Nottingham Digestive Diseases Centre, National Institute of Health Research Biomedical Research Unit, Nottingham University Hospitals NHS Trust, Queen's Medical Centre, Derby Road, Nottingham, UK.
Nat Rev Rheumatol. 2011 Mar;7(3):139-50. doi: 10.1038/nrrheum.2010.214. Epub 2011 Jan 25.
Antirheumatic agents are among commonly used drugs associated with adverse hepatic reactions. Sulfasalazine and azathioprine are among the most important causes of acute hepatotoxicity. Because such a large number of people take NSAIDs, even the rare occurrence of hepatotoxicity from these agents might contribute substantially to the total burden of drug-induced liver disease. A wide spectrum of hepatotoxic effects is described with antirheumatic drugs. Studies investigating genetic susceptibility to diclofenac hepatotoxicity have expanded our understanding of the potential drug-specific, class-specific and general factors involved in its pathogenesis, and methotrexate-associated liver disease demonstrates the interaction between drug, host and environmental factors that determines the likelihood and magnitude of liver disease. Infliximab therapy is associated with typical drug-induced autoimmune hepatitis. Although validated causality assessment methods have been used to objectively assess the strength of the association between a drug and a clinical event, in practice the diagnosis of drug-induced liver injury (DILI) involves a clinical index of suspicion, pattern recognition, the establishment of a temporal relationship between drug exposure and the adverse event, and the exclusion of alternative explanations for the clinical presentation. Detailed understanding of genetic and environmental factors underlying an individual's susceptibility would enable risk reduction and potentially primary prevention of hepatotoxicity.
抗风湿药是与肝不良反应相关的常用药物之一。柳氮磺胺吡啶和硫唑嘌呤是引起急性肝毒性的最重要原因之一。由于有大量的人在服用 NSAIDs,即使这些药物引起肝毒性的情况很少,也可能会对药物性肝疾病的总负担产生重大影响。抗风湿药物可引起广泛的肝毒性作用。研究表明,对双氯芬酸肝毒性的遗传易感性的研究,扩展了我们对发病机制中涉及的潜在药物特异性、类别特异性和一般因素的理解,而甲氨蝶呤相关的肝病则表明药物、宿主和环境因素之间的相互作用决定了肝病的可能性和严重程度。英夫利昔单抗治疗与典型的药物诱导的自身免疫性肝炎有关。虽然已经使用经过验证的因果关系评估方法来客观评估药物与临床事件之间的关联强度,但实际上,药物性肝损伤(DILI)的诊断涉及对临床可疑性、模式识别、药物暴露与不良事件之间的时间关系的建立,以及对临床表现的其他解释的排除。详细了解个体易感性的遗传和环境因素将能够降低肝毒性的风险,并有可能进行原发性预防。