發(fā)布時間：2018-05-19 12:40

  本文選題：藥物性肝損害 + 回顧性調(diào)查��； 參考：《復旦大學》2014年碩士論文

【摘要】：[背景]藥物性肝損害(drug-induced liver injury, DILI)的發(fā)病率逐漸上升,成為慢性肝病的主要病因。不同國家和地區(qū)DILI的患病率不同,目前尚缺乏中國地區(qū)的流行病學資料,尤其對于老年患者的DILI目前我國缺乏相關報道,而老齡化又是需要重視的問題。本調(diào)查旨在分析我院老年人群DILI的臨床特點并作相關預后等影響因素的分析。[目的]回顧性調(diào)查分析華東醫(yī)院第一診斷為DILI的年齡大于60歲的老年住院患者,探討老年DILI的流行病學、病因、臨床特點、及預后影響因素,提高臨床對DILI的認識,及時識別該病并改善預后。1、綜合分析老年DILI的主要受累藥物、伴隨用藥危險性、用藥時間、病程、性別分布、臨床特點及各項臨床指標的特點及變化規(guī)律,進一步討論老年人DILI的疾病特點。2、根據(jù)DILI的類型分類分別比較和統(tǒng)計處理,觀察各臨床指標與肝損害類型的關系及相關因素。3、綜合分析患者的預后情況,并通過對預后的分類統(tǒng)計,分析藥物種類、伴隨藥物、給藥途徑、性別、臨床分型、合并疾病及起病時生化免疫指標等因素對預后的影響。為日后對于該病的老年患者臨床用藥、該藥引起肝損害的可能性及治療提供參考。[方法]對2000年-2012年我院住院患者出院第一診斷為藥物性肝損害的86例老年患者進行回顧性收集患者性別、職業(yè)、引起肝損害藥物、伴隨藥物、臨床表現(xiàn),生化免疫檢查,輔助檢查,伴隨疾病,過敏,和預后等綜合分析,關注老年人DILI的臨床特點及規(guī)律。[結(jié)果]1、本研究藥物性肝損害患者共86人,男性37人,女性49人,比例約為1：1.32,年齡在60歲-89歲之間,平均年齡73.98±7.67歲。其中按DILI的類型分類肝細胞性肝損害39人(45.3%),膽汁淤積性32人(37.2%),混合型肝損害5人(5.8%),肝功能異常10人(11.6%)。按給藥途徑分類經(jīng)口服藥物引起肝損害62人(72.1%),經(jīng)靜脈藥物引起肝損害24人(27.9%)。2、引起DILI的藥物種類：以中草藥為主(31.4%),其次分別為抗生素(10.5%)、激素類(10.5%)、他汀類降脂藥物(9.3%),其他藥物種類還包括化療藥物、降糖藥、神經(jīng)精神類、NSAID等,伴隨用藥中最多見的為心血管類、抗生素類及保健品。其中引起DILI的口服藥物中最常見為中草藥,靜脈藥物為化療藥。3、引起DILI的基礎疾病主要以高血壓(36.6%)、2型糖尿病(16.1%)最多見,另外還見于膽囊炎、膽石癥,高脂血癥、冠心病、心律失常、腦梗塞及慢性腎功能不全等。4、臨床表現(xiàn)：特異性不明顯,最常見的首發(fā)癥狀是納差、厭食(21.5%)、其他表現(xiàn)為乏力(14%)、尿色加深(19.4%)、黃疸(15%)、腹部不適(腹脹、腹痛)(12.9%),腹瀉1.1%,消瘦1.1%,另外還有15.1%的患者無不適表現(xiàn),因體檢發(fā)現(xiàn)肝功能異常就診。肝外表現(xiàn)有發(fā)熱4人(4.7%),皮疹、皮膚瘙癢8人(9.3%)。從服用肝損害藥物到發(fā)現(xiàn)癥狀所用時間最短2天,最長6年,中位時間為30天。從停止肝損害藥物到癥狀恢復時間最短時間3天,最長時間270天,中位恢復時間為15天。DILI的平均病程為19.5±39.3天。其中從服用藥物到發(fā)現(xiàn)癥狀時間、停藥到癥狀好轉(zhuǎn)時間以及平均病程與肝損害類型、用藥途徑等因素無統(tǒng)計學差異。5、生化免疫檢查：特異性不強。在DILI的老年患者中實驗室檢查出現(xiàn)異常的頻率丙氨酸氨基轉(zhuǎn)移酶(alanine aminotransferance, ALT) 98.8%天門冬氨酸氨基轉(zhuǎn)移酶(aspartate aminotransferanc, AST) 92.8%堿性磷酸酶(alkaline phosphatase, ALP)55.1%,谷氨酰轉(zhuǎn)移酶(y-glutamyl transfease, GGT)83.5%,總膽紅素(total bilirubin, TBIL) 51.3%,間接膽紅素(Inderect bilirubin, IBIL)64.5%,直接膽紅素(derect bilirubin, DBIL) 39.5%。故上述指標敏感性較高,通過檢查上述實驗室指標可以篩查出肝損害的患者,但特異性低,對DILI的診斷無特異性。另外,ALT、AST、ALP、GGT的升高范圍多分布在10倍的正常值上限(upper limit of normal, ULN)以內(nèi)。6、DILI分型(肝細胞性、膽汁淤積性、混合型及肝功能異常)4組間ALT、AST、ALP及GGT差異有統(tǒng)計學意義,與膽汁淤積型及混合型組比較,肝細胞損傷型ALT、AST升高(P0.01),而ALP、GGT在膽汁淤積型組則較高(P0.01)。7、給藥途徑與各因素分析發(fā)現(xiàn),與靜脈給藥相比,口服給藥患者GGT水平較高,而靜脈給藥更容易出現(xiàn)再用藥反應現(xiàn)象,但給藥途徑與病程、用藥到發(fā)現(xiàn)癥狀、停藥到癥狀好轉(zhuǎn)的時間上無統(tǒng)計學差異。8、治療及轉(zhuǎn)歸：經(jīng)確診為藥物性肝損傷后停止引起肝損藥物,全部給予內(nèi)科保守治療,使用多烯磷脂酰膽堿,還原型谷胱甘肽及甘草酸二銨等保肝藥物,同時給予補充蛋白及熱量等支持治療。痊愈37人,好轉(zhuǎn)46人,死亡2人。預后情況與肝損類型及給藥途徑無統(tǒng)計學差異。9、性別、生化免疫指標、臨床分型及合并疾病等因素與患者預后分析發(fā)現(xiàn),起病時AST、GGT等能很好的預測老年DILI患者的預后,AST、GGT較高者提示預后不良。隨著年齡的增加膽紅素水平顯著升高,且TBIL、IBIL、DBIL均不同程度升高,具有統(tǒng)計學差異。老年DILI患者甘油三酯水平與性別相關,男性高于女性。老年DILI患者伴隨用藥的現(xiàn)象普遍,隨著年齡升高,伴隨用藥的種類越多,其中伴隨用藥多伴有首發(fā)AST及嗜酸性粒細胞升高,差異具有統(tǒng)計學意義。[結(jié)論]本資料研究老年DILI的特點總結(jié)如下：引起DILI的藥物種類以中草藥為主,其次分別為抗生素、激素類、他汀類降脂藥物。其中口服藥物中最常見為中草藥,靜脈藥物為化療藥。首發(fā)癥狀是納差、厭食,另外很多患者無不適表現(xiàn),因體檢發(fā)現(xiàn)肝功能異常就診。肝外表現(xiàn)有發(fā)熱,皮疹、皮膚瘙癢。與靜脈給藥相比,口服給藥患者GGT水平較高,而靜脈給藥更容易出現(xiàn)再用藥反應現(xiàn)象。肝細胞損傷型ALT、AST升高,而ALP、GGT在膽汁淤積型組則較高。起病時AST、GGT等能很好的預測老年DILI患者的預后,AST、GGT較高者提示預后不良。隨著年齡的增加膽紅素水平顯著升高,且TBIL、IBIL、DBIL均不同程度升高。老年DILI患者甘油三酯水平與性別相關。老年DILI患者伴隨用藥的現(xiàn)象普遍,隨著年齡升高,伴隨用藥的種類越多,其中伴隨用藥多伴有首發(fā)AST及嗜酸性粒細胞升高。
[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.
【學位授予單位】：復旦大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R595.3

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