MICA: Point-of-care assessment of drug-induced liver injury (POC-DILI)

服用过量的扑热息痛是很常见的。英国每年约有10万例过量服用药物的病例在急诊室就诊。其中，大约一半需要用解毒剂进行紧急治疗，以防止肝损伤。在英国，需要治疗的患者数量与另一种非常常见的医疗紧急情况--髋关节骨折的人数相似。在英国，扑热息痛直接导致每年100-150人死亡，主要是年轻人，无显著合并症。扑热息痛的解毒剂叫乙酰半胱氨酸。它的用途：（i）只有在服用过量后约8小时内给药才完全有效。如果治疗延迟超过20小时，则无效。因此，在有肝损伤风险的患者中，必须尽快开始治疗（ii）药物不良反应（ADR）：超过一半的接受者发生恶心/呕吐，约三分之一发生过敏反应。(iii)持续时间长：该方案耗时，至少需要21小时才能完成，导致大量医院病床占用。医生用于确定哪些患者需要乙酰半胱氨酸治疗的血液测试目前并不理想。在这个项目中，我们将开发一种新的测试，将快速识别对乙酰氨基酚过量后需要治疗的患者。我们的新测试的主要优点是：1.当患者第一次到达医院时，我们将测量的肝损伤标志物（细胞角蛋白-18，（K18））比目前的测试更敏感，这意味着医生可以更快地发现肝损伤，并在需要的患者中及时开始治疗。2.我们的分析是快速的（时间20分钟）3。我们的检测方法是用手指刺血，而不需要静脉采血。该检测是即时检测，这意味着检测是在急诊室完成的，而不是送到医院实验室。这加快了过程，并消除了血液样本丢失的风险。5.该检测试剂盒价格低廉，这意味着它可以广泛使用，包括在低收入和中等收入国家。在本项目中，我们将开发我们的K18检测试剂盒，然后在急诊科进行概念验证临床研究，以确定我们独特的解决方案对常见但被忽视的临床问题的准确性。

Taking an overdose of paracetamol is very common. There are around 100,000 cases of overdose that attend Emergency Departments in the UK every year. Of these, around half need emergency treatment with an antidote to prevent liver damage. The number of patients needing treatment in the UK is similar to the number of people who break their hips, another very common medical emergency. Paracetamol is directly responsible for the deaths of 100-150 people per year in the UK, predominately young people with no significant co-morbidity. The antidote to paracetamol is called acetylcysteine. There are problems with its use: (i) it is only fully effective when administered within around 8 h of taking the overdose. It is ineffective if treatment is delayed more than about 20 h. Therefore, treatment must be started as quickly as possible in those patients at risk of liver damage (ii) Adverse drug reactions (ADRs): nausea/vomiting occurs in more than half of recipients and allergic reactions in about a third. (iii) Prolonged duration: The regime is time consuming, taking at least 21 h to complete, leading to significant hospital bed occupancy. The blood tests used by doctors to identify which patients need treatment with acetylcysteine are currently not optimal. In this project we will develop a new test that will rapidly identify patients who need treatment following paracetamol overdose. The key advantages of our new test are:1. The marker of liver damage we will measure (cytokeratin-18, (K18)) is more sensitive than the current tests when the patient first arrives at hospital meaning doctors can pick up liver damage more quickly and start treatment promptly in those patients who need it. 2. Our assay is rapid (time to result 20 minutes)3. Our assay works with a finger prick of blood rather than needing blood from a vein.4. The assay is point of care which means the test is done in the Emergency Department rather than being sent to the hospital lab. This speeds up the process and eliminates the risk of blood samples being lost. 5. The assay is cheap, which means it can be used widely, including in low and middle income countries.In this project we will develop our K18 assay then perform a proof-of-concept clinical study in Emergency Departments to determine the accuracy of our unique solution to a common, but neglected, clinical problem.