草药和补充医学经常与传统医学相结合。我们的目的是报告一例由于长期使用绿茶和蛋白质奶昔引起的严重草药诱导的肝损伤(HILI)。我们提供了临床和实验室证据,表明线粒体毒性和免疫反应导致对产品的超敏反应。我们最近治疗了一名39岁的男性,该男性患有肝毒性,该肝毒性是由含绿茶的粉末和2个月前开始的支链氨基酸补充剂的组合引起的。通过停止这些产品的消耗解决了肝毒性,并且没有检测到其他原因。我们决定进行淋巴细胞毒性测定(LTA),以确定是否有实验室支持该诊断。LTA(%毒性)代表线粒体对毒性损伤的响应。确定促炎和抗炎细胞因子和趋化因子在患者反应中的作用,我们测量了生长细胞培养基中细胞因子和趋化因子的水平,暴露于每种产品或产品的组合。增加的细胞因子和趋化因子表示为基质金属蛋白酶(MMP)(pg/mL×1.5ULN)和白介素(IL)-1β(pg/mL×1.8ULN)的正常上限(ULN)的x倍升高。发现干扰素(IFN)-β升高较高,IFN-γ,IL-8,IL13,IL-15(pg/mL×2ULN),在激活时调节,正常T细胞表达和可能分泌(RANTES)(pg/mL×2ULN),核因子(NFκB)(pg/mL×3ULN)。增加最高的是血管内皮因子(VEGF)(pg/mL×10ULN),肿瘤坏死因子(TNF)-α,肿瘤坏死因子相关凋亡诱导配体(TRAIL)(pg/mL×13ULN)。细胞标志物的检查显示程序性细胞死亡(凋亡)和由于坏死引起的细胞死亡之间的差异。在我们的案例中,细胞角蛋白CCK18(M-30)U/L在正常范围内,表明细胞凋亡是正常的,ccK8(M65)U/L升高至1.5×ULN。这一结果表明,在用产品治疗患者的淋巴细胞时,毒性的机制是坏死。在易感个体中,蛋白质和凉茶的组合产生线粒体毒性和强烈的T淋巴细胞-1反应,通向HILI。临床医生需要对药物不良反应进行国际报告,实验室,和药品制造商向药品监管部门。这需要国际公认的反应标准定义,以及评估标准。
Herbal and complementary medicine are frequently integrated with conventional medicine. We aim to report a
case of severe herbal-induced liver injury (HILI) due to chronic use of green tea and protein shake. We present both clinical and laboratory evidence implicating mitochondrial toxicity and an immune response leading to a hypersensitivity reaction to the products. We have recently treated a 39-year-old man with hepatotoxicity resulting from a combination of a green tea-containing powder and a branched-chain amino acid supplement that was commenced 2 months previously. The hepatotoxicity resolved by stopping the consumption of these products and no other cause was detected. We decided to perform a lymphocyte toxicity assay (LTA) to determine if there was laboratory support for this diagnosis. LTA (% toxicity) represents the response of the mitochondria to toxic injury. To determine the role of the proinflammatory and anti-inflammatory cytokines and chemokines in the patient\'s reaction, we measured the level of cytokines and chemokine in the media of growing cells, exposed to each product or to a combination of products. The increased cytokines and chemokines are presented as the x-fold elevations from the upper limit of normal (ULN) for matrix metalloproteinase (MMP) (pg/mL × 1.5 ULN) and interleukin (IL)-1β (pg/mL × 1.8 ULN). Higher elevations were found for interferon (IFN)-β, IFN-γ, IL-8, IL 13, IL-15 (pg/mL × 2 ULN), regulated upon activation, normal T cell expressed and presumably secreted (RANTES) (pg/mL × 2 ULN), and nuclear factor (NFκB) (pg/mL × 3 ULN). The highest increases were for vascular endothelial factor (VEGF) (pg/mL × 10 ULN), tumor necrosis factor (TNF)-α, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (pg/mL × 13 ULN). An examination of cellular markers showed the difference between programmed cell death (apoptosis) and cell death due to necrosis. In our
case, cytokeratin-ccK18 (M-30) U/L was within the normal limits, suggesting that apoptosis was normal, while ccK8(M65) U/L was elevated at 1.5 × ULN. This result implies that upon the treatment of the patient\'s lymphocytes with the products, the mechanism of toxicity is necrosis. In susceptible individuals, the combination of protein and herbal tea produces mitochondrial toxicity and a strong T-lymphocyte-1 response, leading to HILI. There is a need of international reporting of adverse drug reactions by clinicians, laboratories, and pharmaceutical manufacturers to drug regulatory authorities. This requires internationally accepted standard definitions of reactions, as well as criteria for assessment.