Antituberculous drug-induced liver injury: current perspective.
Antituberculous drug-induced liver injury: current perspective.
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发表时间：
2011-11
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通讯作者：
H. Devarbhavi
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作者：
H. Devarbhavi
药物性肝损伤（DILI）是所有地区肝损伤的一个轻微但重要的原因。在印度和许多发展中国家，抗结核药物性肝损伤（TB DILI）是DILI和药物性急性肝衰竭（DIALF）的主要原因。DILI的单中心登记继续强调DILI和DIALF的高发病率，其中大部分是由于诊断错误和不适当的处方。临床谱包括肝检查无症状升高到急性肝炎和急性肝衰竭。结核病DILI可发生在所有年龄组，包括具有显著发病率和死亡率的儿童。虽然TB DILI在男性中更为常见，但ALF在女性中更为常见，预后较差。关于遗传因素和环境因素作用的对比报告继续发表。由于DILI是一种排除诊断，在这种情况下需要排除急性病毒性肝炎，特别是戊型肝炎。黄疸、低白蛋白血症、腹水、脑病和凝血酶原时间高是不良预后指标。最近关于n -乙酰半胱氨酸在老年人DIALF和预防TB DILI中的有益作用的报道需要进一步调查。重新引入抗结核治疗必须与适应知识相平衡，适应是抗结核药物的常见现象。尽管监测和再挑战的做法差别很大，但早期临床症状的重要性不可低估。联合用药或序贯治疗的同时再激尿DILI发生率相似，尽管关于吡嗪酰胺在DILI和再激尿中的作用的报道越来越多，需要谨慎使用。艾滋病毒或慢性乙型或丙型肝炎和结核病的联合痛苦带来了多重挑战，包括DILI风险大大增加。
Drug-induced liver injury (DILI) is a minor but significant cause of liver injury across all regions. Antituberculosis drug-induced liver injury (TB DILI) is a leading cause of DILI and drug-induced acute liver failure (DIALF) in India and much of the developing world. Single center registries of DILI continue to highlight the high incidence of DILI and DIALF, much of it due to diagnostic errors and inappropriate prescriptions. The clinical spectrum includes asymptomatic elevation in liver tests to acute hepatitis and acute liver failure. TB DILI can occur across all age groups including children with significant morbidity and mortality. Although TB DILI develops more commonly in males, ALF is noted to be commoner in females with a worse prognosis. Contrasting reports on the role of genetic and environmental factors continue to be published. Since DILI is a diagnosis of exclusion, acute viral hepatitis particularly hepatitis E needs to be excluded in such cases. The presence of jaundice, hypoalbuminemia, ascites, encephalopathy and high prothrombin time are poor prognostic markers. Recent reports of the beneficial role of N-acetylcysteine in DIALF and in preventing TB DILI in elderly individuals needs further investigation. Reintroduction of antitubercular therapy must be balanced with the knowledge of adaptation a common occurrence with antituberculosis drugs. Although monitoring and rechallenge practices vary greatly, the importance of early clinical symptoms cannot be underestimated. Simultaneous rechallenge with combination drugs or sequential treatment have similar incidence of DILI, although increasing reports about the role of pyrazinamide in DILI and on rechallenge warrants its careful use. The combined affliction of HIV or chronic hepatitis B or C and tuberculosis poses multiple challenges including the greatly increased risks of DILI.