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阿托伐他汀为3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶选择性抑制剂,是一种具有良好降血脂效果的降脂药。阿托伐他汀可引起剂量依赖性血清氨基转移酶升高,常伴有肝脏肿大、黄疸、直接胆红素升高、凝血酶原时间延长等。阿托伐他汀致肝损伤的类型有:细胞毒型、胆汁淤积型和混合型。阿托伐他汀致细胞毒型肝损伤的机制可能是通过竞争性抑制HMG-CoA还原酶,引起肝细胞染色体DNA断裂和细胞形态学变化,导致肝细胞凋亡所致。阿托伐他汀致胆汁淤积型肝损伤的机制可能是使肝细胞窦状隙膜或胆管侧膜上转运体表达减少或功能障碍,或通过抑制胆盐和胆汁酸排泄相关转运蛋白的活性所致。防治阿托伐他汀致肝损伤措施包括:应用阿托伐他汀前,应检测患者肝脏功能,了解病史、其他用药及饮酒习惯等;建议从小剂量开始应用。因服用阿托伐他汀致轻中度转氨酶升高者可减少用药剂量,服用保肝利胆等药物;严重肝损伤者应立即停药并对症治疗。
Atorvastatin, a selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, is a lipid-lowering drug with good hypolipidemic effect. Atorvastatin can cause dose-dependent serum aminotransferase increased, often accompanied by liver enlargement, jaundice, direct bilirubin, prothrombin time and so on. Atorvastatin-induced liver injury types are: cytotoxic, cholestatic and mixed type. Atorvastatin induced cytotoxic liver damage may be through the mechanism of competitive inhibition of HMG-CoA reductase, causing chromosome DNA damage in liver cells and cell morphological changes, leading to apoptosis caused by liver cells. Mechanism of atorvastatin-induced cholestatic liver injury may be due to diminished or dysfunctional expression of hepatic sinusoidal or bile duct side membrane transporters in hepatocytes or by inhibiting the activity of bile salts and bile acid excretion-associated transporters . Prevention and treatment of atorvastatin caused by liver damage include: application of atorvastatin, liver function should be tested before, to understand the history, other medication and drinking habits, etc .; recommended starting from a small dose. Due to taking atorvastatin caused by mild to moderate transaminase increased dosage can reduce the dose of taking liver and gallbladder and other drugs; severe liver injury should be immediately discontinued and symptomatic treatment.