86例老年药物性肝损害分析及预后影响因素的评估

发布时间：2018-05-19 12:40

本文选题：药物性肝损害 + 回顾性调查　；参考：《复旦大学》2014年硕士论文

【摘要】：[背景]药物性肝损害(drug-induced liver injury, DILI)的发病率逐渐上升,成为慢性肝病的主要病因。不同国家和地区DILI的患病率不同,目前尚缺乏中国地区的流行病学资料,尤其对于老年患者的DILI目前我国缺乏相关报道,而老龄化又是需要重视的问题。本调查旨在分析我院老年人群DILI的临床特点并作相关预后等影响因素的分析。[目的]回顾性调查分析华东医院第一诊断为DILI的年龄大于60岁的老年住院患者,探讨老年DILI的流行病学、病因、临床特点、及预后影响因素,提高临床对DILI的认识,及时识别该病并改善预后。1、综合分析老年DILI的主要受累药物、伴随用药危险性、用药时间、病程、性别分布、临床特点及各项临床指标的特点及变化规律,进一步讨论老年人DILI的疾病特点。2、根据DILI的类型分类分别比较和统计处理,观察各临床指标与肝损害类型的关系及相关因素。3、综合分析患者的预后情况,并通过对预后的分类统计,分析药物种类、伴随药物、给药途径、性别、临床分型、合并疾病及起病时生化免疫指标等因素对预后的影响。为日后对于该病的老年患者临床用药、该药引起肝损害的可能性及治疗提供参考。[方法]对2000年-2012年我院住院患者出院第一诊断为药物性肝损害的86例老年患者进行回顾性收集患者性别、职业、引起肝损害药物、伴随药物、临床表现,生化免疫检查,辅助检查,伴随疾病,过敏,和预后等综合分析,关注老年人DILI的临床特点及规律。[结果]1、本研究药物性肝损害患者共86人,男性37人,女性49人,比例约为1：1.32,年龄在60岁-89岁之间,平均年龄73.98±7.67岁。其中按DILI的类型分类肝细胞性肝损害39人(45.3%),胆汁淤积性32人(37.2%),混合型肝损害5人(5.8%),肝功能异常10人(11.6%)。按给药途径分类经口服药物引起肝损害62人(72.1%),经静脉药物引起肝损害24人(27.9%)。2、引起DILI的药物种类：以中草药为主(31.4%),其次分别为抗生素(10.5%)、激素类(10.5%)、他汀类降脂药物(9.3%),其他药物种类还包括化疗药物、降糖药、神经精神类、NSAID等,伴随用药中最多见的为心血管类、抗生素类及保健品。其中引起DILI的口服药物中最常见为中草药,静脉药物为化疗药。3、引起DILI的基础疾病主要以高血压(36.6%)、2型糖尿病(16.1%)最多见,另外还见于胆囊炎、胆石症,高脂血症、冠心病、心律失常、脑梗塞及慢性肾功能不全等。4、临床表现：特异性不明显,最常见的首发症状是纳差、厌食(21.5%)、其他表现为乏力(14%)、尿色加深(19.4%)、黄疸(15%)、腹部不适(腹胀、腹痛)(12.9%),腹泻1.1%,消瘦1.1%,另外还有15.1%的患者无不适表现,因体检发现肝功能异常就诊。肝外表现有发热4人(4.7%),皮疹、皮肤瘙痒8人(9.3%)。从服用肝损害药物到发现症状所用时间最短2天,最长6年,中位时间为30天。从停止肝损害药物到症状恢复时间最短时间3天,最长时间270天,中位恢复时间为15天。DILI的平均病程为19.5±39.3天。其中从服用药物到发现症状时间、停药到症状好转时间以及平均病程与肝损害类型、用药途径等因素无统计学差异。5、生化免疫检查：特异性不强。在DILI的老年患者中实验室检查出现异常的频率丙氨酸氨基转移酶(alanine aminotransferance, ALT) 98.8%天门冬氨酸氨基转移酶(aspartate aminotransferanc, AST) 92.8%碱性磷酸酶(alkaline phosphatase, ALP)55.1%,谷氨酰转移酶(y-glutamyl transfease, GGT)83.5%,总胆红素(total bilirubin, TBIL) 51.3%,间接胆红素(Inderect bilirubin, IBIL)64.5%,直接胆红素(derect bilirubin, DBIL) 39.5%。故上述指标敏感性较高,通过检查上述实验室指标可以筛查出肝损害的患者,但特异性低,对DILI的诊断无特异性。另外,ALT、AST、ALP、GGT的升高范围多分布在10倍的正常值上限(upper limit of normal, ULN)以内。6、DILI分型(肝细胞性、胆汁淤积性、混合型及肝功能异常)4组间ALT、AST、ALP及GGT差异有统计学意义,与胆汁淤积型及混合型组比较,肝细胞损伤型ALT、AST升高(P0.01),而ALP、GGT在胆汁淤积型组则较高(P0.01)。7、给药途径与各因素分析发现,与静脉给药相比,口服给药患者GGT水平较高,而静脉给药更容易出现再用药反应现象,但给药途径与病程、用药到发现症状、停药到症状好转的时间上无统计学差异。8、治疗及转归：经确诊为药物性肝损伤后停止引起肝损药物,全部给予内科保守治疗,使用多烯磷脂酰胆碱,还原型谷胱甘肽及甘草酸二铵等保肝药物,同时给予补充蛋白及热量等支持治疗。痊愈37人,好转46人,死亡2人。预后情况与肝损类型及给药途径无统计学差异。9、性别、生化免疫指标、临床分型及合并疾病等因素与患者预后分析发现,起病时AST、GGT等能很好的预测老年DILI患者的预后,AST、GGT较高者提示预后不良。随着年龄的增加胆红素水平显著升高,且TBIL、IBIL、DBIL均不同程度升高,具有统计学差异。老年DILI患者甘油三酯水平与性别相关,男性高于女性。老年DILI患者伴随用药的现象普遍,随着年龄升高,伴随用药的种类越多,其中伴随用药多伴有首发AST及嗜酸性粒细胞升高,差异具有统计学意义。[结论]本资料研究老年DILI的特点总结如下：引起DILI的药物种类以中草药为主,其次分别为抗生素、激素类、他汀类降脂药物。其中口服药物中最常见为中草药,静脉药物为化疗药。首发症状是纳差、厌食,另外很多患者无不适表现,因体检发现肝功能异常就诊。肝外表现有发热,皮疹、皮肤瘙痒。与静脉给药相比,口服给药患者GGT水平较高,而静脉给药更容易出现再用药反应现象。肝细胞损伤型ALT、AST升高,而ALP、GGT在胆汁淤积型组则较高。起病时AST、GGT等能很好的预测老年DILI患者的预后,AST、GGT较高者提示预后不良。随着年龄的增加胆红素水平显著升高,且TBIL、IBIL、DBIL均不同程度升高。老年DILI患者甘油三酯水平与性别相关。老年DILI患者伴随用药的现象普遍,随着年龄升高,伴随用药的种类越多,其中伴随用药多伴有首发AST及嗜酸性粒细胞升高。
[Abstract]:[background] the incidence of drug-induced liver injury (DILI) is increasing gradually, and it has become the main cause of chronic liver disease. The prevalence of DILI in different countries and regions is different, and there is still a lack of epidemiological data in China, especially for the DILI in the elderly patients. The purpose of this survey is to analyze the clinical characteristics of DILI in the elderly and analyze the factors affecting the prognosis. [Objective] to review and analyze the first diagnosis of DILI in the elderly hospitalized patients older than 60 years old in East China Hospital, and to explore the epidemiology, etiology, clinical characteristics and prognostic factors of the elderly DILI, and to improve the prognostic factors. The understanding of DILI, identifying the disease in time and improving the prognosis of.1, comprehensive analysis of the main involved drugs of old DILI, with the risk of drug use, the time of drug use, the course of the disease, the sex distribution, the characteristics of clinical characteristics and various clinical indexes, and the changes of the characteristics and changes of the clinical characteristics of the elderly, and further discuss the characteristics of the disease of the elderly DILI,.2, according to the classification of DILI. And statistical treatment, the relationship between the clinical indexes and the types of liver damage and the related factors.3 were observed. The prognosis of the patients was analyzed synthetically, and the effects on the prognosis were analyzed by the classification statistics of the prognosis, the drugs, the way of administration, the sex, the clinical typing, the combination of the disease and the biochemical and immune indexes at the onset of the disease. The clinical medication of the elderly patients with this disease, the possibility and the reference of the liver damage caused by this medicine. [Methods] a retrospective collection of 86 elderly patients who were first diagnosed as drug-induced liver damage in the hospital of our hospital in -2012 2000 was a retrospective collection of the patients' sex, occupation, liver damage drugs, drugs, clinical manifestations, biochemical and immunologic tests. Examination, auxiliary examination, combined with disease, allergy, and prognosis, a comprehensive analysis of the clinical characteristics and rules of DILI in the elderly. [results]1, 86 patients, 37 men, 49 women, 49 women, 60 years of age at the age of 60 years, and the average age of 73.98 + 7.67 years, of which were classified according to the type of DILI. Liver damage was 39 (45.3%), cholestasis was 32 (37.2%), mixed liver damage was 5 (5.8%), and liver dysfunction was 10 (11.6%). 62 people (72.1%) were caused by oral administration by oral administration, 24 (27.9%).2 of liver damage caused by intravenous drugs (27.9%) were induced by intravenous drugs. The types of DILI were cited as Chinese herbal medicine (31.4%) and antibiotic (10.5), respectively. %), hormone (10.5%), statins lipid lowering drugs (9.3%), other kinds of drugs including chemotherapeutic drugs, hypoglycemic drugs, Neuropsychiatry, NSAID and so on. The most common in the drug use are cardiovascular, antibiotics and health products. Among them, the most common oral medicine in DILI is the Chinese herbal medicine, and the intravenous drug is the chemotherapy drug.3, which causes the basic disease of DILI. Most of them were hypertension (36.6%) and type 2 diabetes (16.1%), which were also seen in cholecystitis, cholelithiasis, hyperlipidemia, coronary heart disease, arrhythmia, cerebral infarction and chronic renal dysfunction. The clinical manifestations were not obvious, the most common symptoms were anorexia (21.5%), other manifestations of anorexia (14%), urinary color deepening (19.4%), and yellow. Jaundice (15%), abdominal discomfort (abdominal distension, abdominal pain) (12.9%), diarrhoea 1.1%, thinning 1.1%, and 15.1% of the patients who had an unsuitable manifestation of abnormal liver function. The extrahepatic manifestations included 4 fever (4.7%), rash, and 8 skin pruritus (9.3%). The shortest time was 2 days from taking the liver damage drugs to the symptoms, and the median time was 30. The median time was 30. The shortest time from stopping liver damage drugs to symptom recovery time was 3 days, the longest time was 270 days, the average course of median recovery time of 15 days was 19.5 + 39.3 days, and there was no statistical difference between the drugs and the symptom time, the time of stopping to the improvement of the symptoms, the average course of the disease and the type of liver damage, and the way of drug use, such as.5, Biochemical immunoassay: the specificity is not strong. The abnormal frequency of alanine aminotransferase (alanine aminotransferance, ALT) 98.8% aspartate aminotransferase (aspartate aminotransferanc, AST) 92.8% alkaline phosphatase (alkaline phosphatase, ALP) 55.1%, glutamyl transferase (Y-G) in the elderly patients in the DILI Lutamyl transfease, GGT) 83.5%, total bilirubin (total bilirubin, TBIL) 51.3%, indirect bilirubin (Inderect bilirubin, IBIL) 64.5%, direct bilirubin (derect bilirubin, DBIL) therefore the above index sensitivity is high, by examining the above laboratory indicators can screen out patients with liver damage, but the specificity is low, the diagnosis of no In addition, the range of ALT, AST, ALP, GGT increased in 10 times the upper limit of normal value (upper limit of normal, ULN),.6, DILI typing (hepatotoxicity, cholestasis, mixed type and liver dysfunction) of the 4 groups were statistically significant, compared with the cholestasis type and mixed group, liver cell damage type ST increased (P0.01), while ALP and GGT were higher in the cholestasis group (P0.01).7. The way of administration and the analysis of various factors found that the level of GGT in the oral administration was higher than that of the intravenous administration, while the intravenous administration was more likely to reappear the redrug reaction, but the route of administration and the course of the administration, the medication to the symptoms, the time of stopping to the improvement of the symptoms were no common. Study difference.8, treatment and outcome: after the diagnosis of drug induced liver injury to stop causing liver damage drugs, all given internal medicine conservative treatment, using polyene phosphatidylcholine, also archetypal glutathione and diammonium glycyrrhizinate and other liver preservation drugs, simultaneously giving supplemental protein and calorie support treatment. Cure 37 people, improve 46 people, death 2 people. There was no statistical difference between the status and the type of liver damage and the way of drug delivery.9, sex, biochemical immune index, clinical classification and combined disease and patient prognosis analysis found that AST, GGT and so on can predict the prognosis of elderly DILI patients well at the onset of the disease, AST, GGT with higher prognosis. With the increase of age, the level of bilirubin is significantly increased, and TBIL, IBIL, DBIL were all higher in different degrees, with statistical difference. The level of triglyceride in elderly patients with DILI was related to sex, male was higher than that of women. The prevalence of drug use in elderly patients with DILI was common, with the increase of age, the more kinds of drugs were accompanied by the increase of first AST and eosinophil, the difference was statistically significant. [Conclusion] the characteristics of the study of DILI in the elderly are summarized as follows: the main types of drugs that cause DILI are Chinese herbal medicine, followed by antibiotics, hormones, and statins. The most common oral medicine is Chinese herbal medicine, and intravenous drugs are chemotherapeutic drugs. The first symptoms are anorexia and anorexia. Physical examination found abnormal liver function. Extrahepatic manifestations were fever, rash, and itchy skin. Compared with intravenous administration, the level of GGT was higher in patients with oral administration, while intravenous administration was more likely to be reused. ALT, AST increased, while ALP, GGT was higher in the cholestasis group. AST, GGT, etc. could be well predicted at the onset of the disease. The prognosis of DILI patients in the year of AST and higher GGT showed poor prognosis. With the increase of age, the level of bilirubin increased significantly, and TBIL, IBIL, DBIL were all elevated in different degrees. The level of triglyceride in elderly patients with DILI was related to sex. The incidence of medication in elderly DILI patients was common, with the increase of age, the more types of drugs were accompanied by the use of drugs. Most drugs were accompanied by elevated AST and eosinophils.
【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R595.3

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