103例药物性肝损伤的临床分析

发布时间：2018-12-17 17:29

【摘要】：我们于临床用药的过程里,因药物自身成分及/或经其代谢产生的物质,或者因机体本身体质的原因导致的高敏感性或较低的耐受性而引起的肝功能异常或结构改变称为药物性肝损伤(DILI)。现如今,在我国由于大量药物的频繁使用,药物性肝损伤(DILI)已经成为一种重要的肝脏疾病,正日益加深的影响着人类的身心健康。然而,DILI无特异性的临床症状及生化学指标改变,诊断仍面临困难,漏诊及误诊率较高。针对该难题,中华医学会肝病学分会于2015年发布我国第一个药物性肝损伤诊治指南,为药物性肝损伤的诊断治疗提供了依据。目的:依据药物性肝损伤诊断指南,对山东省立医院既往诊断为药物性肝损伤病例行重新诊断,分析符合诊断标准者临床特点,明确可引起肝损害的具体药物种类,引起肝损害的类型,对于以后临床用药、防止再次发生药物不良事件提供依据。方法:搜索山东大学附属山东省立医院2014年1月1日至2016年12月31日肝病科诊治的诊断为"药物性肝损伤"、"药物性肝炎"、"中毒性肝病"、"中毒性肝炎"病例128例,依据诊断指南对其再次诊断,排除掉RUCAM评分6分者25例,纳入依据诊断标准评定为极可能或很可能为药物性肝损伤者103例,进行回顾性研究,就其一般情况(如年龄、性别、职业)、临床特点(包括体征、辅助检查、临床分型)、导致肝功能异常的药物、治疗方法、治疗转归等情况进行统计研究。结果:1.纳入研究的病例中RUCAM评分8分所占比例最大(25.2%),其次为 7 分23.3%,9 分 22.3%,6分21.4%,10 分4.9%,12 分 1.9%,11 分 1.0%。2.药物性肝损伤发病率逐年增高。3.发病平均年龄为46.75 ± 16.11。其中41-60岁所占比例最大(44.7%)。4.导致药物性肝损伤的药物中,中药52例(43.7%),抗生素17例(14.3%),抗结核药9例(7.6%),减肥及保健品4例(3.4%),抗甲状腺药3例(2.5%),非甾体抗炎药3例(2.5%),保胃药5例(4.2%)。5.临床表现以恶心、纳差,厌油,腹痛、腹泻等消化道症状57例(43.8%),皮肤、巩膜黄染及/或小便发黄45例(34.6%),乏力12例(9.2%),皮疹、皮肤瘙痒2例(1.5%),无症状14例(10.8%)。6.临床分型:根据病程,急性药物性肝损伤94例(91.2%),慢性药物性肝损伤9例(8.8%);根据靶细胞类型,肝细胞型90例(87.4%),胆汁淤积型7例(6.8%),混合型6例(5.8%)。肝细胞型DILI ALT、AST水平较高,胆汁淤积性DILI GGT、ALP水平较高(P0.05)。7.临床转归:治疗好转出院92例(89.3%),未见明显好转自动出院9例(8.8%),死亡2例(1.9%)。结论:药物性肝损伤(DILI)的发病率正一年高于一年,现已经成为主要的肝功能及结构损害原因之一。以女性及中老年人多见,临床表现中以消化症状最多见。可以引起药物性肝损伤的药物为:中药,抗生素,抗结核药,减肥药及保健品,抗甲状腺药,非甾体抗炎药,保胃药。急性DILI以及肝细胞型DILI最常见。患者大多预后良好。
[Abstract]:In the course of clinical use of drugs, the substances produced by the drug's own components and / or by its metabolism, Or liver dysfunction or structural change caused by high sensitivity or low tolerance due to the body's own physical condition is called drug-induced liver injury (DILI). Nowadays, due to the frequent use of a large number of drugs in China, drug-induced liver injury (DILI) has become an important liver disease, which is increasingly affecting the physical and mental health of human beings. However, DILI has no specific clinical symptoms and biochemical indicators, so the diagnosis is still difficult, and the rate of missed diagnosis and misdiagnosis is high. In order to solve this problem, the Chinese Society of Hepatology issued the first guidelines for the diagnosis and treatment of drug-induced liver injury in 2015, which provides a basis for the diagnosis and treatment of drug-induced liver injury. Objective: according to the guidelines for the diagnosis of drug-induced liver injury, we rediagnosed the patients with drug-induced liver injury in Shandong Provincial Hospital, analyzed the clinical characteristics of those who met the diagnostic criteria, and determined the specific drugs that could cause liver injury. The types of liver damage may provide evidence for clinical use of drugs to prevent the recurrence of adverse drug events. Methods: from January 1, 2014 to December 31, 2016, the Department of Hepatology of Shandong Provincial Hospital affiliated to Shandong University diagnosed as "drug-induced liver injury", "drug-induced hepatitis", "toxic liver disease", and "toxic hepatitis" in 128 cases. According to the diagnostic guidelines, 25 patients with RUCAM score 6 were excluded, and 103 patients who were assessed as most likely or most likely to be drug-induced liver injury according to the diagnostic criteria were included in a retrospective study on the general situation (such as age, sex, etc.) Clinical features (including signs, adjuvant examinations, clinical typing), drugs leading to abnormal liver function, treatment methods, outcome of treatment, etc. Results: 1. The RUCAM score of 8 was the largest (25.2%), followed by 7: 23.3and 9: 22.3. The incidence of drug-induced liver injury increased year by year. The mean age of onset was 46.75 卤16.11. 41-60 years of age accounted for the largest proportion (44.7%). Among the drugs causing drug-induced liver injury, 52 cases (43.7%) were Chinese medicine, 17 cases (14.3%) were antibiotics, 9 cases (7.6%) were anti-tuberculosis drugs, 4 cases (3.4%) were slimming and health products. Antithyroid drugs were found in 3 cases (2.5%), non-steroidal anti-inflammatory drugs in 3 cases (2.5%), gastric preservatives in 5 cases (4.2%) and non-steroidal anti-inflammatory drugs in 5 cases (4.2%). The clinical manifestations were nausea, anorexia, oil, abdominal pain and diarrhea in 57 cases (43.8%), skin, yellowish sclera and / or urine yellowing in 45 cases (34.6%), fatigue in 12 cases (9.2%) and rash in 12 cases. There were 2 cases (1.5%) of pruritus and 14 cases (10.8%) of asymptomatic pruritus. Clinical classification: according to the course of disease, 94 cases (91.2%) were acute drug-induced liver injury, 9 cases (8.8%) were chronic drug-induced liver injury. According to target cell type, 90 cases (87.4%) were hepatocyte type, 7 cases (6.8%) were cholestasis type, 6 cases (5.8%) were mixed type. The level of hepatocyte DILI ALT,AST was higher, and the level of cholestatic DILI GGT,ALP was higher (P0.05). The clinical outcome: 92 cases (89. 3%) were cured, 9 cases (8. 8%) were left hospital without obvious improvement, 2 cases (1. 9%) died. Conclusion: the incidence of drug-induced liver injury (DILI) is more than one year and has become one of the main causes of liver function and structure damage. Most of them were female and middle aged, and digestive symptoms were most common in clinical manifestations. Drugs that can cause drug-induced liver injury are: traditional Chinese medicine, antibiotics, anti-tuberculosis drugs, diet and health products, anti-thyroid drugs, non-steroidal anti-inflammatory drugs, stomach protection drugs. Acute DILI and hepatocyte DILI are the most common. Most patients have a good prognosis.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R575

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