Department of Forensic Medicine, Rennes University Hospital, Rennes, France; IDPSP - EA 4640, Rennes University, Rennes, France.
Department of Forensic Medicine, Rennes University Hospital, Rennes, France; Department of Pathology, Rennes University Hospital, Rennes, France.
Forensic Sci Int. 2020 May;310:110258. doi: 10.1016/j.forsciint.2020.110258. Epub 2020 Mar 17.
Acetaminophen is the leading cause of acute liver failure worldwide following massive ingestion. We present here a fatal acute liver failure after repeated administration of four therapeutic doses of acetaminophen at 4-h intervals in a previously healthy 9-year-old female who presented dental pain after a facial trauma during sport practice. A diagnosis of paracetamol-induced hepatitis was deduced from the clinical picture of fulminant hepatitis and tubular necrosis, the encephalopathy with oedema and without signs of trauma. Liver biopsy showed typical acetaminophen-induced necrosis and a microvesicular steatosis in periportal hepatocytes. These injuries might have been favored by pre-existing mitochondrial dysfunction related, for instance, to a deficiency in an enzyme of the mitochondrial β-oxidation pathway, or the respiratory chain. The observation of microvesicular steatosis in the periportal areas suggests an increased vulnerability via pre-existing mitochondrial dysfunction. As the liver status of patients is mostly unknown, the frequency of administration (every six hours) must be respected and the use of pharmaceutical forms allowing to adjust the dose as closely as possible to the child's weight should be promoted.
对乙酰氨基酚是全球范围内大剂量摄入后导致急性肝衰竭的主要原因。我们在此介绍一例先前健康的 9 岁女性,在运动练习中面部外伤后出现牙痛,每隔 4 小时重复给予四次治疗剂量的对乙酰氨基酚后发生致命性急性肝衰竭。暴发性肝炎和肾小管坏死、伴水肿而无创伤迹象的脑病提示诊断为对乙酰氨基酚引起的肝炎。肝活检显示典型的对乙酰氨基酚诱导性坏死和门脉周围肝细胞微泡性脂肪变性。这些损伤可能与先前存在的线粒体功能障碍有关,例如与线粒体β氧化途径或呼吸链中的酶缺乏有关。门脉周围区域微泡性脂肪变性的观察表明,通过先前存在的线粒体功能障碍,肝脏易感性增加。由于患者的肝脏状况大多未知,必须遵守给药频率(每 6 小时一次),并应推广使用可将剂量尽可能调整至接近儿童体重的药物剂型。