運用磁振造影技術定量分析肝臟功能性生物指標與膽道型態 — 臨床應用於膽道閉鎖患者與親屬活體肝臟捐贈者

Abstract

膽道閉鎖是一種先天性的疾病，至今成因仍未明，是一種持續性膽道纖維化的疾病。在我國發生率是3.7/10,000，相較於西方國家0.4~0.8/10,000的機率，明顯高出了許多。膽道閉鎖是阻塞性黃疸中最常見且最嚴重的原因，也是兒童肝臟移植最主要的原因。自從日本籍葛西醫師提出肝門脈腸道造口術之後，膽道閉鎖的存活率已大幅提高。早期診斷，早期手術，對此類病童的長期存活率有重要的影響。但即使接受了成公的手術治療，仍有一部分的存活者還是會持續肝硬化。長期會出現的併發症包括逆行性膽道炎和肝門脈高壓(如食道靜脈瘤出血、腹水、以及脾臟功能亢進等等)。 目前肝臟穿刺仍是評估肝臟硬化程度的黃金標準，但此程序有一定的危險性，同時存在局部組織的差異性和以局部推論整體的誤差。不具侵襲性的磁振造影常被用來追蹤和評估肝炎性肝硬化的進展程度。有數篇研究顯示，罹患肝炎性肝硬化之成人患者的肝臟表面擴散係數會比正常人的數值為低。加入白蛋白與丙氨酸氨基轉移酶所計算得到的擴散係數相關指標，將與肝功能有更明顯的相關性。雖然具有侵入性，目前術中膽道攝影仍然是顯示膽道構造變異的標準影像。 我們的研究首先企圖從接受過葛西氏手術的膽道閉鎖病患之臨床檢驗值和磁振造影影像中，找出實用且簡單的較不具侵入性的定量化影像指標，以預測患者是否會發生食道靜脈瘤的併發症。其次，我們企圖找出膽道閉鎖病患術後之肝臟硬化程度: 臨床肝功能檢驗值，Child-Turcotte(CT)或Child-Pugh(CP)積分，和pediatric end-stage liver disease (PELD)或model of end-stage liver disease (MELD)積分，與擴散權重磁振造影所得肝臟表面擴散係數及其相關指標之間的相關性。另外我們也設計了一連串的研究來比較磁振膽道造影與傳統術中膽道攝影的差異，並嘗試給予嗎啡與昇糖素等藥物來改善和增強活體肝臟捐贈者的磁振膽道造影之影像品質。 我們的實驗結果可以得到下列數個結論: (1)較不具侵襲性的磁振造影定量化影像指標能夠成功預測膽道閉鎖患者有無出現臨床明顯的食道靜脈瘤; (2)肝臟表面擴散係數及其相關指標能夠成功預測膽道閉鎖患者的肝硬化程度; (3)磁振膽道攝影的臨床應用不遜於術中膽道攝影; (4)嗎啡類藥物和昇糖素可以使活體肝臟捐贈者的磁振膽道攝影影像更清楚。

Biliary atresia (BA) is a congenital and progressively obliterative cholangiopathy of unknown etiology. The prevalence rate was about 3.7 in 10000 live births in Taiwan, much higher than western country (about 0.4 to 0.8 in 10000 live births). It is a major and severe cause of obstructive jaundice, also the leading indication for liver transplantation in pediatric population. After a Japanese surgeon, Kasai, reported a portoenterostomy operation for treatment, the long term survival rate has improved greatly. Earlier diagnosis and earlier operation improve the long term survival of biliary atresia. Progressive liver cirrhosis may persist in some patients even after successful operation. Long term complications include retrograde cholangitis, and portal hypertension including esophageal variceal bleeding, ascites and hypersplenism. Up to date, liver biopsy is still the golden standard of assessing the stages of cirrhosis. However, it has potential risk and is prone to regional sampling variability and error. Magnetic resonance imaging (MRI), a noninvasive imaging modality, was suggested to monitor progression of hepatitis-related cirrhosis periodically to assess the severity of liver cirrhosis. Several previous studies have shown a decrease in hepatic apparent diffusion coefficient (ADC) obtained from diffusion weighted image in patients with hepatitis-related liver cirrhosis compared with healthy control subjects. Incorporation of albumin and alanine transaminase into the ADC-related noninvasive indices may correlate with liver function further. MRI also plays an important role in the preoperative evaluation of the living related liver donors to reduce postoperative morbidity and complications. Though invasive, intraoperative cholangiography is still the golden standard in demonstrating anatomical variation of bile ducts. Firstly, we evaluated the validity of less-invasive quantitative imaging parameters for predicting the presence of clinically significant esophageal varices in BA patients. In addition, the values of hepatic ADC and ADC-related indices were applied to BA patients and correlated with cirrhotic severity scores of Child-Turcotte (CT) or Child-Pugh (CP) systems, and pediatric end-stage liver disease (PELD) or model of end-stage liver disease (MELD). We also design a serial studies to compare the difference between magnetic resonance cholangiopancreatography (MRCP) and intraoperative cholangiography, and to investigate the effectiveness of the combined use of intravenous morphine and intramuscular glucagon in improving MRCP image quality in donors for living-related liver transplantation. Our results may draw conclusions including: (1) less-invasive quantitative imaging parameters can predict the presence of clinically significant esophageal varices in BA patients; (2) the values of hepatic ADC and ADC-related indices can predict the cirrhotic severity of BA patients and negatively correlated with clinical cirrhotic severity score systems; (3) MRCP is comparable to intraoperative cholangiography in clinical usage; (4) combined usage of morphine and glucagon can improve MRCP image quality in donors for living-related liver transplantation.