药物诱导性自身免疫性肝炎与药物性肝损伤和自身免疫性肝炎患者临床特征比较研究

Comparison of clinical features of patients with drug-induced autoimmune hepatitis,autoimmune hepatitis and drug-induced liver injury

目的分析比较药物诱导性自身免疫性肝炎(DI-AIH)、药物性肝损伤(DILI)和自身免疫性肝炎(AIH)患者的临床特征。方法2017年1月~2021年12月我院收治的22例DI-AIH患者、23例DILI患者和23例AIH患者,给予DI-AIH和AIH患者泼尼松或/和硫唑嘌呤联合治疗,给予DILI患者丁二磺酸腺苷蛋氨酸联合异甘草酸镁注射液治疗,直至肝功能指标正常,随访24个月。结果DILI组和DI-AIH组明确应用药物百分比分别为82.6%和100.0%,均显著高于AIH组的17.4%(P<0.05),且均以应用中草药为主;三组常见的临床症状为食欲下降、眼黄、腹泻等,且三组临床症状发生率存在显著性差异(DI-AIH、AIH和DILI组分别为81.8%、52.2%和47.8%,P<0.05);DI-AIH组血清ALT、ALP、GGT和总胆汁酸水平分别为331.2(116.4,512.5)U/L、125.4(91.6,164.8)U/L、202.4(98.8,394.1)U/L和23.7(13.1,69.7)μmol/L,显著高于DILI组【分别为198.6(94.3,497.6)U/L、98.9(67.7,168.9)U/L、101.2(49.6,231.4)U/L和7.1(2.7,29.2)μmol/L,P<0.05】或AIH组【分别为86.7(32.4,186.3)U/L、65.8(54.7,109.8)U/L、71.6(61.4,142.5)U/L和11.5(4.1,35.6)μmol/L,P<0.05】,而AIH组血清球蛋白水平为35.6(28.7,41.4)g/L,显著高于DILI组【28.8(21.2,34.5)g/L,P<0.05】或DI-AIH组【30.5(24.6,42.1)g/L,P<0.05】;三组白细胞计数比较差异均无统计学意义(P>0.05)。结论DILI和DI-AIH的致病药物主要以中草药应用为主,DI-AIH患者存在一些较特殊的临床特征值得关注,表现为血清酶学水平较高,对免疫抑制和护肝治疗有效。

Objective The aim of this study was conducted to compare the clinical features of patients with drug-induced autoimmune hepatitis(DI-AIH),autoimmune hepatitis(AIH)and drug-induced liver injury(DILI).Methods 22 patients with DI-AIH,23 patients with DILI and 23 patients with AIH were encountered in our hospital between January 2017 and December 2021,the patients with AIH and DI-AIH were treated with prednisone and/or azathioprine combination therapy,and those with DILI were dealt with liver-protecting medicines.All patients were followed-up for two years.Results The percentages of definite medicine administered before diagnosis of patients with DILI and DI-AIH were 82.6%and 100.0%,with the alleged Chinese herbal medicine mainly,both significantly higher than 17.4%(P<0.05)in patients with AIH;the incidence of common symptoms,such as anorexia,jaundice and diarrhea in patients with DI-AIH was 81.8%,much higher than 52.2%and 47.8%(P<0.05)in those with AIH or with DILI;serum alanine aminotransaminase,alkaline phosphatase,glutamine transpeptidase and total bile acid levels in patients with DI-AIH were 331.2(116.4,512.5)U/L,125.4(91.6,164.8)U/L,202.4(98.8,394.1)U/L and 23.7(13.1,69.7)μmol/L,all significantly higher than[198.6(94.3,497.6)U/L,98.9(67.7,168.9)U/L,101.2(49.6,231.4)U/L and 7.1(2.7,29.2)μmol/L,respectively,P<0.05]in patients with DILI or[86.7(32.4,186.3)U/L,65.8(54.7,109.8)U/L,71.6(61.4,142.5)U/L and 11.5(4.1,35.6)μmol/L,respectively,P<0.05]in patients with AIH,while serum globulin level in patients with AIH was 35.6(28.7,41.4)g/L,significantly higher than 28.8(21.2,34.5)g/L in patients with DILI(P<0.05)or 30.5(24.6,42.1)g/L in patients with DI-AIH(P<0.05);there were no significant differences as respect to peripheral white blood cell counts among the three groups(P>0.05).Conclusion The main pathogenic medicines in patients with DILI and DI-AIH are Chinese herbal medicine,and the clinical features of patients with DI-AIH are unique,presenting with highly increased serum biochemical parameters and good prognosis,showing response to immunosuppression and liver-protecting therapy.