台灣嬰兒大便卡全國性篩檢膽道閉鎖之成果

UNIVERSAL INFANT STOOL COLOR CARD SCREENING PROGRAM FOR BILIARY ATRESIA IN TAIWAN: AN UPDATE

盧芳廷(Fang-Ting Lu)

指導教授 ： 張美惠

國立臺灣大學/醫學院/臨床醫學研究所/碩士(2017年)

https://doi.org/10.6342/NTU201703237

摘要

研究背景
膽道閉鎖是兒童肝病最常見的死因，也是兒童換肝的主因。若能早期診斷並早期接受葛西手術，術後膽汁流通率高，可改善長期預後。膽道閉鎖早期症狀為持續黃疸不退及灰白色大便。為了有效提高早期診斷率，台灣自2004年開始施行世界首創全國性嬰兒大便卡篩檢，自2009年起又推行新版九色大便卡(比舊版新增三色異常大便以供比對)，以期能增進灰白便辨識度，提高早期診治率、開刀率以及整體預後。

研究設計
這是一個前瞻性世代研究，評估使用新版九色大便卡篩檢膽道閉鎖的成效，並和過去無使用大便卡時期以及舊版六色大便卡篩檢成果做比較。本研究也分析過去13年來台灣膽道閉鎖病童預後，並分析一開始延遲手術的原因，以期找出延遲診斷的癥結點。

研究結果
根據台灣嬰兒大便卡中心2004年初至2016年底所登錄的全國膽道閉鎖資料庫，共有423位膽道閉鎖確診病童納入研究。另外1990年至2000年於台大醫院診斷的膽道閉鎖病童共89位，定義為無使用嬰兒大便卡之世代；2004年到2008年出生之病童，使用傳統六色大便卡，共有157位；2009年到2016年出生者使用新版九色大便卡，共有266位。使用大便卡篩檢後，六十日內接受葛西手術的比例在六色大便卡世代是63.7%，九色大便卡世代為65.0%，皆高於未使用大便卡世代(49.4 %)，有統計學上顯著差異。術後三個月黃疸消退率在使用大便卡兩個世代都接近六成，顯著高於先前未使用大便卡世代(34.8 %)。使用全國性大便卡篩檢後，病童的三年及五年原肝存活率分別為59.1%及58.3%，三年及五年無黃疸原肝存活率分別為55.1%及54.8%。回顧13年的研究，膽道閉鎖兒童的換肝率為31%，總存活率則為87 %。
針對兒科醫護同仁使用大便卡經驗，問卷統計顯示有96%的第一線兒科醫師認為九色大便卡有利於篩檢嬰兒膽道閉鎖與膽汁滯留症，但有15%覺得即使換成九色大便卡仍有辨色困難。針對超過六十日延遲開刀的原因分析，42 %病人肇因於缺乏完整的檢驗合併家屬對疾病徵兆的忽視。

結論
我國自2004年起推行全國性大便卡篩檢，無論使用六色或是九色大便卡，對膽道閉鎖早期診斷、早期開刀及術後黃疸消退率，都有良好的成效。病人存活率以及總存活率皆優於歐美各國成果。為了再提高六十天內開刀率，除了現行使用大便卡篩檢，必須加入其他篩檢工具輔助，並致力於推廣認知教育（包括對第一線兒科醫護人員安排繼續教育訓練以確保篩檢能力，以及民眾端有關嬰兒延遲性黃疸的認知），以期改進我國延遲診斷的比例。

關鍵字

膽道閉鎖 ； 嬰兒大便卡 ； 預後 ； 葛西手術

並列摘要

Objective
Biliary atresia (BA) is a progressive obliterated cholangiopathy, resulting in bile flow obstruction and further biliary cirrhosis. It presents as clay color stool with persistent cholestasis in the early infancy and it is the leading cause of pediatric liver transplantation. A good outcome of the patients depends on early diagnosis and timely successful Kasai operation (hepatic porto-enterostomy). To enhance early diagnosis, the first widespread infant stool color (6-color) screening program in the world had been launched in Taiwan since 2004. A new 9-color stool card was developed in 2009 to enhance the recognition and timely diagnosis.
Study designs
In this prospective cohort study, we investigated the application and effectiveness of the new 9-color stool color card in the early diagnosis of biliary atresia and long-term outcome. We compared that with the era without using stool color card or with the original 6-color card. Besides, we also review the major causes of delay Kasai operation to promote early diagnosis rate.
Results
Totally 423 patients of definite BA were included from the database of Infant Stool Card Registry Center of Taiwan between Jan. 2004 to Dec.2016. 157 infants born in 2004 -2008 used the original 6-color stool cards, and the other 266 infants born in 2009-2016 used the new 9-color card. We also enrolled 89 BA children who were diagnosed as BA in NTUH in 1990-2000 without using stool color card for screening. The proportion of age at Kasai procedure before 60 days in 6-colored (63.7%) and 9-colored (65.0%) was both significantly higher than those without using stool color card (49.4%) (p <0.01). Comparing 6-color or 9-color card revealed equally good screening effectiveness. Jaundice free rate (total bilirubin < 2 mg/dL) of these 2 groups were both almost 60% also significantly better than the group no use stool color cards (34.8 %). In the series of using stool color card for screening for 13 years, 3-years and 5-years native liver survival rate was 59.1% and 58.3%, and 3-years and 5-years jaundice-free native live survival rate was 55.1% and 54.8%. Overall survival rate in 5 years was 88%. In this 13-year study, overall survival rate was 87 % and the rate of liver transplantation was 31%.
Early referral, early operation, and jaundice-free at 3 months after Kasai surgery were associated with a greater predictor of native liver survival. Up to 96% of our pediatric doctor regarded stool color card as a useful screen tool for screen biliary atresia, but still 15% doctors had indeterminate result in the recognition of abnormal stool color even used current 9-colored stool card. The analysis of cause for delayed Kasai operation showed 42 % patients had cognitive insufficiency of caregiver combined with an inadequate screen of cholestasis.
Discussion and Conclusions
The early Kasai Surgery rate and jaundice free rate in children with biliary atresia had been effectively improved after the extensive promotion of the universal stool color card screening program in Taiwan, using either 6-color cards or 9-color stool cards. The overall survival and native liver survival were improved and superior. However, we still need other screen tools to assist stool color card screening program to promote the early diagnosis rate. Besides, it is also necessary to continue to promote educational programs for the awareness for biliary atresia to the family and the healthcare professionals to enhance better outcome.

並列關鍵字

Biliary atresia ； infant stool color card ； prognosis ； Kasai operation

參考文獻

Asai, A., Miethke, A., & Bezerra, J. A. (2015). Pathogenesis of biliary atresia: defining biology to understand clinical phenotypes. Nat Rev Gastroenterol Hepatol, 12(6), 342-352.

Chardot, C., Buet, C., Serinet, M. O., Golmard, J. L., Lachaux, A., Roquelaure, B., . . . Jacquemin, E. (2013). Improving outcomes of biliary atresia: French national series 1986-2009. J Hepatol, 58(6), 1209-1217.

Chen, S. M., Chang, M. H., Du, J. C., Lin, C. C., Chen, A. C., Lee, H. C., . . . Chen, H. L. (2006). Screening for biliary atresia by infant stool color card in Taiwan. Pediatrics, 117(4), 1147-1154.

Chiu, C.-Y., Chen, P.-H., Chan, C.-F., Chang, M.-H., & Wu, T.-C. (2013). Biliary Atresia in Preterm Infants in Taiwan: A Nationwide Survey. The Journal of Pediatrics, 163(1), 100-103.e101.

Davenport, M. (2012). Biliary atresia: clinical aspects. Seminars in Pediatric Surgery, 21(3), 175-184.