异甘草酸镁治疗自身免疫样药物性肝损伤的效果和安全性

Clinical effect and safety of magnesium isoglycyrrhizinate in treatment of autoimmune-like drug-induced liver injury

目的探索异甘草酸镁治疗自身免疫样药物性肝损伤的临床疗效和安全性。方法选取首都医科大学附属北京佑安医院2016年7月-2019年1月住院的自身免疫样药物性肝损伤患者53例为观察组,另选不伴有自身免疫现象的药物性肝损伤患者50例为对照组。所有患者给予异甘草酸镁200 mg/d,治疗4周。观察治疗前后患者肝功能情况,观察治疗前后观察组患者的免疫学指标,记录两组患者的不良反应。治疗结束后每月随访肝功能,随访时间6个月。正态分布计量资料组间比较采用t检验,非正态分布的计量资料采用Mann-Whitney U检验,计数资料组间比较采用χ^2检验或Fisher精确概率检验。结果观察组治疗后与治疗前比较,ALT[35.4(29.2~42.0)U/L vs 289.0(226.6~460.3)U/L,Z=-8.661,P<0.001]、AST[46.3(15.6~183.5)U/L vs 306.3(32.2~589.8)U/L,Z=-5.271,P<0.001]、GGT[77.0(53.2~183.2)U/L vs 129.0(77.8~232.5)U/L,Z=-3.437,P=0.001)]、ALP[83.1(64.9~83.1U/L vs 119.4(104.9~146.9)U/L,Z=-3.485,P<0.001]和TBil[(27.5±10.3)μmol/L vs(59.7±18.6)μmol/L,t=6.673,P<0.001]水平均明显降低;对照组患者治疗后与治疗前比较,ALT[33.1(14.9~106.4)U/L vs 300.6(206.8~679.5)U/L,Z=-8.232,P<0.001]、AST[44.1(20.8~151.6)U/L vs 321.7(36.2~553.2)U/L,Z=-3.549,P<0.001]、GGT[82.7(50.6~168.5)U/L vs 133.5(72.2~254.2)U/L,Z=-2.364,P=0.018]、ALP[87.6(74.3~139.4)U/L vs 128.0(106.3~201.4)U/L,Z=-4.303,P<0.001]和TBil[(23.8±10.9)μmol/L vs(58.3±19.8)μmol/L,t=-8.450,P<0.001]水平也明显降低。但治疗后两组间比较差异均无统计学意义(P值均>0.05)。治疗后观察组患者IgG水平由(15.8±3.2)g/L降至(14.2±2.0)g/L,治疗前IgG水平升高(>16 g/L)患者22例中18例(81.8%)恢复正常。36例ANA阳性患者19例(52.7%)阴转。两组患者均无严重不良反应。行肝穿病理检查患者中,观察组患者中性粒细胞和(或)嗜酸性粒细胞浸润(17/32,53.1%)明显高于对照组(3/17,17.5%)(χ^2=5.785,P=0.016)。结论异甘草酸镁用于治疗自身免疫样药物性肝损伤安全有效,是临床治疗的可选择方案。

Objective To investigate the clinical effect and safety of magnesium isoglycyrrhizinate in the treatment of autoimmune-like drug-induced liver injury.Methods A total of 53 patients with autoimmune-like drug-induced liver injury who were hospitalized in Beijing YouAn Hospital,Capital Medical University,from July 2016 to January 2019 was enrolled as observation group,and 50 patients with drug-induced liver injury who had no autoimmune symptoms were enrolled as control group.All patients were given magnesium isoglycyrrhizinate(200 mg/d)for 4 weeks.Liver function and immunological indices were observed before and after treatment,and adverse reactions were recorded for all patients.Liver function was followed up every month for 6 months after treatment.The t-test was used for comparison of normally distributed continuous data between groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups;the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups.Results After treatment,the observation group had significant reductions in alanine aminotransferase(ALT)[35.4(29.2-42.0)U/L vs 289.0(226.6-460.3)U/L,Z=-8.661,P<0.001],aspartate aminotransferase(AST)[46.3(15.6-183.5)U/L vs 306.3(32.2-589.8)U/L,Z=-5.271,P<0.001],gamma-glutamyl transpeptidase(GGT)[77.0(53.2-183.2)U/L vs 129.0(77.8-232.5)U/L,Z=-3.437,P=0.001],alkaline phosphatase(ALP)[83.1(64.9-83.1)U/L vs 119.4(104.9-146.9)U/L,Z=-3.485,P<0.001],and total bilirubin(TBil)(27.5±10.3μmol/L vs 59.7±18.6μmol/L,t=6.673,P<0.001),and the control group also had significant reductions in ALT[33.1(14.9-106.4)U/L vs 300.6(206.8-679.5)U/L,Z=-8.232,P<0.001],AST[44.1(20.8-151.6)U/L vs 321.7(36.2-553.2)U/L,Z=-3.549,P<0.001],GGT[82.7(50.6-168.5)U/L vs 133.5(72.2-254.2)U/L,Z=-2.364,P=0.018],ALP[87.6(74.3-139.4)U/L vs 128.0(106.3-201.4)U/L,Z=-4.303,P<0.001],and TBil(23.8±10.9μmol/L vs 58.3±19.8μmol/L,t=-8.450,P<0.001);however,there were no significant differences between the two groups after treatment(P>0.05).For the observation group,the level of IgG decreased from 15.8±3.2 g/L before treatment to 14.2±2.0 g/L after treatment,and among the 22 patients with elevated IgG(>16 g/L)before treatment,18(81.8%)had an IgG level back to normal.Among the 36 patients with positive anti-nuclear antibody,19(52.7%)achieved negative conversion.No serious adverse reaction was observed in the two groups.In terms of the patients who underwent liver biopsy,the observation group had a significantly higher proportion of patients with neutrophil and/or eosinophil infiltration than the control group[53.1%(17/32)vs 17.5%(3/17),χ^2=5.785,P=0.016].Conclusion Magnesium glycyrrhizinate is safe and effective in the treatment of autoimmune-like drug-induced liver injury and can thus be selected as an alternative treatment method in clinical practice.