儿科药物性肝损伤:简要综述

M. Tei, F. Lotti, Flavio Storelli, S. Grosso
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摘要

药物性肝损伤(DILI)是一种未被充分认识的儿科肝病病因。尽管儿童DILI约占所有年龄组报告的所有药物不良反应的1%,占所有临床DILI病例的不到10%,但它导致了约20%的急性肝衰竭(ALF)病例。广泛的药物、草药产品和营养补充剂通过剂量依赖性、特异性或间接机制与DILI的发生有关。有限的文献可用于儿科人群,使DILI仍然是一个具有挑战性的诊断。准确的病史至关重要,并应调查药物使用情况、临床和实验室结果、药物相关副作用或合并症的个人和家庭危险因素、开始使用相关药物后损伤发生的时间(潜伏期)。DILI的临床表现从无症状或非常轻微到严重,有时甚至致命;实验室检查可能有助于排除肝损伤的其他原因,但除了少数例外,它们是特定的。早期怀疑和迅速停用药物对大多数病例的成功管理起着关键作用。很少有特定的治疗方法,如对乙酰氨基酚毒性,用n -乙酰半胱氨酸治疗,丙戊酸钠毒性,左旋肉碱可能有益。虽然还没有对照试验,但如果停药后没有改善,可以考虑使用皮质类固醇和熊去氧胆酸。这篇简短的综述并不打算涉及DILI的所有方面,而是侧重于流行病学、发病机制、临床特征、实际管理和儿科年龄的当前挑战。
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Drug-Induced Liver Injury in Paediatrics: A Short Review
Drug-induced liver injury (DILI) is an under-recognized cause of paediatric liver disease. Although DILI in children accounts for about 1% of all reported adverse drug reactions throughout all age groups and less than 10% of all clinical DILI cases, it is responsible for about 20% of acute liver failure (ALF) cases. A wide range of drugs, herbal products and nutritional supplements have been associated with the development of DILI through dose-dependent, idiosyncratic or indirect mechanism. Limited literature is available in pediatric population, making DILI a still challenging diagnosis. An accurate medical history is of pivotal importance and should investigate about drug consumption, clinical and laboratory findings, individual and family risk factors for drug-related side effects or comorbidities, the timing of the injury onset after the implicated agent has been started (latency). Clinical presentation of DILI varies from asymptomatic or very mild to serious and sometimes fatal conditions; laboratory tests may be helpful in ruling out other causes of liver injury but, with few exceptions, they are aspecific. Early suspicion and prompt withdrawal of the offending drug play a key role for a successful management of most cases. Rarely a specific therapy is available, as for acetaminophen toxicity, treated with N-acetylcysteine, and sodium valproate toxicity, where carnitine may be beneficial. Although controlled trials are not available yet, corticosteroids and ursodeoxycholic acid can be considered if no improvement is proven after discontinuation of drug. The present short review is not intended to deal with all aspects concerning DILI but to focus on epidemiology, pathogenesis, clinical features, practical management and current challenges in paediatric age.
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