AIM To analyze liver tests before and following treatment with herbal Traditional Chinese Medicine(TCM) in order to evaluate the frequency of newly detected liver injury.METHODS Patients with normal values of alanine ...AIM To analyze liver tests before and following treatment with herbal Traditional Chinese Medicine(TCM) in order to evaluate the frequency of newly detected liver injury.METHODS Patients with normal values of alanine aminotransferase(ALT) as a diagnostic marker for ruling out pre-existing liver disease were enrolled in a prospective study of a safety program carried out at the First German Hospital of TCM from 1994 to 2015. All patients received herbal products, and their ALT values were reassessed 1-3 d prior to discharge. To verify or exclude causality for suspected TCM herbs, the Roussel Uclaf Causality Assessment Method(RUCAM) was used.RESULTS This report presents for the first time liver injury data derived from a prospective, hospital-based and largescale study of 21470 patients who had no liver disease prior to treatment with herbal TCM. Among these, ALT ranged from 1 × to < 5 × upper limit normal(ULN) in 844 patients(3.93%) and suggested mild or moderate liver adaptive abnormalities. However, 26 patients(0.12%) experienced higher ALT values of ≥ 5 × ULN(300.0 ± 172.9 U/L, mean ± SD). Causality for TCM herbs was RUCAM-based probable in 8/26 patients, possible in 16/26, and excluded in 2/26 cases. Bupleuri radix and Scutellariae radix were the two TCM herbs most commonly implicated. CONCLUSION In 26(0.12%) of 21470 patients treated with herbal TCM, liver injury with ALT values of ≥ 5 × ULN was found, which normalized shortly following treatment cessation, also substantiating causality.展开更多
Herb-induced liver injuries (HILI) by traditional herbal medi-cines are particular challenges in Asian countries, with issues over the best approach to establish causality. The aim of the current analysis was to provi...Herb-induced liver injuries (HILI) by traditional herbal medi-cines are particular challenges in Asian countries, with issues over the best approach to establish causality. The aim of the current analysis was to provide an overview on how causality was assessed in HILI cases from Asian countries and whether the Roussel Uclaf Causality Assessment Method (RUCAM) was the preferred diagnostic algorithm, as shown before in world-wide evaluated cases of drug-induced liver injury (DILI). Using the PubMed database, publications in English language were preferred to allow for reevaluation by peers. Overall 11,160 HILI cases have assessed causality using RUCAM and were published by first authors working in Asian countries. With 21 evaluable reports, most publications came from China's Mainland, with Hong Kong and Taiwan, followed by Korea (n=15), Singapore (n=2), and Japan (n=1), while other Asian countries were not contributory. Most publications provided case and RUCAM data of good quality. For better presentation of future cases, how-ever, the following recommendations are given:(1) preference of prospective study design with use of the updated RUCAM version;(2) clear separation of HILI cohorts from those of other herbal products or DILI;(3) case series for epidemiology stud-ies should contain many essential data, possibly also as supple-mentary material;(4) otherwise, preference of single case reports providing individual case data and RUCAM-based cau-sality gradings, and applying liver test threshold values;and (5) publication in English language journals. In conclusion, China and Korea are top in presenting RUCAM-based HILI cases, other Asian countries are encouraged to follow.展开更多
With growing antipathy toward conventional prescription drugs due to the fear of adverse events,the general and patient populations have been increasingly using complementary and alternative medications(CAMs)for manag...With growing antipathy toward conventional prescription drugs due to the fear of adverse events,the general and patient populations have been increasingly using complementary and alternative medications(CAMs)for managing acute and chronic diseases.The general misconception is that natural herbal-based preparations are devoid of toxicity,and hence short-and long-term use remain justified among people as well as the CAM practitioners who prescribe these medicines.In this regard,Ayurvedic herbal medications have become one of the most utilized in the East,specifically the Indian sub-continent,with increasing use in the West.Recent well-performed observational studies have confirmed the hepatotoxic potential of Ayurvedic drugs.Toxicity stems from direct effects or from indirect effects through herbal metabolites,unknown herb-herb and herbdrug interactions,adulteration of Ayurvedic drugs with other prescription medicines,and contamination due to poor manufacturing practices.In this exhaustive review,we present details on their hepatotoxic potential,discuss the mechanisms,clinical presentation,liver histology and patient outcomes of certain commonly used Ayurvedic herbs which will serve as a knowledge bank for physicians caring for liver disease patients,to support early identification and treatment of those who present with CAM-induced liver injury.展开更多
Traditional Chinese Medicine (TCM) is popular around the world and encompasses many different practices with parti-cular emphasis on herbal TCM. Using the PubMed database, a literature search was undertaken to assess ...Traditional Chinese Medicine (TCM) is popular around the world and encompasses many different practices with parti-cular emphasis on herbal TCM. Using the PubMed database, a literature search was undertaken to assess the extent herbal TCM products exert rare hepatotoxicity. Analysis of reported cases revealed numerous specified herbal TCM products with potential hepatotoxicity. Among these were An Shu Ling, Bai Fang, Bai Xian Pi, Ban Tu Wan, Bo He, Bo Ye Qing Niu Dan, Bofu Tsu Sho San, Boh Gol Zhee, Cang Er Zi, Chai Hu, Chaso, Chi R Yun, Chuan Lian Zi, Ci Wu Jia, Da Chai Hu Tang, Da Huang, Du Huo, Gan Cao, Ge Gen, Ho Shou Wu, Hu Bohe You, Hu Zhang, Huang Qin, Huang Yao Zi, Hwang Geun Cho, Ji Gu Cao, Ji Ji, Ji Xue Cao, Jiguja, Jin Bu Huan, Jue Ming Zi, Kamishoyosan, Kudzu, Lei Gong Teng, Long Dan Xie Gan Tang, Lu Cha, Ma Huang, Mao Guo Tian Jie Cai, Onshido, Polygonum multiflorum, Qian Li Guang, Ren Shen, Sairei To, Shan Chi, Shen Min, Shi Can, Shi Liu Pi, Shou Wu Pian, Tian Hua Fen, White flood, Wu Bei Zi, Xi Shu, Xiao Chai Hu Tang, Yin Chen Hao, Zexie, Zhen Chu Cao, and various unclassified Chinese herbal mixtures. Causality was firmly established for a number of herbal TCM products by a positive reexposure test result, the liver specific scale of CIOMS (Council for International Organizations of Medical Sciences), or both. Otherwise, the quality of case data was mixed, especially regarding analysis of the herb ingredients because of adulteration with synthetic drugs, contamination with heavy metals, and misidentification. In addition, non-herbal TCM elements derived from Agaricus blazei, Agkistrodon, Antelope, Bombyx, Carp, Fish gallbladder, Phellinus, Scolopendra, Scorpio, and Zaocys are also known or potential hepatotoxins. For some patients, the clinical course was severe, with risks for acute liver failure, liver transplantation requirement, and lethality. In conclusion, the use of few herbal TCM products may rarely be associated with hepatotoxicity in some susceptible individuals, necessitating a stringent pretreatment evaluation of the risk/benefit ratio, based on results of multicenter, randomized, double-blind, placebo-controlled clinical trials.展开更多
文摘AIM To analyze liver tests before and following treatment with herbal Traditional Chinese Medicine(TCM) in order to evaluate the frequency of newly detected liver injury.METHODS Patients with normal values of alanine aminotransferase(ALT) as a diagnostic marker for ruling out pre-existing liver disease were enrolled in a prospective study of a safety program carried out at the First German Hospital of TCM from 1994 to 2015. All patients received herbal products, and their ALT values were reassessed 1-3 d prior to discharge. To verify or exclude causality for suspected TCM herbs, the Roussel Uclaf Causality Assessment Method(RUCAM) was used.RESULTS This report presents for the first time liver injury data derived from a prospective, hospital-based and largescale study of 21470 patients who had no liver disease prior to treatment with herbal TCM. Among these, ALT ranged from 1 × to < 5 × upper limit normal(ULN) in 844 patients(3.93%) and suggested mild or moderate liver adaptive abnormalities. However, 26 patients(0.12%) experienced higher ALT values of ≥ 5 × ULN(300.0 ± 172.9 U/L, mean ± SD). Causality for TCM herbs was RUCAM-based probable in 8/26 patients, possible in 16/26, and excluded in 2/26 cases. Bupleuri radix and Scutellariae radix were the two TCM herbs most commonly implicated. CONCLUSION In 26(0.12%) of 21470 patients treated with herbal TCM, liver injury with ALT values of ≥ 5 × ULN was found, which normalized shortly following treatment cessation, also substantiating causality.
文摘Herb-induced liver injuries (HILI) by traditional herbal medi-cines are particular challenges in Asian countries, with issues over the best approach to establish causality. The aim of the current analysis was to provide an overview on how causality was assessed in HILI cases from Asian countries and whether the Roussel Uclaf Causality Assessment Method (RUCAM) was the preferred diagnostic algorithm, as shown before in world-wide evaluated cases of drug-induced liver injury (DILI). Using the PubMed database, publications in English language were preferred to allow for reevaluation by peers. Overall 11,160 HILI cases have assessed causality using RUCAM and were published by first authors working in Asian countries. With 21 evaluable reports, most publications came from China's Mainland, with Hong Kong and Taiwan, followed by Korea (n=15), Singapore (n=2), and Japan (n=1), while other Asian countries were not contributory. Most publications provided case and RUCAM data of good quality. For better presentation of future cases, how-ever, the following recommendations are given:(1) preference of prospective study design with use of the updated RUCAM version;(2) clear separation of HILI cohorts from those of other herbal products or DILI;(3) case series for epidemiology stud-ies should contain many essential data, possibly also as supple-mentary material;(4) otherwise, preference of single case reports providing individual case data and RUCAM-based cau-sality gradings, and applying liver test threshold values;and (5) publication in English language journals. In conclusion, China and Korea are top in presenting RUCAM-based HILI cases, other Asian countries are encouraged to follow.
文摘With growing antipathy toward conventional prescription drugs due to the fear of adverse events,the general and patient populations have been increasingly using complementary and alternative medications(CAMs)for managing acute and chronic diseases.The general misconception is that natural herbal-based preparations are devoid of toxicity,and hence short-and long-term use remain justified among people as well as the CAM practitioners who prescribe these medicines.In this regard,Ayurvedic herbal medications have become one of the most utilized in the East,specifically the Indian sub-continent,with increasing use in the West.Recent well-performed observational studies have confirmed the hepatotoxic potential of Ayurvedic drugs.Toxicity stems from direct effects or from indirect effects through herbal metabolites,unknown herb-herb and herbdrug interactions,adulteration of Ayurvedic drugs with other prescription medicines,and contamination due to poor manufacturing practices.In this exhaustive review,we present details on their hepatotoxic potential,discuss the mechanisms,clinical presentation,liver histology and patient outcomes of certain commonly used Ayurvedic herbs which will serve as a knowledge bank for physicians caring for liver disease patients,to support early identification and treatment of those who present with CAM-induced liver injury.
文摘Traditional Chinese Medicine (TCM) is popular around the world and encompasses many different practices with parti-cular emphasis on herbal TCM. Using the PubMed database, a literature search was undertaken to assess the extent herbal TCM products exert rare hepatotoxicity. Analysis of reported cases revealed numerous specified herbal TCM products with potential hepatotoxicity. Among these were An Shu Ling, Bai Fang, Bai Xian Pi, Ban Tu Wan, Bo He, Bo Ye Qing Niu Dan, Bofu Tsu Sho San, Boh Gol Zhee, Cang Er Zi, Chai Hu, Chaso, Chi R Yun, Chuan Lian Zi, Ci Wu Jia, Da Chai Hu Tang, Da Huang, Du Huo, Gan Cao, Ge Gen, Ho Shou Wu, Hu Bohe You, Hu Zhang, Huang Qin, Huang Yao Zi, Hwang Geun Cho, Ji Gu Cao, Ji Ji, Ji Xue Cao, Jiguja, Jin Bu Huan, Jue Ming Zi, Kamishoyosan, Kudzu, Lei Gong Teng, Long Dan Xie Gan Tang, Lu Cha, Ma Huang, Mao Guo Tian Jie Cai, Onshido, Polygonum multiflorum, Qian Li Guang, Ren Shen, Sairei To, Shan Chi, Shen Min, Shi Can, Shi Liu Pi, Shou Wu Pian, Tian Hua Fen, White flood, Wu Bei Zi, Xi Shu, Xiao Chai Hu Tang, Yin Chen Hao, Zexie, Zhen Chu Cao, and various unclassified Chinese herbal mixtures. Causality was firmly established for a number of herbal TCM products by a positive reexposure test result, the liver specific scale of CIOMS (Council for International Organizations of Medical Sciences), or both. Otherwise, the quality of case data was mixed, especially regarding analysis of the herb ingredients because of adulteration with synthetic drugs, contamination with heavy metals, and misidentification. In addition, non-herbal TCM elements derived from Agaricus blazei, Agkistrodon, Antelope, Bombyx, Carp, Fish gallbladder, Phellinus, Scolopendra, Scorpio, and Zaocys are also known or potential hepatotoxins. For some patients, the clinical course was severe, with risks for acute liver failure, liver transplantation requirement, and lethality. In conclusion, the use of few herbal TCM products may rarely be associated with hepatotoxicity in some susceptible individuals, necessitating a stringent pretreatment evaluation of the risk/benefit ratio, based on results of multicenter, randomized, double-blind, placebo-controlled clinical trials.
