某院消化内科病房40例药物性肝损伤综合分析

目的 探讨药物性肝损伤病例发生的特点.方法 收集2011年1月-2015年12月某医院消化内科病房的药物性肝损伤病例,每例患者填写药品不良反应报告表,详细记录患者性别、年龄、可疑药品使用情况、药物性肝损伤发生及处理情况,并进行临床分型,将所有数据使用Excel软件进行统计分析.结果 共收集药物性肝损伤病例40例,其中女性18例,男性22例;＞45岁的中老年患者占所有发病人数的70％;中草药和中成药导致的药物性肝损伤共有25例,高达62.5％,其他依次为抗感染药物、免疫系统用药、消化系统用药、抗痛风药、心血管系统用药、内分泌系统用药.33例(82.50％)患者用药开始到肝损伤发生的时间在5～90 d.39例患者从停药开始到肝损伤发生的时间≤15 d,只有1例肝血管损伤型超过30 d.32例患者对症治疗后好转,8例由土三七导致的肝小静脉闭塞症无法逆转,留下后遗症.结论 临床药师应积极推动药物性肝损伤的防治工作,协助医师制定合理的药物治疗方案,避免药物滥用,以减少药物性肝损伤的发生.     

异甘草酸镁治疗抗结核药物性肝损伤82例疗效分析

目的：探讨异甘草酸镁治疗抗结核药物性肝损伤82例的疗效。方法82例经血清生化指标确认的由于使用抗结核药物引起药物性肝损伤患者,给予5%葡萄糖针250 ml+异甘草酸镁针150 mg,1次/d,静脉滴注,疗程3周,对其疗效进行分析。结果79例患者治愈,血清生化指标均正常,3例无效,总有效率96.34%,除1例患者出现眼睑浮肿,无高血压、低钾血症等发生。结论异甘草酸镁治疗抗结核药物性肝损伤,治疗后预后较好,副作用少。     

Plasma exchange treats severe intrahepatic cholestasis caused by dacomitinib: A case report

Rationale:Dacomitinib-induced liver injury is often manifested by mild elevations of transaminases and bilirubin, and severe intrahepatic cholestasis caused by dacomitinib for simultaneous taking orally cytochrome P450 2D6 (CYP2D6) competitive substrates has been rarely reported.Patient concerns:The patient was a 69-year-old woman with non–small cell lung cancer (NSCLC) who was prescribed oral dacomitinib for a month; she was given oral loratadine due to “allergic rhinitis” and metoprolol extended action tablets due to “tachycardia” separately for a few days during the course of dacomitinib treatment. The patient developed liver damage, increased fatigue, yellow urine, and pruritus, with significantly elevated serum levels of bilirubin and glutamyltranspetidase.Diagnosis:Intrahepatic cholestasis, drug-induced liver injury, and NSCLC.Interventions:After admission, the patient was prescribed adenosylmethionine, acetylcysteine, ursodeoxycholic acid capsule, methylprednisolone and fenofibrate for a month, with progressive elevation of liver biochemical parameters. Through drug enzyme gene assays in the liver tissue after percutaneous liver biopsy, we found both CYP2D6*10/*10 and ATP-binding cassette subfamily B member 1 GG variants (rs1045642) positive. After the poor response to the conventional medication, the patient underwent plasma exchange.Outcomes:The patient was discharged after her liver parameters improved; the parameters remained normal at several follow-up visits, and she renewed the NSCLC regimens without dacomitinib after being evaluated by oncologists.Lessons:Dacomitinib can induce severe intrahepatic cholestasis. It is considered that patients with intermediate metabolic CYP2D6 are susceptible to drug-induced liver injury caused by dacomitinib; plasma exchange may be an effective treatment.     

Metronidazole-induced hepatotoxicity in a patient with xeroderma pigmentosum: A case report

Rationale:Whereas metronidazole-induced hepatotoxicity is quite rare in the general population, in individuals carrying a nucleotide excision repair disorder, namely Cockayne syndrome, there is a high risk of developing this complication.Patient concerns:We report the case of a 44-year-old man, affected by xeroderma pigmentosum, who was admitted to the hospital presenting aspiration pneumoniae caused by worsening dysphagia and with severe hepatotoxicity during the hospitalization.Diagnoses:Acute hepatitis, which was leading to acute liver failure, occurred during antibiotic treatment with metronidazole and ceftazidime with an elevation of liver enzymes consistent with hepatocellular damage pattern.Interventions:Hydration with glucose 5% solution, pantoprazole and vitamin K were administered, meanwhile other causes of hepatitis were ruled out and the ongoing antibiotic treatment was stopped suspecting a drug-induced liver injury.Outcomes:Liver function nearly completely recovered 1 month later with a first rapid improvement, within few days, of aminotransferases and coagulation studies, and slower of cholestatic enzymes.Lessons:We describe the first case available in the literature of hepatotoxicity associated with metronidazole treatment in a xeroderma pigmentosum patient. Clinicians therefore, based on this report and according to the possible underlying mechanism shared by other genetic diseases characterized by alterations in the pathway of DNA-repair, should consider such adverse event also in patients affected by this rare disease.     

蒽环类化疗药物致兔组织损伤后处理的实验研究

目的比较蒽环类化疗药物静脉注射外渗后局部组织溃疡修复的三种方法。方法健康家兔分别采用柔红霉素、阿霉素和表阿霉素制成局部损伤模型后,肝素钠、低分子肝素钙和普鲁卡因环形封闭。结果局部组织溃疡多发生在1～2周内;经肝素钠和肝索钙局部封闭3周后局部溃疡的发生率和溃疡面积明显低于普鲁卡因和对照组（P＜0．05）;结论肝素钠和低分子肝素钙能降低蒽环类化疗药物外渗后所致溃疡的发生和缩小溃疡面积,而价格较低的肝素钠是值得临床推广应用的药物。     

特比萘芬引起药物性肝损害一例

63岁男性患者,因治疗灰指甲服用特比萘芬片0．25g,1次／d,6周后出现乏力、尿黄、巩膜黄染。实验室检查示：ALT222IU／L,AST150IU／L,GGT1124IU／L,TBil22．7umol／L．DBil9．2umol／L。诊断为：药物性肝损害。停药,给予护肝治疗近1个月后肝功能好转,实验室检查：ALT57．2IU／L,AST40．9IU／L,TBil22．3umoL／L,DBil17．8umol／L,GGT344IU／L。     

Automated assessment of the substantia nigra on susceptibility map-weighted imaging using deep convolutional neural networks for diagnosis of Idiopathic Parkinson's disease

ObjectivesDespite its use in determining nigrostriatal degeneration, the lack of a consistent interpretation of nigrosome 1 susceptibility map-weighted imaging (SMwI) limits its generalized applicability. To implement and evaluate a diagnostic algorithm based on convolutional neural networks for interpreting nigrosome 1 SMwI for determining nigrostriatal degeneration in idiopathic Parkinson's disease (IPD).MethodsIn this retrospective study, we enrolled 267 IPD patients and 160 control subjects (125 patients with drug-induced parkinsonism and 35 healthy subjects) at our institute, and 24 IPD patients and 27 control subjects at three other institutes on approval of the local institutional review boards. Dopamine transporter imaging served as the reference standard for the presence or absence of abnormalities of nigrosome 1 on SMwI. Diagnostic performance was compared between visual assessment by an experienced neuroradiologist and the developed deep learning-based diagnostic algorithm in both internal and external datasets using a bootstrapping method with 10000 re-samples by the “pROC” package of R (version 1.16.2).ResultsThe area under the receiver operating characteristics curve (AUC) (95% confidence interval [CI]) per participant by the bootstrap method was not significantly different between visual assessment and the deep learning-based algorithm (internal validation, .9622 [0.8912–1.0000] versus 0.9534 [0.8779-0.9956], P = .1511; external validation, 0.9367 [0.8843-0.9802] versus 0.9208 [0.8634-0.9693], P = .6267), indicative of a comparable performance to visual assessment.ConclusionsOur deep learning-based algorithm for assessing abnormalities of nigrosome 1 on SMwI was found to have a comparable performance to that of an experienced neuroradiologist.     

体外丹酚酸B改善四环素致脂肪肝的作用及机制初探

目的 建立四环素诱导HepG2细胞药物性脂肪肝模型,研究丹酚酸R对此模型的作用,并初步探讨其机制.方法 采用油红O染色观察细胞内脂质积聚情况,采用GPO＆#183;PAP法三酰甘油试剂盒定量检测细胞内三酰甘油的变化及Real-time PCR检测CD36 mRNA的表达.结果 四环素处理后能够明显增强油酸诱导的HepG2细胞脂肪变性（P＜0.05）,同时75 μmol/L四环素处理后显著提高CD36 mRNA的表达（p＜0.05）.丹酚酸B能明显改善四环素油酸诱导的HepG2细胞脂肪积聚,且呈剂量依赖性（P＜0.01）;丹酚酸B高剂量组与造模组相比能显著降低CD36 mRNA的表达（p＜0.05）.结论 丹酚酸B能够改善四环素油酸诱导的HepG2细胞脂肪变性,其作用可能与抑制CD36的表达、影响脂肪酸转运有关.