Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Johann Wolfgang Goethe-University Frankfurt/Main, Germany.
Ann Hepatol. 2010 Jul-Sep;9(3):251-65.
This review critically analyzes the clinical data of patients with suspected kava hepatotoxicity and suggests recommendations for minimizing risk. Kava is a plant (Piper methysticum) of the pepper family Piperaceae, and its rhizome is used for traditional aqueous extracts in the South Pacific Islands and for commercial ethanolic and acetonic medicinal products as anxiolytic herbs in Western countries. A regulatory ban for ethanolic and acetonic kava extracts was issued in 2002 for Germany on the basis of reports connecting liver disease with the use of kava, but the regulatory causality assessment was a matter of international discussions. Based on one positive reexposure test with the kava drug, it was indeed confirmed that kava is potentially hepatotoxic. In subsequent studies using a structured, quantitative and hepatotoxicity specific causality assessment method in 14 patients with liver disease described worldwide, causality for kava +/- comedicated drugs and dietary supplements including herbal ones was highly probable (n = 1), probable (n = 4) or possible (n = 9) regarding aqueous extracts (n = 3), ethanolic extracts (n = 5), acetonic extracts (n = 4), and mixtures containing kava (n = 2). Risk factors included overdose, prolonged treatment, and comedication with synthetic drugs and dietary supplements comprizing herbal ones in most of the 14 patients. Hepatotoxicity occurred independently of the used solvent, suggesting poor kava raw material quality as additional causative factor. In conclusion, in a few individuals kava may be hepatotoxic due to overdose, prolonged treatment, comedication, and probably triggered by an unacceptable quality of the kava raw material; standardization is now required, minimizing thereby hepatotoxic risks.
这篇综述批判性地分析了疑似卡瓦肝毒性患者的临床数据，并提出了建议，以尽量降低风险。卡瓦是胡椒科胡椒属的一种植物，其根茎用于南太平洋岛屿的传统水性提取物，以及用于西方国家的商业乙醇和丙酮药用产品作为抗焦虑草药。2002 年，基于报告将肝病与卡瓦的使用联系起来，德国对乙醇和丙酮卡瓦提取物发布了监管禁令，但监管因果关系评估是国际讨论的一个问题。基于一项对卡瓦药物的阳性再暴露测试，确实证实了卡瓦具有潜在的肝毒性。在随后的研究中，在全世界描述的 14 例肝病患者中使用结构化、定量和具有肝毒性特异性的因果关系评估方法，卡瓦 +/- 共用药和膳食补充剂（包括草药）的因果关系高度可能（n = 1）、可能（n = 4）或可能（n = 9），涉及水性提取物（n = 3）、乙醇提取物（n = 5）、丙酮提取物（n = 4）和含有卡瓦的混合物（n = 2）。在这 14 名患者中的大多数中，风险因素包括过量、长期治疗以及与合成药物和包括草药在内的膳食补充剂的共用药。肝毒性的发生与所用溶剂无关，表明卡瓦原料质量较差是另一个致病因素。总之，在少数个体中，卡瓦可能由于过量、长期治疗、共用药以及可能由于卡瓦原料质量不可接受而具有肝毒性；现在需要标准化，从而最大限度地降低肝毒性风险。
