Farrell G C
Storr Liver Unit, University of Sydney at Westmead Hospital, NSW, Australia.
J Gastroenterol Hepatol. 1997 Oct;12(9-10):S242-50. doi: 10.1111/j.1440-1746.1997.tb00507.x.
Drugs and other chemical toxins account for less than 5% of cases of jaundice or acute hepatitis and fewer cases of chronic liver disease, but they are an important cause of more severe types of hepatic injury. Drug reactions produce an array of hepatic lesions that mimic all known hepatobiliary diseases; this poses a diagnostic challenge for physicians and pathologists. Diagnosis of drug-induced hepatic injury is circumstantial, with positive rechallenge being the only factor that unequivocally implicates a particular agent. Nonetheless, other aspects of the temporal relationship between drug ingestion and adverse reaction, exclusion of other diseases, the presence of extrahepatic features of drug hypersensitivity and some findings on liver biopsy can lend support to the diagnosis. Some of these issues will be explored in this review by considering contemporary paradigms of drug-induced hepatic injury. Factors that predispose to dose-dependent hepatic injury will be considered in relation to acetaminophen, an example of acute hepatotoxicity, and methotrexate, an agent that can produce hepatic fibrosis. Flucloxacillin will be discussed as an example of drug-induced cholestatic hepatitis often associated with prolonged cholestasis and the vanishing bile duct syndrome. Minocycline and diclofenac will be mentioned as two drugs for which drug hepatitis is an exceedingly rare complication. Finally, the evidence that Chinese herbal medicines can be hepatotoxic will be reviewed.
药物和其他化学毒素导致的黄疸或急性肝炎病例不到5%，导致的慢性肝病病例更少，但它们是更严重类型肝损伤的重要原因。药物反应会产生一系列肝脏病变，这些病变可模仿所有已知的肝胆疾病；这给医生和病理学家带来了诊断挑战。药物性肝损伤的诊断是基于间接证据的，再次用药阳性是唯一能明确表明某一特定药物致病的因素。尽管如此，药物摄入与不良反应之间的时间关系的其他方面、排除其他疾病、药物超敏反应的肝外特征的存在以及肝活检的一些发现都可为诊断提供支持。在本综述中，将通过考虑药物性肝损伤的当代范例来探讨其中的一些问题。将结合对乙酰氨基酚（急性肝毒性的一个例子）和甲氨蝶呤（一种可导致肝纤维化的药物）来考虑易导致剂量依赖性肝损伤的因素。氟氯西林将作为药物性胆汁淤积性肝炎的一个例子进行讨论，这种肝炎常与长期胆汁淤积和胆管消失综合征相关。米诺环素和双氯芬酸将作为药物性肝炎极为罕见并发症的两种药物被提及。最后，将综述中草药具有肝毒性的证据。
