药物诱导的自身免疫性肝炎49例临床特征分析

Clinical characteristics of drug-induced autoimmune hepatitis

目的探讨药物诱导的自身免疫性肝炎(DIAIH)的临床特征,以期提高临床医生对DIAIH的认识及诊断水平。方法回顾性分析2013年1月至2017年12月在中国医科大学附属盛京医院就诊的DIAIH和药物性肝损伤(DILI)患者。比较两组患者人口学特征、主要诱发药物、临床表现、生化学、自身免疫抗体、肝组织病理学特点。结果共有49例DIAIH患者和436例DILI患者,DIAIH和DILI患者均以女性为主,分别占91.84%(45/49)和70.41%(307/436),DIAIH女性患者的比例显著高于DILI女性患者的比例(χ~2=9.111,P=0.003)。DIAIH患者的平均年龄(50.0±7.4)岁。引起DIAIH的前三位药物分别是中草药(53.06%,26/49)、非甾体抗炎药(10.20%,5/49)和他汀类药物(10.20%,5/49),DIAIH发生的时间均在用药后8周以上。DILI和DIAIH发生肝衰竭的比例分别是14.68%(64/436)和30.61%(15/49),DIAIH较DILI患者更容易发生肝衰竭(χ~2=8.20,P=0.004)。西药引起DIAIH和DILI进展为肝衰竭的风险均显著高于中药(χ~2=9.77,P=0.002;χ~2=16.09,P<0.001)。DIAIH患者的自身免疫抗体阳性率是100%,ANA阳性率83.67%(41/49),SMA阳性率16.33%(8/49)。DIAIH界面性炎症、浆细胞和淋巴细胞浸润均较DILI明显。结论女性更容易发生DIAIH,中草药易引起DIAIH,西药引起的DIAIH易发生肝衰竭。

Objective To investigate the clinical characteristics of drug-induced autoimmune hepatitis(DIAIH),in order to help clinicians learn more about DIAIH and improve its clinical diagnosis.Methods This was a retrospective study in the patients with DIAIH and DILI treated at Shengjing Hospital of China Medical University between January 2013 and December 2017.The population characteristic,related drugs,clinical manifestations,liver biochemical parameters,autoimmune antibodies,and liver pathological features were compared between the two groups.Results There were 49 patiens with DIAIH and 436 patiens with DILI.The majority of these patients were female.There was a significant difference in the proportion of female patients,with DIAIH(91.84%,45/49)higher than DILI(70.41%,307/436)(χ~2=9.111,P=0.003).The patients with DIAIH had a mean age of(50.0±7.4)years.The top three drugs inducing DIAIH were Chinese herbal medicines(53.06%,26/49),non-steroidal anti-inflammatory drugs(10.20%,5/49)and fluvastatin(10.20%,5/49).DIAIH occurred after more than 8 weeks of treatment.There was a significant difference in the proportion of liver failure,with DIAIH(30.61%,15/49)higher than DILI(14.68%,64/436)(χ~2=8.20,P=0.004).The risks of DIAIH and DILI with liver failure caused by western medicines were significantly higher than those by Chinese herbal medicines(χ~2=9.77,P=0.002;χ~2=16.09,P<0.001).The positive rate of autoimmune antibody in DIAIH patients was 100%.The positive rate of ANA was 83.67%(41/49),and that of SMA was 16.33%(8/49).The liver pathological features of interface hepatitis,plasma cells and lymphocytes infiltration in DIAIH patients were more obvious than those in DILI patients.Conclusion DIAIH is more common in the female patients and is caused frequently by Chinese herbal medicines.DIAIH caused by western medicines could easily result in liver failure.