Literature Review of Traditional Chinese Medicine Herbs–Induced Liver Injury From an Oncological Perspective With RUCAM

Abstract

Traditional Chinese medicine (TCM) herbs are commonly regarded to be safe with minimal toxicities in Chinese communities. Cancer patients who are receiving Western oncology therapy often concurrently take TCM herbs for anticancer and symptom relief purposes. We performed a literature review for current evidence on TCM herb–induced liver injury from an oncological perspective. A literature search on PubMed was performed to identify publications regarding TCM herbs and concoctions with hepatoprotective or hepatotoxic properties. Lists of commonly used herbs and their causality levels were compiled. In view of the wide range of evidence available, cases assessed by the well-established RUCAM (Roussel Uclaf Causality Assessment Method) algorithm were categorized as the highest level of evidence. More than one case of TCM herb–induced liver injury was confirmed by RUCAM in the following herbs and concoctions: Lu Cha ( Camellia sinensis), Bai Xian Pi ( Dictamnus dasycarpus), Tu San Qi ( Gynura segetum), Jin Bu Huan ( Lycopodium serratum), He Shou Wu ( Polygoni multiflora), Ge Gen ( Pueraria lobata), Dan Lu Tong Du tablet, Shou Wu Pian, Xiao Chai Hu Tang, Xiao Yin pill, and Yang Xue Sheng Fa capsule. Finally, TCM with anticancer or symptom relief uses were discussed in detail with regard to their hepatotoxic or hepatoprotective properties.

Worldwide Use of RUCAM for Causality Assessment in 81,856 Idiosyncratic DILI and 14,029 HILI Cases Published 1993–Mid 2020: A Comprehensive Analysis

“…Authors from many countries around the world reported on cases of HILI in connection with the consumption of various herbs, all published since 1993 ( Table 4 ) [ 29 , 37 , 38 , 42 , 48 , 100 , 101 , 102 , 103 , 113 , 115 , 116 , 117 , 118 , 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 , 210 , 211 , 212 , 213 , 214 , 215 , 216 ,…”

“…In particular, contributing countries were in alphabetical order Australia [ 29 ], Brazil [ 183 ], China [ 48 , 196 , 197 , 198 , 199 , 200 , 201 ], Germany [ 213 , 214 , 215 ], India [ 217 ], Italy [ 222 ], Korea [ 103 ], Spain [ 115 , 117 , 240 , 241 , 242 ], Switzerland [ 244 ], and the US [ 245 , 246 , 247 , 248 , 249 , 250 , 251 , 252 , 253 , 254 ]. Most of the 11,619 HILI cases published in 2019 were from China [ 48 , 196 ] and Korea [ 103 ], with 6971 cases published by Shen et al [ 48 ], 2019 cases reported by Byeon et al [ 103 ], and 1552 cases provided by Chow et al [ 196 ]. However, until mid 2020 only 57 HILI cases were published ( Table 4 ) [ 202 , 203 , 253 , 254 ], suggesting for the whole year 2020 at best 100 cases ( Figure 3 ).…”

Case series and review of Ayurvedic medication induced liver injury

“…Although Tinospora cordifolia (contained in Gilroy Kvath taken by patient 1 and in Manjishthadi Kwatham taken by patient 2) was not reported among TCM, a closely related plant species, Tinospora crispa , is contained in Bo Ye Qing Niu Dan which has been associated with liver injury [ 31 , 32 ]. Azadirachta indica contained in Manjishthadi Kwatham is found in Ku Lian Zi as well as Cinnamomum tamala (Indian bay leaf) that is contained in Sairei To, which has been reported to cause DILI in TCM supplements [ 31 – 33 ].…”

Herb-induced Liver Injury in Asia and Current Role of RUCAM for Causality Assessment in 11,160 Published Cases

“…In addition and as shown in their report assessing causality by Gao et al , 25 RUCAM was used for the first time in the hepatic sinusoidal obstruction syndrome caused by PAs in 23 patients, supporting the blood pyrrole-protein adducts as diagnostic biomarkers. 25 The reports of Hao et al , 24 Chow et al 32 and Tan et al 37 are worth mentioning because these authors clarify, already in their title, that cases had been assessed for causality using RUCAM. Tan et al 37 also carefully assessed the comedicated drug using a separate RUCAM sheet, as recommended earlier.…”