Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Goethe University Frankfurt/Main, Germany.
Regul Toxicol Pharmacol. 2011 Dec;61(3):282-91. doi: 10.1016/j.yrtph.2011.08.008. Epub 2011 Aug 27.
Toxic liver injury due to the herb Greater Celandine (GC) (Chelidonium majus L.) has been assumed in patients originating from various European countries and created concern. Based on regulatory and liver unspecific ad hoc causality assessments in 22 spontaneous cases of Germany, causality levels for GC were considered probable in 16 and possible in 6 cases. We now analyzed the data of these 22 cases regarding their causality levels employing the liver specific, standardized, structured and quantitative assessment method of the updated scale of CIOMS (Council for International Organizations of Medical Sciences). Causality for GC was found highly probable (n=2), probable (n=6), possible (n=10), unlikely (n=1), and excluded (n=3). Thus, causality could be upgraded in 2 cases to a highly probable causality level, but had to be down graded to excluded, unlikely, or possible causality levels in 3, 1, or 9 cases, respectively. GC hepatotoxicity shows a hepatocellular pattern of liver injury with female gender predominance. On average, age of the patients was 56.4 years, treatment 36.4 days, and latency period until first symptoms and jaundice 29.8 and 35.6 days, respectively. This analysis therefore provides further evidence for the existence of GC hepatotoxicity as a distinct form of herb induced liver injury, but due to poor data quality the causal association between GC use and liver injury is less strong than hitherto assumed. We propose replacement of the regulatory organ unspecific by a liver specific causality assessment method in cases of herb induced liver injury as well as stricter pharmacovigilance strategies towards improvements of data quality. Toxicological studies are now warranted to elucidate the mechanism(s) of human GC hepatotoxicity that represents a European issue.
由于草药白屈菜（GC）（Chelidonium majus L.）引起的肝毒性损伤，已在来自欧洲各国的患者中被认为存在，并引起了关注。基于对德国 22 例自发病例的监管和非肝脏特异性专门因果关系评估，GC 的因果关系水平被认为在 16 例中为可能，在 6 例中为可能。我们现在使用更新的 CIOMS（国际医学组织理事会）标准、标准化、结构化和定量评估方法，分析了这些 22 例病例的数据，以评估其因果关系水平。GC 的因果关系被认为高度可能（n=2）、可能（n=6）、可能（n=10）、不太可能（n=1）和排除（n=3）。因此，因果关系可以在 2 例中升级为高度可能的因果关系水平，但在 3 例、1 例或 9 例中分别降级为排除、不太可能或可能的因果关系水平。GC 肝毒性表现为肝细胞性肝损伤，女性性别为主。患者的平均年龄为 56.4 岁，治疗时间为 36.4 天，首次出现症状和黄疸的潜伏期分别为 29.8 天和 35.6 天。因此，本分析进一步证明了 GC 肝毒性作为一种独特的草药诱导性肝损伤形式的存在，但由于数据质量较差，GC 使用与肝损伤之间的因果关系不如以前假设的那么强。我们建议在草药诱导性肝损伤的情况下，用肝脏特异性因果关系评估方法替代监管机构非特异性方法，并采取更严格的药物警戒策略，以提高数据质量。目前需要进行毒理学研究，以阐明人类 GC 肝毒性的机制，这是一个欧洲问题。
