胺碘酮肝毒性
一个72岁的韩国人因突然出现的腹胀被纳入了研究。他曾每日服用胺碘酮200毫克、非洛地平5毫克、双氢克尿噻25毫克、阿司匹林100毫克治疗高血压和房颤5年。在服用上述药物治疗之前，他曾经行肝脏超声和包括肝功、血脂在内的血浆生化检查，所有的结果都是正常的。没有证据表明他有乙肝、丙肝、自免肝或者代谢性疾病，如非酒精性脂肪性肝病、威尔森氏病、血色病、α1-抗胰蛋白酶缺乏病。另外，他也没有大量饮酒史。辅助检查提示大量腹腔积液、周围水肿、脾大。肝脏的化学检查是异常的：白蛋白27g/L，总胆红素2.3mg/dL, 谷草317U/L，谷丙237U/L，碱性磷酸酶137 U/L，GGT185U/L，INR1.32。经胸的超声心动图提示轻微的左心室肥大，射血分数73%，轻微的肺动脉高压。CT平扫提示弥漫性肝脏高密度和大量的腹水。经颈静脉肝活检显示肝硬化伴多核白细胞浸润， Mallory小体，气球样变性。电子显微镜显示出了肝细胞内的高密度溶酶体髓性结构。以病史和组织学为基础，胺碘酮所致肝硬化被明确诊断，胺碘酮被另外一种抗心律失常药普罗帕酮所替代。在一般状态得到改善和腹水消退后，这个患者出院了。 虽然长期应用胺碘酮导致无症状转氨酶升高的报道占到25%，在这些患者中有症状的肝功能失代偿不到1%。胺碘酮所致肝炎可进展至肝硬化，导致失代偿的肝功能衰竭，虽然比较罕见。肝损害被认为因胺碘酮所致的线粒体β氧化抑制所引起。
吉林大学第一医院肝胆胰内科 祁亚宾 摘译
本文首次发表于[Hepatology. 2012;55(1):325-326]
A 72-year-old Korean male was admitted because of sudden onset of abdominal distension. He had been treated with amiodarone 200 mg, felodipine 5 mg, hydrochlorothiazide 25 mg, and aspirin 100 mg per day for hypertension with atrial fibrillation for 5 years. Before starting medication, he had undergone ultrasonography of the liver and serum biochemical tests including liver chemistry and lipid profile, with all results being within the normal range.There was no evidence of hepatitis B and C, autoimmune hepatitis, or metabolic diseases such as nonalcoholic steatohepatitis, Wilson's disease, hemochromatosis, or α1-antitrypsin deficiency. In addition, he had no history of heavy alcohol consumption. Physical examination revealed massive ascites, peripheral edema, and splenomegaly. Liver chemistry tests were abnormal: serum albumin = 2.7 g/dL, total bilirubin = 2.3 mg/dL, aspartate aminotransferase = 317 U/L, alanine aminotransferase = 237 U/L, alkaline phosphatase = 137 U/L, gamma-glutamyl transpeptidase = 185 U/L, and international normalized ratio = 1.32.A transthoracic echocardiogram showed mild concentric left ventricular hypertrophy, ejection fraction of 73%, and mild pulmonary hypertension. A precontrast computed tomography scan showed a diffusely hyperdense liver and a large amount of ascites (Panel A). Transjugular liver biopsy demonstrated cirrhosis with polymorphonuclear infiltrate, Mallory bodies (arrows), and ballooning degeneration (arrowheads) (Panel B). Electron microscopy showed lysosomal myeloid bodies with dense deposits (asterisks) within hepatocytes (Panel C).On the basis of clinical history and histologic findings, amiodarone-induced liver cirrhosis was diagnosed, and the drug was replaced with another antiarrhythmic agent (propafenone). He was discharged with improved general condition with marked reduction of ascites.Although asymptomatic elevations of aminotransferases have been reported in up to 25% of the patients treated with long-term amiodarone therapy, symptomatic liver dysfunction has been reported to occur in fewer than 1% of these patients. However, amiodarone-induced hepatitis can progress to cirrhosis, resulting in decompensated hepatic failure, although this rarely happens.liver damage is considered to be caused by amiodarone-induced inhibition of mitochondrial β-oxidation.
