Clinical Characteristics And Risk Factors Of Drug-induced Liver Injury Caused By Traditional Chinese Medicine: A Systematic Evaluation Study

Purpose: A systematic review aimed to evaluate the characteristics,clinical presentations,risk factors,and prognosis of patients with traditional Chinese medicine induced liver injury(TCM-ILI),and to analyze the proportion of TCM-ILI in drug-induced liver injury(DILI).Material and method: China National Knowledge Infrastructure,Wanfang and VIP databases were searched using the search items “zhong yao”,“cao yao”,“yao wu xing gan sun shang”,“yao wu xing gan sun hai” and “gan du xing”.Pub Med and Embase databases were searched using the search items “Traditional Chinese medicine”,“herbal medicine”,“drug-induced liver injury”,“hepatotoxicity” and “herbal induced liver injury”.Statistical analyses were performed using the Med Calc 15.2.2 and Stats Direct 2.7.8 software.The heterogeneity was evaluated using the I2 test and the Q test.Data were pooled using the random effects model.All included papers were divided into three types according to the type of data expression.Type I referred to case report with the data of every individual patient;Type II referred to case series;Type III referred to studies with the data regarding the proportion of TCM-DILI in total DILI.Results: A total of 21,027 papers were retrieved,and 624 articles were finally included.There were 178 case reports involving 321 patients,of whom 63.10% were female;the average age was 46.06±15.72;the average duration of TCMs was 78.72 ± 183.23 days;the average in-hospital length was 35.50±33.49 days.Among them,72.25%,44.49%,and 37.00% of patients presented with jaundice,anorexia,and nausea,respectively.Among them,15.26% of patients developed TCM-ILI caused by Fallopia multiflora.A total of 15 patients died.Male,low albumin,high aspartate aminotransferase,and high direct bilirubin were significantly associated with a high rate of death/liver transplantation.There were 25 case series involving 1631 patients.Meta-analyses showed that 64.49% of patients were female;64.69% of patients presented with fatigue;54.01% of patients used TCM for the treatment of Gynecology-related diseases.A total of 421 studies involving 50,988 patients reported the proportion of TCM-ILI in the overall DILI.Meta-analyses showed that the proportion of TCM-ILI was 25.71%.After excluding three non-Chinese studies,meta-analyses showed that the proportion of TCM-ILI was 25.74%.Fujian province has the lowest proportion of TCM-ILI of 18.48%;Chongqing province has the highest proportion TCM-ILI of 33.66%.The proportion of TCM-ILI was 20.43% in the elderly patients;the proportion of TCM-ILI was 31.95% in patients with liver failure.Conclusion: TCM-ILI was common in female and middle-aged patients.Jaundice and fatigue were common symptoms of TCM-ILI.Male,low albumin,high aspartate aminotransferase,and high direct bilirubin were the risk factors for worse prognosis.About one quarter of DILI in hospitalised patients was attributed to the use of TCM.