Biliary atresia (BA) is an inflammatory, progressive

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1 Effects of the Infant Stool Color Card Screening Program on 5-Year Outcome of Biliary Atresia in Taiwan Tien-Hau Lien, 1 Mei-Hwei Chang, 1 Jia-Feng Wu, 1 Huey-Ling Chen, 1 Hung-Chang Lee, 2 An-Chyi Chen, 3 Mao-Meng Tiao, 4 Tzee-Chung Wu, 5 Yao-Jong Yang, 6 Chieh-Chung Lin, 7 Ming-Wei Lai, 8 Hong-Yuan Hsu, 1 Yen-Hsuan Ni, 1 and the Taiwan Infant Stool Color Card Study Group* In Taiwan, a screening system using an infant stool color card to promote the early diagnosis of biliary atresia (BA) was established in This study aimed to investigate the 5-year outcome of BA before and after using the screening program. BA patients were divided into three cohorts according to their birth dates. The patients in cohort A (n 5 89) were born before the stool card screening program ( ); those in cohort B (n 5 28) were screened by the stool card regional screening program ( ); and those in cohort C (n 5 74) were screened by the stool card universal screening program ( ). The relative odds ratios were computed using logistic regression to compare the different factors affecting survival time. The rate of age at Kasai operation <60 days was 49.4% and 65.7% in cohorts A and B1C, respectively (P ). The jaundice-free (total serum bilirubin <2.0 mg/dl) rate 3 months after surgery was 34.8% and 60.8% in cohorts A and B1C, respectively (P < 0.001). The 3-year jaundice-free survival rate with native liver was 31.5% in cohort A and 56.9% in cohort B1C (P < 0.001), whereas the 3-year overall survival rates were 64.0% and 89.2%, respectively (P < 0.001). The 5-year jaundice-free survival rate with native liver was 27.3% in cohort A and 64.3% in cohort B (P < 0.001), and the 5-year overall survival rates were 55.7% and 89.3%, respectively (P < 0.001). Conclusion: The stool color card screening program for BA allows for earlier Kasai operation, which increases the jaundice-free rate at 3 months postsurgery. With higher surgical success rates, the 3- and 5-year outcome of BA patients in Taiwan improves remarkably. (HEPATOLOGY 2011;53: ) Biliary atresia (BA) is an inflammatory, progressive fibro-sclerosing cholangiopathy of infancy that variably affects both the extrahepatic and intrahepatic bile ducts, 1,2 resulting in the destruction and obstruction of the biliary tract. 2-4 If untreated, BA progresses to cirrhosis with portal hypertension and liver failure leading to death within 2 to 3 years. Since the Kasai operation was first used for BA in 1959, there have been encouraging results in treating this disease such that it has become the first-line treatment. The Kasai operation can restore bile flow through a reconstructed hepatic portoenterostomy to a jejunal loop. Once the cholestasis progresses and/or complications of liver cirrhosis occur, liver transplantation remains the salvage way for BA. Although ongoing cholestasis, which further aggravates liver cirrhosis, is present in most BA children, 5 a successful Kasai operation may still delay or even decrease the need for liver transplantation. Abbreviations: BA, biliary atresia; CI, confidence interval; OR, odds ratio. From the 1 Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; the 2 Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan; the 3 Department of Pediatrics, China Medical University Hospital, Taichung, Taiwan; the 4 Department of Pediatrics, Chang Gung Memorial Hospital- Kaohsiung Medical Center, Kaohsiung, Taiwan; the 5 Department of Pediatrics, Taipei Veterans General Hospital & National Yang Ming University, Taipei, Taiwan; the 6 Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan; the 7 Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan; and the 8 Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan. Received May 4, 2010; accepted September 22, Supported by grants of the Bureau of Health Promotion of the Department of Health, Taiwan (Project No A). The members of the Taiwan Infant Stool Color Card Study Group are: Wan-Hsin Wen (Cardinal Tien Hospital), Chun-Hsien Yu (Taipei City Hospital, Branch for Women and Children), I-Hsien Lee (Changhua Christian Hospital), Lung-Huang Lin (Cathay General Hospital), Wen-Terng Lin (En Chu Kong Hospital), Hsiang-Hung Shih (Kaohsiung Medical University), Pi-Feng Chang (Far Eastern Memorial Hospital), Ching-Feng Huang (Tri-Service General Hospital), I-Fei Huang (Kaohsiung Veterans General Hospital), Chun-Yan Yeung (Mackay Memorial Hospital, Tamshui Branch), Shan-Ming Chen (Chung Shan Medical University Hospital), and Te-Kuei Hsieh (Hsin Chu General Hospital, Department of Health, Executive Yuan). 202

2 HEPATOLOGY, Vol. 53, No. 1, 2011 LIEN ET AL. 203 It is generally accepted that the Kasai operation is more successful in children when performed earlier than 60 days of age. 6,7 The reported successful bile flow rates were 91%, 56%, 38%, and 17% in patients receiving an operation before 60 days of age, at days of age, at days of age, and beyond 90 days of age, respectively. 8 However, early identification and timely surgery, which are crucial for better prognosis, remain challenging. In Taiwan, a pilot regional study using the infant stool color card to increase the efficacy of early identification of BA was started in Universal screening for BA using the infant stool color card was launched in This is the first nationwide screening program for BA using an infant stool color card. The present study aimed to compare the outcome of the BA patients after Kasai operation before versus after the launch of the infant stool color card screening program. Patients and Methods Infant Stool Color Card. An infant stool color card was designed with six photographs of different colored stool samples from Taiwanese infants. Three colors on this card were labeled abnormal (clay-colored, pale yellowish, and light yellowish), whereas the other three were labeled normal (yellowish, brown, and greenish). Telephone and fax numbers for consultation were also printed on this card, and parents, guardians, and medical personnel were instructed to inform the stool card registry center if abnormal stool colors were noticed. There are professional personnel in the stool card center who respond to every related phone call or fax within 24 hours. Instructions and follow-up were given to every reported case. In 2002, 47,180 newborns from 49 hospitals and clinics in northern and central Taiwan were enrolled. In 2003, the range of cooperation extended to southern and eastern Taiwan, and 72,793 newborns from 96 hospitals were enrolled. In 2004, the universal stool color screening program was launched, and the stool color card was integrated into the child health booklet. All neonates born in Taiwan participated in the screening program since then. Patients. All of the patients had a diagnosis of BA made using clinical data, biochemical data, imaging data, surgical findings, and liver histology. The patients were divided into three cohorts by their birth date. The historical control cohort was derived from the 96 cases diagnosed as BA at the National Taiwan University Hospital from January 1990 to December Five patients who did not receive Kasai operation and two patients who underwent Kasai operation but were not followed up for at least 3 years postoperatively were excluded. The remaining 89 patients became cohort A. All of these patients were followed up for at least 5 years, except one patient who was followed up for only 3 years postoperatively. Cohort A represented patients born before the stool card screening program. There were 29 BA patients born between 2002 and One patient who did not receive Kasai operation was excluded. The other 28 patients who were followed up for at least 5 years postoperatively were enrolled in cohort B, which represented the period of the regional pilot study of the stool card screening program in Taiwan. Seventy-five BA patients were born between 2004 and After excluding one patient without Kasai operation, the 74 patients who were followed up for at least 3 years postoperatively were enrolled in cohort C, which represented the nationwide screening data in Taiwan. Cohort BþC was the merged data of cohorts B and C and represented the era of the stool color card screening program. Statistical Methods and Data Analysis. Statistical analyses were performed using Stata software (Stata- Corp LP, College Station, TX). A chi-square test was used to compare categorical variables, including age at Kasai operation <60 days, jaundice-free rates at 3 months after Kasai operation, 3- and 5-year survival rates with native liver, 3- and 5-year jaundice-free survival rates with native liver, and 3-year and 5-year overall survival rates between different cohorts. Overall survival included those patients who survived with either their native liver or a transplanted liver. Jaundice-free was defined as total serum bilirubin <2.0 mg/dl (34 lmol/l). Quality outcome was defined as jaundice-free survival with native liver. All survival time was calculated after the date of the Kasai operation. Relative odds ratios were computed using logistic regression models to compare the different factors affecting survival time. The Kaplan-Meier method and a log-rank test were also used to assess factors affecting survival. P < 0.05 was considered statistically significant. Address reprint requests to: Mei-Hwei Chang, M.D., Department of Pediatrics, National Taiwan University Hospital, No. 7, Chung-Shan S. Rd., Taipei, 100, Taiwan. changmh@ntu.edu.tw; Fax: (886) Copyright VC 2010 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI /hep Potential conflict of interest: Nothing to report. Additional Supporting Information may be found in the online version of this article.

3 204 LIEN ET AL. HEPATOLOGY, January 2011 From 1990 until now, there was no systemic change in post-kasai operation care except for the concept of prophylactic antibiotics use in Taiwan. Since 1997, most patients have been prescribed with prophylactic antibiotics after operation. The data of the use of prophylactic antibiotics are collected by chart review, and this possible confounding factor is taken into consideration for analyses. The regimen of prophylactic antibiotics is trimethoprim-sulfamethoxazole (TMP-SMZ, 7 days per week) or neomycin (4 days per week). Our previous study reveals the superior effect of using prophylactic antibiotic versus not using it, and the equal effect for the prophylaxis of cholangitis between the two antibiotic regimens. 9 Results Comparisons of Cohort A versus Cohort (B1C). There was no significant difference in the sex distribution between cohort A and cohort (BþC). The rates of Kasai operation performed before 60 days of age were 49.4% in cohort A and 65.7% in cohort BþC (P ¼ 0.02). At 3 months after Kasai operation, the jaundice-free rate was significantly higher in cohort BþC than in cohort A (60.8% versus 34.8%; P < 0.001). The 3-year survival rates with native liver in cohort A and cohort BþC were 51.7% and 61.8%, respectively. The 3-year jaundice-free survival rate with native liver was significantly higher in cohort BþC than in cohort A (56.9% versus 31.5%; P < 0.001). The 3-year overall survival rate was 64.0% in cohort A and 89.2% in cohort BþC (P < 0.001). The 5-year follow-up was not yet finished in cohort C; therefore, only cohort B was compared with cohort A in the analyses of 5-year survival time. The 5-year survival rates with native liver in cohorts A and B were 37.5% and 64.3%, respectively (P ¼ 0.01). The 5-year jaundice-free survival rate with native liver was significantly higher in cohort B than in cohort A (64.3% versus 27.3%; P < 0.001) and the 5-year overall survival rates were 89.3% and 55.7%, respectively (P < 0.001). However, 15 cases in cohort BþC, despite their birth after the launch of the stool card screening program, were not successfully screened using the stool card. In order to clearly demonstrate the effect of the stool card screening program, we further analyzed the outcome by redividing our total cases from 1990 to 2005 into two groups for comparison: one group representing BA children without the screening program or not screened out by the stool card, the other group representing BA children who benefited from stool Table 1. General Characteristics and Outcomes in Cohort A versus Cohort B1C Cohort A (n 5 89)* Cohort B1C (n )y P Value Male sex 38 (42.7) 56 (54.9) 0.09 Age 60 days at 44 (49.4) 67 (65.7) 0.02 Kasai operation Jaundice-free 31 (34.8) 62 (60.8) < months after Kasai operation Survival 3-year SNL 46 (51.7) 63 (61.8) year JFSNL 28 (31.5) 58 (56.9) < year OS 57 (64.0) 91 (89.2) < year SNL 33 (37.5) 18 (64.3) year JFSNL 24 (27.3) 18 (64.3) < year OS 49 (55.7) 25 (89.3) <0.001 Data are expressed as No. (%). Abbreviations: JFSNL, jaundice-free survival with native liver, OS, overall survival; SNL, survival with native liver. *Includes patients born before the institution of the stool color card screening program ( ). The data of cohort B and cohort C were merged to represent the outcomes in the era of the stool color card screening program. Cohort B (n ¼ 28) includes patients born during the regional study of the stool color card screening program ( ). Cohort C (n ¼ 74) includes patients born after the launch of the nationwide study of the stool color card screening program ( ). Total serum bilirubin <2.0 mg/dl. One patient was lost to follow-up. Only 88 patients completed the 5-year follow-up. Only cohort B (n ¼ 28) was followed up for more than 5 years and calculated in this data. card screening (Supplement Table 1). The results are similar to the comparisons of cohort A and cohort BþC (Table 1). Jaundice-Free at 3 Months After Kasai Operation. Logistic regression analyses revealed that patients who underwent Kasai operation before 60 days of age had a higher jaundice-free rate at 3 months after surgery compared with those who underwent surgery after 60 days of age (odds ratio [OR] 2.62; P ¼ 0.001) (Table 2). Patients born in the stool card screening era (cohort BþC) had a significantly higher jaundice-free rate at 3 months postsurgery than patients born before the screening era (cohort A) (OR 2.90; P < 0.001). Survival with Native Liver The 3-year survival rates with native liver in patients who received Kasai operation before 60 days of age and after 60 days of age were 64.9% and 46.3%, respectively (OR 2.15; 95% confidence interval [CI] ; P ¼ 0.01). The 5-year survival rates with native liver in patients who underwent surgery before 60 days old and after 60 days old were 55.0% and 32.1%, respectively (OR 2.58; 95% CI ; P ¼ 0.01). The 3-year survival rates with native liver in patients who were and were not jaundice-free at 3 months after Kasai

4 HEPATOLOGY, Vol. 53, No. 1, 2011 LIEN ET AL. 205 Table 2. Factors Affecting Jaundice-Free Status 3 Months After Kasai Operation in Patients with BA Jaundice-Free* 3 Months After Kasai Operation OR (95% CI) P Value Age at Kasai operation days 65/111 (58.6%) 2.62 ( ) >60 days 28/80 (35%) 1.00 Stool card program <0.001 Cohort BþC 62/102 (60.8%) 2.90 ( ) Cohort A 31/89 (34.8%) 1.00 *Total serum bilirubin <2.0 mg/dl. The data of cohort B and cohort C were merged to represent the outcomes in the era of the stool color card screening program. Cohort B (n ¼ 28) includes patients born during the regional study of the stool color card screening program ( ). Cohort C (n ¼ 74) includes patients born after the launch of the nationwide study of the stool color card screening program ( ). Cohort A (n ¼ 89) includes patients born before the institution of the stool color card screening program ( ). operation were 84.9% and 30.6%, respectively (OR 12.79; 95% CI ; P < 0.001). The 5-year survival rates with native liver in patients who were and were not jaundice-free at 3 months postsurgery were 77.6% and 19.4%, respectively (OR 14.35; 95% CI ; P < 0.001). Jaundice-Free Survival with Native Liver. Jaundice-free survival with native liver was considered as quality outcome. Cohort BþC had higher rates of 3- and 5-year jaundice-free survival with native liver than cohort A (OR 2.87, P ¼ 0.001, and OR 4.80, P ¼ 0.001, respectively) (Table 3). Patients who received Kasai operation before 60 days of age had better 3- and 5-year jaundice-free survival with native liver than patients who received an operation after 60 days of age (OR 3.25, P < and OR 2.63, P ¼ 0.02, respectively). Patients who had used prophylactic antibiotics had better 3- and 5-year jaundice-free survival with native liver than patients who had not (OR 3.03, P ¼ and OR 2.79, P ¼ 0.01, respectively). Moreover, patients who were jaundice-free at 3 months postsurgery had better 3- and 5-year jaundice-free survival with native liver than those who were not jaundice-free (OR 39.34, 95% CI , P < and OR 21.43, 95% CI , P < 0.001, respectively). Sex did not affect outcome. Intervention by the stool card screening program, Kasai operation before 60 days of age, the use of prophylactic antibiotics, and jaundice-free at 3 months postsurgery were the predictors of quality outcome for BA patients. Overall Survival. Cohort BþC had better 3- and 5-year overall survival rates than cohort A (OR 4.64, P < and OR 6.63, P ¼ 0.003, respectively) (Figs. 1 and 2; Table 4). Patients who had used prophylactic antibiotics had better 3- and 5-year overall survival rates than those who did not (OR 5.33, P < and OR 6.31, P < 0.001, respectively). Those who were jaundice-free at 3 months after Kasai operation had better 3- and 5-year overall survival rates than those who were not jaundice-free (OR 11.15, P < and OR 10.85, P < 0.001, respectively). Discussion Biliary atresia (BA) is an obliterative cholangiopathy of unknown etiology. It is the most common cause of Table 3. Jaundice-Free Survival with Native Liver in Patients with BA 3-Year Jaundice-Free* Survival with Native Liver OR (95% CI) P Value 5-Year Jaundice-Free Survival with Native Liver OR (95% CI) P Value Age at Kasai operation < days 63/111 (56.8%) 3.25 ( ) 28/60 (46.7%) 2.63 ( ) >60 days 23/80 (28.8%) /56 (25%) 1.00 Stool card program Cohort BþC 58/102 (56.9%) 2.87 ( ) 18/28 (64.3%) 4.80 ( ) Cohort A 28/89 (31.5%) /88 (27.3%) 1.00 Prophylactic antibiotics Used 70/132 (53.0%) 3.03 ( ) 30/65 (46.2%) 2.79 ( ) No use 16/59 (27.1%) /51 (23.5%) 1.00 Sex Male 45/94 (47.9%) 1.25 ( ) 21/54 (38.9%) 1.24 ( ) Female 41/97 (42.3%) /62 (33.9%) 1.00 *Total serum bilirubin <2.0 mg/dl. The data of cohort B and cohort C were merged to represent the outcomes in the era of the stool color card screening program. Cohort B (n ¼ 28) includes patients born during the regional study of the stool color card screening program ( ). Cohort C (n ¼ 74) includes patients born after the launch of the nationwide study of the stool color card screening program ( ). Cohort A (n ¼ 89) includes patients born before the institution of the stool color card screening program ( ). Only 88 patients completed the 5-year follow-up.

5 206 LIEN ET AL. HEPATOLOGY, January 2011 Fig. 1. The 5-year overall survival rates in cohort B (dotted line), which represents the era of stool color card screening program, and in cohort A (solid line), which represents the era before the stool color card screening program, were 89.3% and 55.7%, respectively (P ¼ 0.002). end-stage liver disease in children, with an incidence of 0.51 per 10,000 in France, per 10,000 in the United Kingdom, per 10,000 in Sweden, 12 and 0.85 per 10,000 in North America. 12 There is a higher incidence in Asia, including 1.04 per 10,000 in Japan 13,14 and 1.78 per 10,000 in Taiwan. 7 Taiwan is one of the areas with the highest incidence in the world. Kasai operation is the primary surgical therapy for BA, even in the era of liver transplantation. 15 Survival of BA patients with their native liver relies mainly on the success of the Kasai operation, 16 which is correlated with age at surgery. 13 In the Swiss national study, year survival with native liver is 75% in patients who receive the Kasai operation before 46 days, 33% in patients receiving the operation between 46 and 75 days, and 11% in patients receiving the operation after Fig. 2. The 5-year overall survival rates in subjects who were jaundice-free (dotted line) versus those who were not jaundice-free (solid line) at 3 months after Kasai operation was 89.8% and 44.8%, respectively (P < 0.001). 75 days (P ¼ 0.02). In long-term follow-up, the 20- year survival with native liver is significantly better in patients who receive the operation before the age of 90 days than in those who receive it after 90 days (28% versus 13%; P ¼ 0.006). 5 In the current study, patients who underwent Kasai operation before the age of 60 days had significantly better survival with native liver than those receiving the operation after 60 days of age. The earlier age at Kasai operation is indeed an important predictive factor of better long-term survival with native liver. For early diagnosis of BA, the stool card screening program was started in Taiwan in regional areas in 2002 and extended nationwide in The rate of children with Kasai operation before 60 days of age significantly improved in the stool card screening era. Table 4. Overall Survival with or Without Liver Transplantation in Patients with BA 3-Year Overall Survival OR (95% CI) P Value 5-Year Overall Survival OR (95% CI) P Value Age at Kasai operation days 89/111 (80.2%) 1.44 ( ) 42/60 (70%) 1.75 ( ) >60 days 59/80 (73.8%) /56 (57.1%) 1.00 Stool card program < Cohort BþC* 91/102 (89.2%) 4.64 ( ) 25/28 (89.3%) 6.63 ( ) Cohort A 57/89 (64.0%) /88 (55.7%) 1.00 Prophylactic antibiotics <0.001 <0.001 Used 115/132 (87.1%) 5.33 ( ) 53/65 (81.5%) 6.31 ( ) No use 33/59 (55.9%) /51 (41.2%) 1.00 Sex Male 76/94 (80.9%) 1.47 ( ) 37/54 (68.5%) 1.47 ( ) Female 72/97 (74.2%) /62 (59.7%) 1.00 *The data of cohort B and cohort C were merged to represent the outcomes in the era of the stool color card screening program. Cohort B (n ¼ 28) includes patients born during the regional study of the stool color card screening program ( ). Cohort C (n ¼ 74) includes patients born after the launch of the nationwide study of the stool color card screening program ( ). Only cohort B was followed up longer than 5 years and calculated in 5-year survival analyses. Cohort A (n ¼ 89) includes patients born before the institution of the stool color card screening program ( ). Only 88 patients completed the 5-year follow-up.

6 HEPATOLOGY, Vol. 53, No. 1, 2011 LIEN ET AL. 207 The 3-year survival rate with native liver in the era before the stool card screening program was 51.7%, which increased to 61.8% in the stool card screening era (Table 1). Why is this improvement not as evident as expected? Persistent and/or progressive jaundice is usually the first alarm of impaired bile flow and progressive liver cirrhosis. In the years before the stool card screening program, the skills and care involved in liver transplantation were not as fully developed as they are now. Moreover, the concept of a living-related donor had not yet been accepted by the general population. The requirement and timing of liver transplantation was therefore more conservative and delayed. Some patients, however, lived with their native liver despite severe jaundice-related complications. In the era of the stool card screening program, liver transplantation has become more polished and has gained more social acceptance. Pediatricians and surgeons in recent years have preferred to choose an appropriate but earlier timed liver transplantation for those patients with persistent jaundice, before many complications occur. Hence, the 3-year survival rate with native liver in the stool card screening era is only slightly better than that of the era without screening. As time goes by, fewer and fewer patients can survive without transplantation if their jaundice is persistent. In the analyses of 5-year survival with native liver, those born in the stool card screening era already show significantly better results. We believe that jaundice-free survival rate with native liver can reflect the true outcome of BA without the interference of liver transplantation during time change. Our study defined patients who had jaundice-free survival with native liver as a quality outcome. In our analyses, we found that use of the stool card screening program and Kasai operation before 60 days of age both contribute to quality outcome in BA patients. In the study by Shneider et al., 17 jaundice-free at 3 months after Kasai operation is an excellent predictor of 2-year survival with native liver. In the current study, patients who were jaundice-free at 3 months postsurgery had significantly higher survival rates with native liver and overall survival rates, as well as more quality outcome in both the 3- and 5-year analyses. Jaundice-free at 3 months after Kasai operation can be an indicator for successful surgery and a valuable predictor of 5-year outcome. In the analyses here, jaundice-free at 3 months after surgery is significantly correlated with the implementation of the stool card screening program and earlier age at surgery. Although the timing of abnormal stool presented is different in each case of biliary atresia, the stool color card alerts the parents, medical personnel, and guardians to find BA patients and send them for Kasai operation earlier when their hepatic damage is milder. Our data indeed supports that BA patients born in the era of stool card screening program have significantly better quality outcome than those born before the era. Overall survival is significantly better in the era of the stool card screening program. Other studies show that the better the results of the Kasai operation, the better the overall survival. 16,18 Although more developed transplantation techniques in the stool card screening era partly contribute to survival, the need for liver transplantation still adds risk to impair the prognosis. Successful Kasai operation still provides patients with the best chance of survival, and every effort should be made to improve its results. 16 The stool card screening program is a step in this direction, because it efficiently increases the success rate of Kasai operation and contributes to better overall survival. The 5-year survival rate with native liver and 5-year overall survival rate in other studies range from 30.1% to 59.7% and from 75.5% to 85%, respectively. 13,19,20 In Taiwan, these rates are 64.3% and 89.3%, respectively (Table 1). This corroborates the promising results of intervention using the stool card screening program. In conclusion, the stool card screening program for BA enhances early Kasai operation and increases the jaundice-free rate at 3 months postsurgery, which is a valuable predictor of 5-year outcome. In Taiwan, the infant stool color card screening program has markedly improved the 5-year outcome of BA patients. Acknowledgments: We appreciate the valuable contribution of the members of the Taiwan Infant Stool Color Card Study Group and thank Li-Chin Fan, Cheng-Hui Hsiao, Yu-Ru Tseng, and Szu-Ta Chen for assistance in preparing this article. References 1. Landing BH. Considerations of the pathogenesis of neonatal hepatitis, biliary atresia and choledochal cyst the concept of infantile obstructive cholangiopathy. Prog Pediatr Surg 1974;6: Bassett MD, Murray KF. Biliary atresia recent progress. J Clin Gastroenterol 2008;42: Kahn E. Biliary atresia revisited. Pediatr Dev Pathol 2004;7: Kobayashi H, Stringer MD. Biliary atresia. Semin Neonatol 2003;8: Lykavieris P, Chardot C, Sokhn M, Gauthier F, Valayer J, Bernard O. Outcome in adulthood of biliary atresia: a study of 63 patients who survived for over 20 years with their native liver. HEPATOLOGY 2005;41: Ohi R. Surgery for biliary atresia. Liver 2001;21: Hsiao CH, Chang MH, Chen HL, Lee HC, Wu TC, Lin CC, et al. 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