Use of stool color card as screening tool for biliary atresia in resource-constraint country.

Aim: The study was aimed to find out the efficacy of a stool color card (SCC) in differentiating biliary atresia (BA) from non-BA in resource-limited countries. Background: stool color screening system was introduced in 2004 which lead to marked improvement in sensitivity of detecting BA. Methods: This cross-sectional observational study was conducted from January, 2019 through July, 2022 on purposively sampled infants who developed jaundice before three months of age, had direct bilirubin of > 20 % of total with pale stool and dark urine. Results: 144 cases (male, 96) were included in the study and their mean age at admission was 87.3±37.2 days and mean age at onset of jaundice was 6.1±7.7 days. BA was confirmed in 106 (73.6%) cases and 38 (26.4%) children were in non-BA group. Frequency of persistent pale stool between BA and non- BA were 88 vs 8 (83.0 % Vs 21.0 %) which was highly significant (p=0.000). Mean difference of total and direct serum bilirubin, median alanine transferase and alkaline phosphatase were not statistically significant between two groups. Median of serum gamma glutamyl transpeptidase (GGT) in BA was 570 U/L and in non-BA it was 138.0 U/L which was statistically significant (p=0.000). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of SCC were 83%, 78.9%, 91.7%, 62.5% and 81.9% respectively. Conclusion: SCC has good sensitivity to diagnose BA but failed to prove better specificity to rely simply on it. SCC may be used as early screening tool for prompt referral to appropriate medical care centers for final evaluation of BA.

Cost-Effectiveness Analysis of Universal Screening for Biliary Atresia in Japan.

OBJECTIVE: To evaluate the cost-effectiveness of universal newborn screening using stool color card or direct bilirubin (DB) testing when comparing with no screening for biliary atresia in Japanese setting. STUDY DESIGN: A decision analytic Markov microsimulation model was developed to evaluate the universal screening for biliary atresia. Our screening strategies included stool color card, DB, or no screening. The outcomes of all newborns undergoing 3 strategies were simulated to analyze event-free life-years defined as liver transplant-free survival, costs, and incremental cost-effectiveness ratio (ICER) over a 25-year period with an annual discount rate of 2% applied for both costs and outcomes. A 1-way sensitivity analysis was performed to assess the uncertainty. RESULTS: There were 941 000 newborn infants in our cohort and 114 cases of biliary atresia. The base case analysis showed that the stool color card strategy was $14 927 337 higher than no screening with an increase in 44 more event-free life-years gained, resulting in an ICER of $339 258 per event-free life-year gained. The DB screening strategy compared with stool color card was $138 994 060 higher with an increase in 271 more event-free life-years gained and an ICER of $512 893 per event-free life-year gained. The DB screening strategy compared with no screening resulted in an ICER of $488 639 per event-free life-year gained. The DB screening resulted in 16 fewer liver transplants than stool color card and stool color card had 2 fewer liver transplants than no screening. CONCLUSIONS: Universal screening for biliary atresia could be cost-effective depending on the willingness to pay thresholds for health benefits.

¿Reconocemos adecuadamente la acolia/ hipocolia en los lactantes?

Objetivo: El objetivo de este estudio fue valorar el nivel de acierto del personal de salud en la identificación de hipocolia/acolia en un escenario simulado. Con respecto a esto afirmamos que la hipocolia/acolia son signos clínicos que indican obstrucción biliar, relacionándose con enfermedades colestásicas obstructivas, siendo la atresia de vías biliares una de las principales causas en los primeros meses de vida; en esta, el pronóstico del manejo quirúrgico depende del diagnóstico temprano. Métodos: Estudio descriptivo/ prospectivo basado en la realización de una prueba virtual al personal de salud de Medellín, dividiéndose según sitio de trabajo, edad, sexo y profesión. Fueron utilizadas cinco imágenes de la tabla de colores de materia fecal, utilizada en Taiwán, previa autorización de sus autores. Se consideró reconocimiento adecuado cuando el participante identificaba como anormales las tres imágenes que representaban la acolia/hipocolia. Resultados: Se obtuvo respuesta de 442 participantes (se excluyeron 53) y solo 253 (65 %) lograron reconocimiento adecuado. En el análisis por subgrupos se encontró que hubo un mayor acierto en los participantes del Hospital Pablo Tobón Uribe con respecto a otras instituciones (69 y 54.6 %, respectivamente - p. 0.005). Los participantes con menor porcentaje de acierto fueron los médicos generales en un (45 %). Conclusión: Durante la valoración simulada sobre la identificación adecuada de acolia/hipocolia se encontró que solo el 65 % de la población participante acertó en la identificación correcta de este signo clínico, lo que sugiere una mayor atención en cuanto al entrenamiento para la identificación de acolia/hipocolia.

Objetive: The objective of this study was to assess the level of success of healthcare worker in the identification of hypocholia / acholia in a simulated scenario. With respect to this, we affirm that hypocholia/acholia are clinical signs indicative of biliary obstruction, related to obstructive cholestatic diseases, being bile duct atresia one of the main causes in the first months of life. In this, the prognosis of surgical management depends on the early diagnosis. Methods: Descriptive and prospective study, based on the analysis of a virtual survey to Medellín's healthcare workers, subgroup analysis was done according to workplace, age, sex and profession. Five images were used from the Taiwan Stool Color Card, with the authorization from their authors. Adequate recognition was considered when the participant identified the three images representing acholia / hypocholia as abnormal. Results: a response was obtained from 442 participants (53 were excluded), and only 253 (65 %) achieved adequate recognition. In the analysis by subgroups, it was found that there was a greater success in the Pablo Tobón Uribe Hospital participants with respect to other institutions (69 % and 54.6 %, respectively - p. 0.005). The participants with the lowest percentage of correct answers were general practitioners (45%). Conclusion: During the simulated assessment on the adequate identification of acholia / hypocolia, it was found that only 65% of the participating population was correct in the right identification of this clinical sign, which suggests greater attention in training for the identification of acholia / hypocolia.

Biliary Atresia Screening in India-Strategies and Challenges in Implementation.

OBJECTIVE: To assess the utilization of SCC implemented in southern India and the effect on SCC utilization of face-to-face verbal education versus video-based content delivery. METHODS: The study included newborns with postnatal age of less than 2 wk at discharge. Mothers were administered SCCs and provided standardized verbal or video health education based on the time-period of enrollment. Home based monitoring of stool color and return of SCC on postnatal day 21 was advised. Telephone surveys were conducted to identify SCC use among families that did not return the SCC by post. RESULTS: Of the 2254 newborns enrolled, 1130 were in the verbal-counseling group and 1124 in the video-counseling group. No newborns with pale stools and biliary atresia were identified. SCC return rates were 3.8% and 2.8%. Comparing the verbal and video-counseling groups, there were no differences in the conservative (81.8% vs. 81.5%) and optimistic estimates (97.1% vs. 97.3%) of SCC utilization rates. Mothers with better educational status had higher optimistic estimates of SCC utilization. CONCLUSIONS: The use of a validated SCC in Tamil with standardized information delivery leads to good utilization rates in southern India, with video content delivery being as effective as face-to-face verbal content delivery. SCC return by post is not a feasible mode of identification of card use. TRIAL REGISTRATION: The study is registered under Clinical Trials Registry - India (CTRI/2018/01/011285).

Newborn Screening for Biliary Atresia: a Review of Current Methods.

PURPOSE OF REVIEW: Biliary atresia is a serious neonatal liver disease due to obstructed bile ducts that has better outcomes when detected and treated in the first 30-45 days of life. This review examines different methods to screen newborns for biliary atresia as well as discusses observations from ongoing screening programs implemented in parts of the United States. RECENT FINDINGS: Screening strategies for biliary atresia include detecting persistent jaundice, examining stool color, testing fractionated bilirubin levels, or measuring bile acid levels from dried blood spot cards. The stool color card program is the most widely used screening strategy worldwide. An alternative approach under investigation in the United States measures fractionated bilirubin levels, which are abnormal in newborns with biliary atresia. Fractionated bilirubin screening programs require laboratories to derive reference ranges, nurseries to implement universal testing, and healthcare systems to develop infrastructure that identifies and acts upon abnormal results. Biliary atresia meets the disease-specific criteria for newborn screening. Current studies focus on developing a strategy which also meets all test-specific criteria. Such a strategy, if implemented uniformly, has the potential to accelerate treatment and reduce biliary atresia's large liver transplant burden.

Duration from the first pale stool to portoenterostomy is prognostic in biliary atresia. Comparison with age at portoenterostomy.

OBJECTIVE: Three criteria (age at first pale stool, age at portoenterostomy, and duration from the first pale stool to portoenterostomy) were assessed for prognostic value in biliary atresia. METHODS: The medical records of 116 consecutive biliary atresia patients treated by portoenterostomy after liver transplantation became available in Japan in 1989 were identified and data from 96 were analyzed retrospectively for this study. The impact of each criterion on clearance of jaundice to normal levels (total serum bilirubin ≤1.2 mg/dL) and survival with the native liver as indicators of outcome were compared according to time (≤30 days, 31-60 days, and ≥61 days). RESULTS: Age at first pale stool was ≤30 days in 53, 31-60 days in 26, ≥61 days in 17; age at portoenterostomy was ≤30 days in 7, 31-60 days in 35, ≥61 days in 54, and duration pre-portoenterostomy was ≤30 days in 50, 31-60 days in 36, ≥61 days in 10. Survival with the native liver was not significantly influenced by age at first pale stool or age at portoenterostomy, but prolonged duration (≥61 days) reduced survival with the native liver significantly (p = 0.003). Clearance of jaundice to normal levels was not affected by any criterion at any time.

A pilot study of the value of a stool color card as a diagnostic tool for extrahepatic biliary atresia at a single tertiary referral center in a low/middle income country.

BACKGROUND AND STUDY AIMS: Biliary atresia (BA) is a major cause of hepatic failure and consequent liver transplantation in pediatrics. If BA is not diagnosed early and the proper surgical intervention is not performed before the age of 3 months, the survival of the affected infant is significantly reduced. In 1994, a stool color card (SCC) for early detection of BA was developed and used in Japan, a country where the parents' socioeconomic and education levels are high. We aimed to assess the value of using the SCC as a screening tool for early diagnosis of BA at a tertiary referral center in Egypt (a low/middle-income country). PATIENTS AND METHODS: This prospective study enrolled 108 infants (56 females) aged 1 day to 4 months who presented with cholestasis to the Hepatology Unit of Cairo University Children's Hospital from January 2018 to August 2019. In most of our patients, the mothers were the main caregivers and the parents' socioeconomic and education levels were generally modest or low. We utilized the SCC courtesy of the Perinatal Services BC (Vancouver, Canada) with an Arabic translation. This SCC contains nine colored stool photos: the first six are ranked as abnormal colors and the last three are ranked as normal. RESULTS: We found that almost all referring physicians were unfamiliar with or unaware of the SCC concept. Twenty-six of our babies' mothers were illiterate and 36 had not completed their primary school education. In spite of this low education level, 43 mothers of babies who were finally confirmed to have BA correctly matched a stool color of BA on the SCC with their babies' stools, and 56 mothers of babies who were finally confirmed not to have BA correctly matched a stool color not of BA with their babies' stools. Only nine mothers made a wrong match. Therefore, the overall "lay" mothers' sensitivity and specificity in diagnosis of BA using the SCC were 93.48% (95% confidence interval [CI] 82.1%-98.63%) and 90.32% (95% CI 80.12%-96.37%), respectively. CONCLUSION: To the best of our knowledge, this is the first study reporting the use of the SCC (with an Arabic translation) in a low/middle-income country. Despite the referring physicians' unfamiliarity with the SCC and the mothers' relatively low education level at our center; SCC proved to be a simple, efficient, highly sensitive, specific, and applicable method for early diagnosis of BA. Therefore, SCC screening might increase mothers (as well as physicians) awareness of BA, and we recommend that it be more publicized and used as a mass neonatal screening tool in low/middle-income countries such as Egypt.

Screening for biliary atresia.

Early diagnosis followed by proper KP is essential for the improvement of long-term prognosis for patients with BA. It is increasingly accepted that KP at ≤ 30 days of age significantly improves native liver survival rate. Published analyses in English and Japanese indicate that screening by SCC and DB/CB is potentially feasible. Screening with SCC has been implemented in Tochigi Prefecture, Japan, since 1994. The concept of SCC was introduced from Japan to Taiwan and resulted in nationwide screening with SCC for the first time in Taiwan in 2004, followed by Japan in 2012. Home-based screening using SCC is easy and cost-effective; however, it may cause some difficulties for families in case of stools with intermediate colors. Laboratory-based screening using DB/CB may detect the suspected cases earlier, resulting in an increase in the number of patients with BA who undergo KP at ≤ 30 days of age; however, the recall rate is 1% and may be beyond an acceptable range. Further studies are needed to assess the feasibility and cost-effectiveness of both home-based (SCC) and laboratory-based (DB/CB) screening for BA.

Long-term native liver survival in infants with biliary atresia and use of a stool color card: Case-control study.

BACKGROUND: So far, there has been no epidemiological study on whether long-term native liver survival (NLS) in infants with biliary atresia (BA) is associated with use of a stool color card (SCC). METHODS: A case-control study was performed, involving two associations for patients with BA in Japan. Participants were patients with BA who were born and underwent their first open Kasai procedures (KP) between August 1994 and March 2011, and who were also members of either of two associations for patients with BA in Japan. SCC users were classified as cases and SCC non-users as controls. RESULTS: Mean age at the time of the first open KP was 59.7 and 68.2 days in SCC users and non-users, respectively (P < 0.05). According to Kaplan-Meier analysis, the probability of NLS at 12.5 years was 48.5% and 36.6% in SCC users and non-users (P < 0.05), respectively. On Cox proportional hazard modeling, not using an SCC was harmful to long-term NLS (hazard ratio, 2.61; 95% CI: 1.20-5.70; P = 0.016), adjusted for sex, age of timing of KP and type of BA. CONCLUSIONS: Long-term NLS is associated with SCC for early detection, but not associated with age or a threshold of age at KP (<90 days) in patients with BA.

Saturation of stool color in HSV color model is a promising objective parameter for screening biliary atresia.

PURPOSE: We aimed to study whether saturation in HSV color model could be a parameter for acholic stool and utilized for designing a mobile application for screening biliary atresia (BA). METHODS: Saturations of the colors in the three validated stool color cards (Taiwan, Japan, Britain) were read using PHOTOSHOP. Stools from 40 BA patients and 40 in-hospital neonates with pneumonia were photographed and analyzed with color-analyzing mobile applications. RESULTS: Saturations of normal colors in the published stool cards were all >50% (67%~99%, median 85%) and were all <50% (7~47%, median 25%) for abnormal colors. With saturation<60% as a cutoff line, acholic stools could be identified with a sensitivity of 100% and a specificity of 85%. CONCLUSION: Saturation of stool color in HSV model is a promising objective parameter for acholic stool and could be utilized in designing mobile APPs for screening BA. LEVEL OF EVIDENCE: Study of diagnostic test, level II.

Reduction of the ages at diagnosis and operation of biliary atresia in Taiwan: A 15-year population-based cohort study.

AIM: To describe the ages at diagnosis and operation of biliary atresia (BA) and its incidence over a 15-year period in Taiwan. METHODS: This was a population-based cohort study. BA cases were identified from the Taiwan National Health Insurance Research Database based on the International Classification of Diseases, Ninth Revision (ICD-9) code of BA 751.61 plus Kasai operation (ICD-9 procedure code 51.37) or liver transplantation (LT, ICD-9 procedure code 50.5). The patients' characteristics including sex, age at diagnosis, age at receiving Kasai operation and age at receiving LT were compared among three birth cohorts: (1) 1997 to 2001; (2) 2002 to 2006; and (3) 2007 to 2011. RESULTS: There were a total of 540 BA cases (275 females) with an incidence of 1.62 per 10000 live births. No seasonality of BA was noted. The mean ages at diagnosis of three cohorts were 57.9, 55.6 and 52.6 d. A linear regression model demonstrated a decreasing trend of the mean age at diagnosis (1.27 d per year). The proportion of BA cases that received the Kasai operation within 60 d of age increased from 76% to 81%. A total of 189 (35%) BA patients underwent LT. The mean age at LT was reduced from 3-year-old to 1-year-old. The rates of LT were 25.6% and 32.3% in patients who received the Kasai operation within 60 d or after 60 d of age, respectively. All patients who did not undergo a Kasai operation eventually required LT. CONCLUSION: The ages at diagnosis and operation in BA cases have decreased over time. Kasai operation performed at younger age reduces the need for LT. The incidence of BA in Taiwan fluctuates, but without certain trend.

The early screening and countermeasures of biliary atresia / 天津医药

It is generally accepted that Kasai operation is the best treatment for biliary atresia (BA). The implementation of early screen plan improves the age threshold at the suitable time point of Kasai operation. This is the key issue to improve the survival rate of autologous liver in biliary atresia. The monitoring of stool color card, B-ultrasonography and serum con?jugated bilirubin can be used for preliminary seeming biliary atresia. It is very important to improve the ability of basic unit medical staff for major improvements to the understanding of the significance of biliary atresia. In some country and district, the local government has put the screen list for BA into healthcare booklet for children. Thus, it has a significant impact of early screen plan on the diagnosis and treatment of BA, and it can improve the BA autologous liver survival time. So far, there is still no BA early screen plan in the nationwide. We should pay attention to BA, and establish early screen system in different local health unit quickly.

Latest Progress of Biliary Atresia / 实用儿科临床杂志

Biliary atresia(BA) is a common reason for obstructive jaundice in children.Pathogenesis of BA is unclear,and the prognosis is poor.Over the last 2 years,gene mutation,viral infection and autoimmune are considered to be the most possible reason for BA;Stool co-lor card has shown favourable perspective in early screening;Kasai is also the first choice for treatment of BA,which progressed in laparoscopic operation and robot surgery.Corticosteroids after surgery is still disputing.Now,liver transplantation is the only way for BA and cirrhosis.This article gave a review on the pathogenesis,diagnosis and treatment of BA.