免疫抑制剂相关肝损伤的发生率、临床表现、发生机制与防治建议

Incidence,clinicalfeatures,mechanism and prevention of immunosuppressive agents-related liver injury

免疫抑制剂(immunosuppressive agents,ISA)是一类具有抑制机体免疫反应作用的药物,临床主要用于治疗移植后的免疫排斥反应和自身免疫性疾病。肝毒性是ISA常见的药物不良反应之一,严重时可发展为肝衰竭甚至死亡。然而,目前关于ISA相关肝损伤的临床证据大多局限于小样本量回顾性研究和零散的病例报道,其发生率、临床表现和发生机制尚不明确。该文拟对常见的小分子ISA(甲氨蝶呤、环磷酰胺、硫唑嘌呤、吗替麦考酚酯、来氟米特、环孢素A、他克莫司、西罗莫司和依维莫司等)相关肝损伤的发生率、临床表现、发生机制和防治建议进行综述,以期为临床合理用药提供理论依据,降低ISA药物不良反应发生率,提高患者预后质量。

Immunosuppressive agents(ISA)are a class of drugs that inhibit immune response of body,which are mainly used for preventing allograft rejection post-transplantation and the treatment of autoimmune disease.Hepatotoxicity is one of the common adverse drug reactions,which can lead to liver failure and even death in severe cases.However,the clinical evidence of ISA-related liver injury is limited.This review describes the incidences,clinical features,mechanisms,managements and preventions of drug-induced liver injury caused by common small molecule ISA(including methotrexate,cyclophosphamide,azathioprine,mycophenolate mofetil,leflunomide,cyclosporine A,tacrolimus,sirolimus and everlimus),providing reference for the clinical rational drug use of ISA.