肿瘤坏死因子α抑制剂致药物诱导自身免疫性肝炎的文献分析

Literature analysis of drug-induced autoimmune hepatitis induced by tumor necrosis factor-αinhibitor

目的分析肿瘤坏死因子α抑制剂(TNFi)致药物诱导的自身免疫性肝炎(DIAIH)的特点,为临床安全用药提供参考。方法检索PubMed、Embase、中国学术期刊全文数据库、维普网、万方数据,收集TNFi致DIAIH的病例报道,并进行描述性分析。结果共纳入文献33篇,共涉及患者44例,其中女性31例、男性13例,平均年龄(41.14±2.20)岁,以30~60岁为主(77.27%),原患疾病主要为克罗恩病(CD)、溃疡性结肠炎(UC)和类风湿关节炎(RA)(68.18%)。44例患者中,35例使用英夫利西单抗(IFX),7例使用阿达木单抗,2例使用依那西普;37例患者的用药剂量均在说明书范围内,31例患者合并使用了其他药物;DIAIH的发生时间以用药后≤24周为主(68.18%);21例患者(47.73%)无临床表现;所有患者的丙氨酸转氨酶、天冬氨酸转氨酶水平均异常升高;38例患者的抗核抗体为阳性。除3例患者需进行肝移植术外,其余患者经停药和或给予糖皮质激素等对症治疗后均好转。结论TNFi致DIAIH以女性患者居多,使用常规剂量即可发生,且发生时间差异较大,但不同TNFi致DIAIH后的干预措施基本一致。临床使用TNFi(尤其是IFX)时,应密切关注患者的临床表现、肝功能、自身抗体水平,详细评估以尽早发现DIAIH;若患者的肝功能持续无好转,需尽快停药并进行对症治疗,以避免进展为急重症DIAIH或肝功能衰竭。

OBJECTIVE To analyze the characteristics of drug-induced autoimmune hepatitis(DIAIH)induced by tumor necrosis factor-αinhibitor(TNFi),and to provide reference for clinical drug treatment.METHODS Retrieved from PubMed,Embase,China Academic Journal full-text Database,VIP and Wanfang database,the case reports of TNFi-induced DIAIH were collected to conduct descriptive analysis.RESULTS A total of 33 case reports involving 44 patients were collected,including 31 females and 13 males,with an average age of(41.14±2.20)years old,mostly aged 30 to 60 years(77.27%).The primary diseases were Crohn disease(CD),ulcerative colitis(UC)and rheumatoid arthritis(RA)(68.18%).Of the 44 patients,35 were treated with infliximab(IFX),7 with adalimumab,and 2 with etanercept.The dosage of 37 patients was within the scope of the instructions,and 31 received other drugs additionally;DIAIH mainly occurred≤24 weeks after medication(68.18%);21 patients(47.73%)had no clinical manifestations;alanine aminotransferase and aspartate aminotransferase were abnormally elevated in all patients;anti-nuclear antibodies were positive in 38 patients.Except for 3 patients who required liver transplantation,all the other patients improved after drug withdrawal and/or symptomatic treatment such as glucocorticoid therapy.CONCLUSIONS TNFiinduced DIAIH is more common in female patients and can occur with conventional doses,with significant differences in occurrence time.However,the intervention measures are basically the same for DIAIH induced by different types of TNFi.Clinical use of TNFi,especially the use of IFX,requires close attention to the clinical manifestations,liver function and autoantibody level,and a detailed evaluation should be conducted to detect DIAIH as soon as possible.If liver function continues to not improve,it is necessary to stop taking medicine as soon as possible and receive symptomatic treatment to avoid developing acute or severe DIAIH or liver failure.