中草药与西药致药物性肝损伤的临床特征及其预后的对比研究

A comparison study of clinical features and prognosis between herbal and dietary supplements and Western medicine induced liver injuries

目的对比中草药或保健品与西药致药物性肝损伤(drug-induced liver injury,DILI)的临床特征及其预后。方法回顾分析2009年1月至2019年1月首都医科大学附属北京友谊医院肝病中心住院的DILI患者临床数据。根据致肝损伤药物种类,分为中草药或保健品组、西药组和中西药联合组(即同时服用中草药或保健品+西药)。比较3组患者的人口学特征、临床症状、肝损伤类型、肝脏生化、免疫球蛋白水平及临床转归异同。连续变量采用ANOVA检验或非参数检验,分类变量采用卡方检验,多重比较采用Bonferroni校正。结果共纳入596例DILI患者。中草药或保健品组348例(58.4%)、西药组137例(23.0%)、中西药联合组111例(18.6%)。中草药或保健品组药物组成以保健、骨关节系统、消化系统、皮肤系统用药最多,占总数的62.6%;西药组以抗生素及抗真菌药物、心血管系统用药、非甾体类抗炎药(nonsteroidal anti-inflammatory drugs,NSAIDs)最多,占68.6%;中西药联合组以中草药或保健品联合抗生素或NSAIDs最多,占75.7%。中草药或保健品组、中西药联合组、西药组,肝细胞损伤型分别为288例(82.8%)、85例(76.6%),98例(71.5%)、混合型及胆汁淤积型分别为60例(17.3%)、26例(23.4%)、39例(28.4%),差异有统计学意义(χ^(2)=10.092,P=0.039)。中草药或保健品组ALT、AST高于西药组,碱性磷酸酶(alkaline phosphatase,ALP)、谷氨酰转肽酶(glutamyl transpeptidase,GGT)低于西药组。中草药或保健品组、中西药联合组、西药组ALT分别为688.4(420,1156.0)U/L、694.3(348.5,1010.8)U/L、495.0(300.0,926.0)U/L,(F=13.681,P=0.001);AST分别为507.5(216.0,822.0)U/L、467.5(158.8,794.7)U/L、325.5(187.0,677.2)U/L,(F=8.912,P=0.012);ALP分别为172.0(123.3,235.3)U/L、188.0(144.6,276.3)U/L、186.0(141.0,349.3)U/L,(F=8.801,P=0.012);GGT分别为209.0(119.0,350.5)U/L、219.0(146.5,367.5)U/L、289.0(136.8,519.8)U/L,(F=10.945,P=0.004)。3组严重程度(χ^(2)=1.841,P=0.986)和临床结局(χ^(2)=6.135,P=0.408)比较差异无统计学意义。结论中药致肝损伤以保健、骨关节、消化及皮肤系统用药最多见;西药以抗微生物药、心血管系统药、NSAIDs最多见;中西药联合组以中草药联合抗微生物药、NSAID最多见。与西药相比,中草药或保健品肝细胞损伤型比例更高,患者的ALT、AST升高,ALP、GGT降低;临床结局无显著差异。

Objective To explore the similarities and differences of clinical characteristics between the liver injuries induced by herbal and dietary supplements(HDS)and by Western medicine.Methods The clinical data of 596 patients with drug-induced liver injuries(DILI)who were hospitalized in Beijing Friendship Hospital,Capital Medical University from January 2009 to January 2019 were retrospectively analyzed.According to the types of drugs to induce liver injuries,the patients were divided into(1)HDS group(N=348,58.4%);(2)Western medicine group(N=137,23.0%);(3)Combination group(i.e.,taking HDS and western medicine simultaneously)(N=111,18.6%).The demographic characteristics,clinical presentation,types of liver injuries,liver biochemistries,immunoglobulin levels and clinical outcomes of patients in different groups were compared.Analysis of Variance(ANOVA)test or nonparametric tests were used for continuous variables,and Chi Square test was used for categorical variables.Bonferroni correction was used for multiple comparisons.P<0.05 was considered statistically significant.Results The top four categories of drugs to cause DILI in HDS group were health build-up products,herbs for the treatment of osteoarticular diseases,digestive and skin diseases,accounted for 62.6%in total.The top four categories drugs to cause DILI in western medicine group were antibiotics and antifungal drugs,cardiovascular system drugs,antipyretic and nonsteroidal anti-inflammatory drugs(NSAIDs),accounting for 68.6%.The most common western drugs to induce DILI in combination group were antibiotics and NSAIDs plus herbal medicine,accounting for 75.7%.The proportions of hepatocelluar injury type decreased{288(82.8%),85(76.6%),98(71.5%),respectively},whereas those of mixed and cholestatic types increased{60(17.3%),26(23.4%),39(28.4%),respectively}significantly in HDS,combination and western medicine group(P=0.039).The peak levels of alanine transaminase(ALT)and aspartate transaminase(AST)of HDS group were significantly higher,whereas the peak levels of alkaline phosphatase(ALP)and glutamyl transpeptidase(GGT)were significantly lower than those of western medicine group.The peak levels of ALT,AST,ALP,and GGT in HDS,combination group and western medicine group were 688.4(420.0,1156.0)U/L,694.3(348.5,1010.8)U/L,495.0(300.3,926.0)U/L for ALT(P=0.001);507.5(261.0,822.0)U/L,467.5(158.8,794.7)U/L,325.5(187.0,677.2)U/L for AST(P=0.001);172.0(123.3,235.3)U/L,188.0(144.6,276.3)U/L,186.0(141.0,349.3)U/L for ALP(P=0.012);and 209.0(119.0,350.5)U/L,219.0(146.5,367.5)U/L,289.0(136.8,519.8)U/L for GGT(P=0.004),respectively.The severity(P=0.986)and clinical outcomes(P=0.408)of these three groups were similar.Conclusion The top 4 categories drugs to induce liver injuries for HDS were health build-up products,drugs for the treatment of osteoarticular diseases,digestive and skin diseases.The top 3 western medicine categories to induce liver injuries included antimicrobial/antifungal drugs,cardiovascular system drugs and NSAIDs.HDS combined with NSAIDs or antibiotics were the most common combination drugs to induce liver injuries.There is no significant difference in severity and outcomes between HDS and western drugs.