Takeyama Yasuaki, Tsuchiya Naoaki, Kunimoto Hideo, Fukunaga Atsushi, Sakurai Kunitoshi, Hirano Genryu, Yokoyama Keiji, Morihara Daisuke, Anan Akira, Irie Makoto, Shakado Satoshi, Sohda Tetsuro, Sakisaka Shotaro
Department of Gastroenterology and Medicine, Fukuoka University Faculty of Medicine, Fukuoka, Japan.
Hepatol Res. 2015 Oct;45(10):E108-14. doi: 10.1111/hepr.12470. Epub 2015 Mar 2.
In primary biliary cirrhosis (PBC), damaged hepatocytes resulting from chronic cholestasis follow a compensatory mechanism that alters hepatobiliary transporter expression to reduce the accumulation of potentially toxic compounds such as bile acid. Organic anion transporter peptide 1B3 (OATP1B3), which transports agents such as gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), has reduced expression in the late stages of PBC. Therefore, we investigated the use of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) as a useful detection method for the advanced staging of PBC.
Stage I-III PBC (non-liver cirrhosis [LC]-PBC, n = 12), stage IV (LC-PBC, n = 6), and non-PBC patients (control group, n = 4) were included in this study. We obtained liver tissue samples by percutaneous liver biopsy. Hepatic OATP1B3 expression was determined immunohistochemically, and OATP1B3 mRNA levels were assessed using real-time reverse transcription polymerase chain reaction. The relative enhancement (RE) in the hepatobiliary phase was calculated using the signal intensity of Gd-EOB-DTPA-enhanced MRI.
Immunohistochemistry revealed markedly reduced expression of OATP1B3 in hepatocytes around the central vein in LC-PBC patients. Hepatic OATP1B3 mRNA expression in LC-PBC patients was significantly lower than that in non-LC-PBC patients (P < 0.05). The RE on MRI was significantly decreased in the LC-PBC group (0.33 ± 0.14) compared with the non-LC-PBC (0.91 ± 0.15, P < 0.01) and control (0.92 ± 0.20, P < 0.01) groups.
Gd-EOB-DTPA-enhanced MRI may provide a useful detection method for liver disease in patients with LC-PBC.
在原发性胆汁性肝硬化(PBC)中,慢性胆汁淤积导致的肝细胞损伤遵循一种代偿机制,该机制会改变肝胆转运体的表达,以减少潜在有毒化合物如胆汁酸的蓄积。有机阴离子转运多肽1B3(OATP1B3)可转运钆-乙氧基苄基-二乙三胺五乙酸(Gd-EOB-DTPA)等物质,其在PBC晚期表达降低。因此,我们研究了Gd-EOB-DTPA增强磁共振成像(MRI)作为PBC晚期分期有用检测方法的应用。
本研究纳入了I-III期PBC(非肝硬化[LC]-PBC,n = 12)、IV期(LC-PBC,n = 6)患者以及非PBC患者(对照组,n = 4)。我们通过经皮肝穿刺活检获取肝组织样本。采用免疫组织化学法测定肝脏OATP1B3表达,并使用实时逆转录聚合酶链反应评估OATP1B3 mRNA水平。利用Gd-EOB-DTPA增强MRI的信号强度计算肝胆期的相对增强(RE)。
免疫组织化学显示,LC-PBC患者中央静脉周围肝细胞中OATP1B3表达明显降低。LC-PBC患者肝脏OATP1B3 mRNA表达显著低于非LC-PBC患者(P < 0.05)。与非LC-PBC组(0.91±0.15,P < 0.01)和对照组(0.92±0.20,P < 0.01)相比,LC-PBC组MRI上的RE显著降低(0.33±0.14)。
Gd-EOB-DTPA增强MRI可能为LC-PBC患者的肝脏疾病提供一种有用的检测方法。