose, Clinical study

王丽苹, 何婷婷, 朱云, 王仲霞, 王立福, 孙永强, 景婧, 许文涛, 余思邈, 桑秀秀, 田淼, 任岳波, 崔延飞, 王睿林. 两种不同定义标准的慢性药物性肝损伤临床研究[J]. 肝脏, 2020, 25(6): 569-572.

WANG Li-ping, HE Ting-ting, ZHU Yun, WANG Zhong-xia, WANG Li-fu, SUN Yong-qiang, JING Jing, XU Wen-tao, YU Si-miao, SANG Xiu-xiu, TIAN Miao, REN Yue-bo, CUI Yan-fei, WANG Rui-lin. Clinical study of two diagnostic criteria for chronic drug-induced liver injury[J]. Chinese Hepatolgy, 2020, 25(6): 569-572.

参考文献 11

[1]	European Association for the Study of the Liver. EASL clinical practice guidelines: Drug - induced liver injury. J Hepatol, 2019.
[2]	于乐成, 赖荣陶, 陈成伟, 等.《2019年欧洲肝病学会临床实践指南:药物性肝损伤》精粹及评析.临床肝胆病杂志, 2019, 35:1242-1250.
[3]	于乐成, 茅益民, 陈成伟, 等.药物性肝损伤诊治指南.临床肝胆病杂志, 2015, 31:1752-1769.
[4]	肖小河, 李秀惠, 朱云, 等.中草药相关肝损伤临床诊疗指南.临床肝胆病杂志, 2016, 32:835-843.
[5]	Fontana RJ, Watking PB, Bonkovsky HL, et al. Drug-induced liver injury network (DILIN) prospective study:rationale, design and conduct. Drug Saf, 2009, 32:55-68.
[6]	Chalasani N, Fontana RJ, Bonkovsky HL, et al. Drug Induced Liver Injury Network (DILIN). Causes, clinical features and outcomes from a prospective study of drug-induced liver injury in the United States.Gastroenterology, 2008, 135:1924-1934.
[7]	Fontana RJ, Hayashi PH, Gu J, et al. DILIN Network, Idiosyncratic drug-induced liver injury is associated with substantial morbidity and mortality within 6 months from onset. Gastroenterology, 2014, 147:96-108.
[8]	Medina-Caliz I, Robles-Diaz M, Garcia-Mu oz B, et al. Spanish DILI Registry. Definition and risk factors for chronicity following acute idiosyncratie drug-induced liver injury. J Hepatol, 2016, 65:532-542.
[9]	Andrade RJ, Lucena MI, Kaplowitz N, et al. Outcome of acute idiosyncratic drug-induced liver injury:Long-term follow-up in a hepatotoxicity egistry. Hepatology, 2006, 44:1581-1588.
[10]	Fontana RJ, Hayashi PH, Barnhart H, et al. Persistent liver biochemistry abnormalities are more common in older patients and those with cholestatic drug induced liver injury. Am J Gastroenterol, 2015, 110:1450-1459.
[11]	黄昂, 梁庆升, 孙颖, 等. 慢性药物性肝损伤的诊治研究进展.传染病信息, 2018, 31:105-107.
[12]	Sebode M, Schulz L, Lohse AW. “Autoimmune(-Like)”drug and herb induced liver injury:new insights into molecular pathogenesis. Int J Mol Sci, 2017, 18.
[13]	Kleiner DE, Chalasani NP, Lee WM, et al. Hepatic histological findings in suspected drug-induced liver injury:systematic evaluation and clinical associations.Hepatology, 2014, 59:661-670.
[14]	王绮夏, 蒋翔, 连敏, 等. 2015年欧洲肝病学会临床实践指南:自身免疫性肝炎.临床肝胆病杂志, 2015, 31:2000-2019.
[15]	Zhu Y, Niu M, Chen J, et al.Specialized Committee for Drug-Induced Liver Diseases, Division of Drug-Induced Diseases, Chinese Pharmacological Society.Comparison between Chinese herbal medicine and Western medicine-induced liver injury of 1985 patients. J Gastroenterol Hepatol, 2016, 31:1476-82.
[11]	Bjornsson E, Kalaitzakis E, Av Klinteberg V, et al. Long-term follow-up of patients with mild to moderate drug-induced liver injury . Aliment Pharmacol Ther, 2007, 26:79-85.