毒理性
多达20%的使用两性霉素的患者会出现轻度和短暂的肝酶升高。临床上明显的肝毒性很少见，但已经发表了一些令人信服的病例。肝脏损伤最早可能在开始治疗后的4到14天出现，通常表现为肝细胞型或混合型的酶升高。大多数患者没有症状或黄疸。停止治疗后会迅速恢复。此外，尽管罕见但已有报告在开始使用两性霉素后的几天内出现显著的孤立性高胆红素血症，升高的主要是直接（结合）胆红素部分。这些患者会出现肉眼可见的黄疸，但没有全身症状，血清ALT或碱性磷酸酶水平几乎没有升高，也没有明显的肝脏损伤证据。最后，已有报告在接收两性霉素的患者中出现了罕见的急性胆汁淤积性肝炎并伴有黄疸，但这些患者通常病情危重，并且接触了多种可能具有肝毒性的药物，因此将病因归咎于两性霉素的依据较弱。
Mild and transient elevations in liver enzymes occur in up to 20% of patients receiving amphotericin. Clinically apparent hepatotoxicity is rare, but several convincing cases have been published. The liver injury arises as early as 4 to 14 days after starting therapy, typically with a hepatocellular or mixed pattern of enzyme elevation. Most patients have no symptoms or jaundice. Recovery occurs promptly upon stopping therapy. In addition, isolated but dramatic instances of hyperbilirubinemia arising within days of starting amphotericin have been reported with elevations largely in the direct (conjugated) bilirubin fraction. These patients become visually jaundiced but have no constitutional symptoms, minimal if any elevations in serum ALT or alkaline phosphatase levels, and no evidence of frank hepatic injury. Finally, rare instances of acute cholestatic hepatitis with jaundice have been reported in patients receiving amphotericin, but these patients have generally been critically ill and exposed to multiple potentially hepatotoxic agents, so that the attribution to amphotericin has been weak.
来源:LiverTox