Abstract：
Autoimmune hepatitis (AIH) is a chronic immune mediated liver disease characterized by elevated transaminases, hyper gammaglobulinemia, presence of autoantibodies and interface hepatitis in the absence of a known etiology of liver disease. Thiopurines (azathioprine [AZA]/6-mercaptopurine [6MP]) and steroids remain the first line of treatment of AIH in both children and adults. However, a small proportion of AIH patients are either non-responders or develop side effects with AZA. The metabolism of AZA is complex and mediated by multiple enzymes. After absorption and getting converted to 6MP, it is converted to 6-thiouric acid, 6-methyl mercaptopurine (6MMP) and 6-thioguanine (6TG) by different enzymes. Elevated 6MMP levels are associated with hepatotoxicity and also poor efficacy due to simultaneous lower levels of 6TG, which is the active drug metabolite related to both efficacy and myelosuppression. Allopurinol, a xanthine oxidase inhibitor shifts the metabolism of AZA away from 6MMP toward 6TG. This combination of allopurinol with reduced dose of AZA is an alternative to more expensive and toxic second line therapy to induce remission in patients with AIH. This article discusses the mechanism of action of allopurinol in inducing response to AZA, reviews the published literature on this combination therapy and gives guidelines on the use of allopurinol in patients with AIH.
摘要：
自身免疫性肝炎(AIH)是一种以转氨酶升高为特征的慢性免疫介导的肝病,高丙种球蛋白血症,在没有已知肝病病因的情况下，存在自身抗体和界面肝炎。硫嘌呤（硫唑嘌呤[AZA]/6-巯基嘌呤[6MP]）和类固醇仍然是儿童和成人AIH的一线治疗方法。然而,一小部分AIH患者要么无应答,要么出现AZA副作用.AZA的代谢是复杂的，由多种酶介导。吸收后转化为6MP，它转化为6-硫代尿酸，6-甲基巯基嘌呤(6MMP)和6-硫代鸟嘌呤(6TG)由不同的酶组成。6MMP水平升高与肝毒性相关，并且由于同时降低6TG而导致疗效不佳。它是与疗效和骨髓抑制有关的活性药物代谢产物。别嘌呤醇,黄嘌呤氧化酶抑制剂使AZA的代谢从6MMP向6TG转移。别嘌呤醇与减少剂量的AZA的这种组合是更昂贵和有毒的二线治疗的替代方案，可诱导AIH患者的缓解。本文讨论了别嘌醇诱导AZA反应的作用机制,回顾了有关该联合治疗的已发表文献,并给出了在AIH患者中使用别嘌呤醇的指南.
