Early detection of biliary atresia in primary health care: still a problem

Introduction

Biliary atresia (BA) is the most common cause of pediatric end-stage liver disease and is the leading cause of liver transplantation in children. It remains a challenge for clinicians.¹ BA is found worldwide, with incidence rates of 1 in 10-19,000 in Europe and North America, and higher incidence rates of 1 in every 3,000 infants in East Asia.^2–4

Biliary atresia is manifested with abnormal narrowing of the bile ducts, blockage of the bile ducts to the absence of bile ducts in the liver.² Early detection of biliary atresia is crucial for diagnosis and the rate of disease progression. Currently, increasing evidence has shown that the development of BA is associated with infections, such as perinatal viral infections. The presence of infection can trigger neonatal cholestasis which begins with progressive inflammation of the intrahepatic and extrahepatic bile ducts.² Biliary obstruction can happen within the first few weeks after birth.¹ The best prognosis of BA remains dependent on early diagnosis and surgical treatment.⁵

There are two clinical forms of BA, perinatal and congenital. In the perinatal form of BA, the infant has no congenital abnormalities and the onset of jaundice begins during or after the second week of life. This contrasts to the congenital form, in which signs of cholestasis appear soon after birth and associated with non-hepatic congenital anomalies.⁵ Most cases (80%) are considered perinatal form.³

Clinically, in infants with biliary atresia, cholestatic jaundice develops in the first few weeks of life followed by acholic stools, dark urine, hepatomegaly, poor growth, progressing to cirrhosis, portal hypertension, and liver failure.^2,5 The symptoms of BA continue to worsen two weeks after birth. It is different with physiological jaundice. Physiological jaundice will improve within two weeks and get better. Meanwhile, in cholestasis that occurs due to biliary atresia, jaundice will worsen.³ Unfortunately, identification of infants with cholestatic jaundice is quite difficult because it appears similar to the physiological jaundice that is very common in early infancy.¹ Currently, the Stool Color Card has been introduced as an early detection tool for biliary atresia in infants which can diagnose earlier, shorten surgical treatment time, and improve the long-term prognosis of children with biliary atresia.⁵

Unfortunately, early diagnosis of biliary atresia is still challenging. The delay in diagnosing BA is the main problem, especially in Indonesia. The lack of knowledge and awareness about early detection of BA among primary healthcare providers is the important cause of delayed diagnosis of BA.⁶ This study aims to analyses the knowledge about BA and evaluate the effectiveness of health education to increase knowledge of primary health care providers in early detection of BA in infants. Increasing primary health care awareness by conducting an educational seminar on early detection of BA was expected in this study.

Methods

Results

In this study, there were 252 participants involved and the majority (92.9%) were female. The mean age of the participants was 40.7 ± 9.4 years old (Min-Max: 22-71 years old). Most of the participants were midwives (61.9%) with a diploma graduate (82.5%). A total of 77.8% of participants have years of service in primary health care > 5 years as described in Table 1.

Discussion

Biliary atresia is present with findings: (1) the occurrence of total extrahepatic bile duct obstruction (2) the presence of proliferation of the intrahepatic bile ducts, and (3) the discovery of intrahepatic fibrosis that occurs at an early age.⁷ BA is found worldwide, and incidence rate is 1 in 10-19,000 infant in Europe and North America, up to 6.5 to 7.5 in 100 000 infant in the US mainland until high incidence rate to 1 in 3,000 infants in East Asia.^1–4 But no official data on the incidence of BA has been published in Indonesia.⁸

Although BA is a rare disease, BA is the leading cause of liver transplantation in children and the most common cause of death from liver disease in infants.⁹ The prognosis of BA in infants is influenced by several factors, including age at the time of surgical intervention and the anatomy of the bile duct remnant. Nearly half of all infant with BA survive into adolescence if Kasai surgery is carried out early.¹⁰

Unfortunately, the challenge remains in recognizing that infants with jaundice may have BA, not a common physiologic jaundice. Delayed diagnosis is still a problem worldwide.¹¹ Delayed diagnosis and Kasai procedure performed after three months of age have a significantly poor prognosis for survival of the original liver.¹² Kasai surgery can improve long-term liver survival and reduce the need for a liver transplant if performed before 60 days of age.^13,14 Liver cirrhosis is major morbidity resulting from untreated BA, requires very costly liver transplantation that Indonesia has limited facilities. Not all centers in Indonesia can perform liver transplants. Therefore, the most likely thing to do is to carry out the Kasai procedure as early as possible.¹⁵

An early diagnosis of biliary atresia is difficult. Delay in diagnosing BA is also a major source of problems in therapy, especially in Indonesia. Global efforts are urgently needed to increase the rate of BA diagnosis as early as possible.¹⁵ The lack of knowledge and awareness about early detection of BA among primary healthcare providers is the important cause of delayed diagnosis of BA.⁶

In this study, there were 40.5% of the primary health care provider stated that newborns < 28 days old may have normal (physiological) jaundice, which is characterized by icteric sclera, pale stools, and dark urine. Infants suffering from BA generally appear as healthy as any other infant when they are neonates.^1,2 Clinically, in the early condition of BA, infants with BA are indistinguishable from infants with non-conjugated hyperbilirubinemia, such as physiologic jaundice and breast milk-associated jaundice. Then, making the diagnosis of infant jaundice other than physiologic or breast milk-related jaundice is still a challenge today.¹ However, in BA jaundice will extend beyond two weeks of age and infants will experience other complaints, such as pale stools, dark urine, poor growth, increased abdominal circumference due to ascites and splenomegaly, and other complications due to liver damage.^2,9

Overall, there were 27.4% health care provider showed that all jaundice that occurs in newborn will always improve on their own in this study. A total of 24.2% primary health care provider stated that newborn with prolonged jaundice does not need further examination, it is enough to just expose to the sun. The evaluation of bilirubin serum should be done in infant with prolonged jaundice. Then the presence of BA should be considered for any jaundiced infant with acholic stools and accompanied by an increase in the serum conjugated bilirubin concentration.¹

There was no difference in pre- and post- test scores for questions about complication of biliary atresia in this study and the need for liver transplantation. The primary health care provider understands about biliary atresia and its complications, however, in this study it was found that only 69.0% of participants understood that jaundice due to biliary atresia must be detected as early as possible and surgery performed before the age of two months.

Early diagnosis and treatment are necessary in infants with BA.¹ There was a significant difference between the pretest and posttest scores (p value 0.000). The post test score (median 17) was higher than the pretest score (median 15) after interventional health education. Improving knowledge to early detection of biliary atresia using screening with stool color cards is a promising and economically feasible strategy.^11,16 It is necessary to increase the awareness of primary healthcare providers to early detection of BA for improving the outcomes of the Kasai procedure and reduce the need for liver transplantation.¹⁰ Therefore, it is very important to socialize how to early detection BA in Indonesia, especially in the regions to reduce the delay rate in the referral of infants with BA using interventional health education.

Serum conjugated bilirubin concentrations and stool color cards are the two BA screening methods currently in use.¹ A study in the United Kingdom stated that baby with conjugated bilirubin more than 20% of total bilirubin was followed up in a community setting, from this study several liver diseases such as neonatal hepatitis, extra-hepatic biliary atresia, Alagille syndrome, hypopituitarism, and alpha-1-antitrypsin deficiency were detected.¹⁷ Another study showed that at 24 to 48 hours of life, subjects with BA had mean conjugated bilirubin levels significantly higher than those of controls, and it can happen shortly after birth.¹⁸ Thus, serum conjugated bilirubin levels can be a valuable screening test for BA.¹

Screening with stool color cards is currently an important strategy because it requires lower costs and better results.¹⁶ Stool Color Cards have been used in China, Taiwan, and Japan to shorten the age at diagnosis and shorten the time between diagnosis and the Kasai procedure.^19,20 A 19-year cohort study in Japan showed that the sensitivity and specificity of stool color card screening at one-month evaluation were 76.5% and 99.9%, respectively.²¹ In Taiwan, the stool color card screening had a sensitivity and specificity of 89.7% and 99.9%, respectively.²² However, in this study, it was found that 78.2% of health workers in primary health facilities understood the stool color card used as a screening tool for biliary atresia in infants. The optimization of biliary atresia screening is still needed using the health intervention to primary health care provider to reduce the need for liver transplantations.¹³

This study was the first research conducted and provides new information that one of the failures of early detection of biliary atresia is the uneven level of knowledge about jaundice and biliary atresia in primary health facilities which is the main milestone in public health services. The results of this study can be used as the basis for policies to carry out more massive socialization to health workers in primary health facilities about biliary atresia. The weakness of this study is the limited number of subjects. Further research with a larger number of subjects and a wider area is needed to determine the level of knowledge of early detection of biliary atresia in Indonesia.

Conclusion

The natural history of biliary atresia has been described. Early diagnosis provides a better prognosis for infants with biliary atresia. These findings suggest that improving knowledge to early detection of biliary atresia is needed to primary healthcare providers, including information about prolonged jaundice and screening with the stool color card for improving outcomes in BA in Indonesia. Health education interventions has significantly increased the knowledge of primary healthcare providers about early detection of BA. Further studies with larger subjects and area are needed to evaluate the effectiveness and feasibility of potential education for early identification of infants with biliary atresia in Indonesia.