Background Approximately 30 million people worldwide consume new psychoactive substances (NPS), creating a serious public health issue due to their toxicity and potency. Drug-induced liver injury is the leading cause of liver disease, responsible for 4% of global deaths each year. Content A systematic literature search revealed 64 case reports, in vitro and in vivo studies on NPS hepatotoxicity. Maximum elevated concentrations of aspartate aminotransferase (136 to 15 632 U/L), alanine transaminase (121.5 to 9162 U/L), total bilirubin (0.7 to 702 mg/dL; 0.04 to 39.03 mmol/L), direct (0.2–15.1 mg/dL; 0.01–0.84 mmol/L) and indirect (5.3 mg/dL; 0.29 mmol/L) bilirubin, alkaline phosphatase (79–260 U/L), and gamma-glutamyltransferase (260 U/L) were observed as biochemical markers of liver damage, with acute and fulminant liver failure the major toxic effects described in the NPS case reports. In vitro laboratory studies and subsequent in vivo NPS exposure studies on rats and mice provide data on potential mechanisms of toxicity. Oxidative stress, plasma membrane stability, and cellular energy changes led to apoptosis and cell death. Experimental studies of human liver microsome incubation with synthetic NPS, with and without specific cytochrome P450 inhibitors, highlighted specific enzyme inhibitions and potential drug–drug interactions leading to hepatotoxicity. Summary Mild to severe hepatotoxic effects following synthetic NPS exposure were described in case reports. In diagnosing the etiology of liver damage, synthetic NPS exposure should be considered as part of the differential diagnosis. Identification of NPS toxicity is important for educating patients on the dangers of NPS consumption and to suggest promising treatments for observed hepatotoxicity.

中文翻译：

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接触合成精神活性物质：人类肝毒性标志物增加的潜在原因

背景 全世界大约有 3000 万人消费新型精神活性物质 (NPS)，由于其毒性和效力造成了严重的公共健康问题。药物性肝损伤是肝病的主要原因，每年导致全球死亡人数的 4%。内容 系统文献检索发现 64 例 NPS 肝毒性的体外和体内研究病例报告。天冬氨酸转氨酶（136 至 15 632 U/L）、丙氨酸转氨酶（121.5 至 9162 U/L）、总胆红素（0.7 至 702 mg/dL；0.04 至 39.03 mmol/L）、直接（0.2–15.1）的最大浓度升高mg/dL；0.01–0.84 mmol/L）和间接（5.3 mg/dL；0.29 mmol/L）胆红素、碱性磷酸酶（79–260 U/L）和 γ-谷氨酰转移酶（260 U/L）被观察为肝损伤的生化标志物，其中急性和暴发性肝衰竭是 NPS 病例报告中描述的主要毒性作用。体外实验室研究和随后对大鼠和小鼠的体内 NPS 暴露研究提供了潜在毒性机制的数据。氧化应激、质膜稳定性和细胞能量变化导致细胞凋亡和细胞死亡。将人肝微粒体与合成 NPS 一起孵育（在有或没有特定细胞色素 P450 抑制剂的情况下）的实验研究强调了特定的酶抑制作用和导致肝毒性的潜在药物间相互作用。摘要 病例报告中描述了合成 NPS 暴露后的轻度至重度肝毒性影响。在诊断肝损伤的病因时，合成 NPS 暴露应被视为鉴别诊断的一部分。NPS 毒性的识别对于教育患者了解 NPS 消耗的危险以及针对观察到的肝毒性提出有希望的治疗方法非常重要。