Hepatic Phospholipidosis Is Associated with Altered Hepatobiliary Function as Assessed by Gadoxetate Dynamic Contrast-enhanced Magnetic Resonance Imaging
Hepatic Phospholipidosis Is Associated with Altered Hepatobiliary Function as Assessed by Gadoxetate Dynamic Contrast-enhanced Magnetic Resonance Imaging
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DOI：
10.1177/0192623315608509
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发表时间：
2016-01-01
影响因子：
1.5
通讯作者：
Jucker, Beat M.
中科院分区：
文献类型：
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作者：
Lenhard, Stephen C.;Lev, Mally;Jucker, Beat M.
为确定胺碘酮是否诱导足以检测肝胆转运蛋白功能变化的肝磷脂质沉积症（PLD）（通过钆塞酸盐动态对比增强磁共振成像（DCE-MRI）评估），大鼠连续7天经口给予溶剂（1%甲基纤维素）或胺碘酮（300 mg/kg/天）。在基线、第7天和胺碘酮洗脱2周后进行甘氨酯DCE-MRI。在第7天，钆塞酸盐洗脱率与溶媒组相比显著降低。血液化学分析显示，溶剂组或胺碘酮组之间的肝酶（丙氨酸氨基转移酶[ALT]/天冬氨酸氨基转移酶[AST]/碱性磷酸酶[ALP]）、胆红素或胆汁酸无显著变化。在第7天，通过透射电子显微镜检查，在接受胺碘酮治疗的所有大鼠中证实了肝脏PLD。2周洗脱后，大鼠中无肝脏PLD的超微结构证据，钆塞酸盐洗脱率恢复至基线水平。这是第一项显示钆塞酸盐DCE-MRI应用于检测与PLD相关的肝胆功能变化的研究，并为疑似PLD患者提供了具有临床实用性的潜在新技术。这些结果还表明，在没有毒性生物标志物的情况下，PLD本身对肝胆功能具有功能性后果，因为PLD与功能之间的因果关系尚未完全确立。
To determine if amiodarone induces hepatic phospholipidosis (PLD) sufficient to detect changes in hepatobiliary transporter function as assessed by gadoxetate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), rats were orally dosed with vehicle (1% methyl cellulose) or amiodarone (300 mg/kg/day) for 7 consecutive days. Gadoxetate DCE-MRI occurred at baseline, day 7, and following a 2-week washout of amiodarone. At day 7, the gadoxetate washout rate was significantly decreased compared to the vehicle group. Blood chemistry analysis revealed no significant changes in liver enzymes (alanine aminotransferase [ALT]/aspartate aminotransferase [AST]/alkaline phosphatase [ALP]), bilirubin, or bile acids between vehicle or amiodarone groups. Hepatic PLD was confirmed in all rats treated with amiodarone at day 7 by transmission electron microscopy. Following the 2-week washout, there was no ultrastructural evidence of hepatic PLD in rats and the gadoxetate washout rate returned to baseline levels. This is the first study to show the application of gadoxetate DCE-MRI to detect hepatobiliary functional changes associated with PLD and offer a potential new technique with clinical utility in patients suspected of having PLD. These results also suggest PLD itself has functional consequences on hepatobiliary function in the absence of biomarkers of toxicity, given the cause/effect relationship between PLD and function has not been fully established.