Biliary atresia

(medicine) Failure of the bile ducts to develop in the embryo.

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Definition

Biliary atresia is the congenital failure of a fetus to develop an adequate pathway for bile to drain from the liver to the intestine.

Description

Biliary atresia is the congenital absence or closure of the ducts that drain bile from the liver. Bile is a liquid mixture of cholesterol, bile salts, and waste products, including bilirubin, which the liver excretes through thousands of tiny biliary ducts to the intestine, where the bile aids in the digestive process of dietary fats. These ducts merge into larger and larger channels, like streams flowing into rivers, until they all pour into a single duct that empties into the duodenum (first part of the small intestine). Between the liver and the duodenum this duct has a side channel connected to the gall bladder. The gall bladder stores bile and concentrates it, removing much of its water content. Then when food enters the stomach, the gall bladder contracts and empties its contents.

If bile cannot get out because the ducts are absent or blocked, it backs up into the liver (referred to as biliary stasis) and eventually into the rest of the body. The major pigment in bile is a chemical called bilirubin, which is yellow. Bilirubin is a breakdown product of hemoglobin (the red chemical in blood that carries oxygen). If the body accumulates an excess of bilirubin, it turns yellow (jaundiced). Bile also turns the stool brown; without it, stools are pale gray-, white- or fawn-colored. Bile trapped within the liver causes damage and scarring to the liver cells (cirrhosis of the liver). Scarring of the liver can cause portal hypertension (high blood pressure in the portal vein, which is the main vein carrying blood from the intestine to the liver). Portal hypertension may result in the development of fragile veins in the intestinal lining, stomach, or esophagus, which can bleed and require emergency medical attention.

Demographics

Biliary atresia is the most common lethal liver disease in children, occurring once every 10,000 to 15,000 live births. In the United States, approximately 300 cases of biliary atresia are diagnosed each year. Females are affected slightly more often than males. The incidence of biliary atresia is highest in Asian populations. The disorder also occurs in black infants at a rate approximately two times higher than that in white infants.

Causes and Symptoms

The cause of biliary atresia is unknown. However, there are indications that viral infections or autoimmune mechanisms may be responsible for the development of biliary atresia. About 10 percent of children with biliary atresia also have other associated congenital defects in blood vessels, heart, spleen, or intestines.

The affected infant appears normal at birth and during the newborn period. After about two to three weeks, the infant develops jaundice. The infant has yellow eyes and skin and dark yellow or brown urine due to build-up of bilirubin, and the stools are probably light-colored. The child's abdomen begins to swell because of a firm, enlarged liver, and the infant gets progressively more ill. Weight loss and irritability will increase as the effects of jaundice increase. Some infants may develop intense itching (pruritis), which makes them even more uncomfortable. Nearly all untreated children die of liver failure within two years.

When to Call the Doctor

The doctor should be called if an infant older than two weeks of age exhibits jaundice or has other symptoms typical of biliary atresia.

If, after surgery for biliary atresia, an infant becomes jaundiced, has a high temperature for more than 24 hours, or if there is a change in the color of the stools or urine. Also after surgery, the infant may experience an abnormal collection of fluid in the abdomen, referred to as ascites, so the doctor should be consulted if the infant's stomach is distended.

If a child has black stools, pallor, or vomiting of blood due to the development of portal hypertension, emergency medical attention is required to treat the bleeding.

Diagnosis

The persistence or development of jaundice beyond the second week in a newborn who also has light-colored stools indicates obstruction to the flow of bile. An immediate evaluation that includes blood tests and imaging of the biliary system (through ultrasound, specialized x-ray techniques, or radioactive screens of the liver) are required to confirm the diagnosis. Other liver diseases that cause symptoms similar to biliary atresia must be ruled out through the testing process. In addition, in most cases, a liver biopsy or a surgical exploration of the infant's abdomen is necessary for a definitive diagnosis.

Treatment

Surgery is the only means to treat biliary atresia. The surgeon must create an adequate pathway for bile to escape the liver into the intestine. The altered anatomy of the biliary system is different in every case, calling upon the surgeon's skill and experience to select and execute the most effective among several options. If the obstruction is only between the gall bladder and the intestine, it is possible to attach a piece of intestine directly to the gall bladder.

If the upper biliary system is also inadequate, the surgeon will attach a piece of intestine directly to the liver using the Kasai procedure, named after Morio Kasai, the Japanese surgeon who developed the procedure. The tiny bile ducts in that part of the liver where the surgery is performed discharge their bile directly into the intestine, and the channels will gradually enlarge. A possible complication after the Kasai operation is an infection in the bile ducts (cholangitis). This infection must be treated immediately with intravenous antibiotics. If the child develops ascites (abnormal build-up of fluid in the abdomen), treatment consists of medications and alteration of the diet to maintain calorie intake but to reduce salt and fluid intake.

The operation is most successful in infants under the age of eight weeks. However, in many cases, liver damage may continue to occur, and without further intervention, cirrhosis of the liver and associated complications may develop. Continued problems often develop because there are also obstructed ducts within the liver that cannot be surgically treated. In these cases, liver transplantation is required. Improved techniques of liver transplantation, which allow transplantation in children of any age, and development of drugs that help overcome the problems of organ rejection offer significant hope to children with biliary atresia who are not successfully treated with surgical techniques.

Nutritional Concerns

A low- or modified-fat diet with supplementary vitamins is often required after surgery, since the absorption of fats and vitamins can be impaired. Postoperative breastfeeding is encouraged whenever possible, as breast milk contains lipases and bile salts to aid in digestion. Infants who are formula-fed should use special formulas (Alimentum, Pregestimil) that contain chemicals to enhance digestion of dietary fats. Extra calories may also be required to help the infant gain weight. A dietary expert should be consulted to guide in the development of feeding requirements for an infant who has been treated surgically for biliary atresia.

Prognosis

Early diagnosis of biliary atresia is essential, for if left untreated, few children survive beyond the age of two years. If surgery is performed before the infant is two months old, success is much more likely, while after three months of age, the success rate is much poorer. Unfortunately for many infants, surgery is not a cure, and complications of cirrhosis of the liver may develop gradually, and the child eventually requires liver transplantation to avoid an early death. Transplantationasof2004achievesupto80to90percent one-year survival rates and promises to prevent the chronic disease that used to accompany earlier surgical procedures.

Prevention

Since the specific cause of this birth defect is unknown, there is no way known as of 2004 to prevent biliary atresia. However, it is not a hereditary condition.

Parental Concerns

Parents of children with biliary atresia require help in coping with the strain of this chronic illness as well as the stress associated with waiting for a liver transplant. Parents may also feel guilty because they feel that they may have in some way contributed to the development of biliary atresia, although as of 2004, there is no known way to prevent the disease. The American Liver Foundation organizes and coordinates mutual help groups to provide emotional support for families, to make referrals to specialists as needed, and keep parents aware of research developments.

Resources

Books

Kelly, Deirdre A., and Sheila Sherlock. Diseases of the Liver and Biliary System in Children, 2nd ed. Oxford, UK: Blackwell Publishers, 2004.

Organizations

American Liver Foundation. 75 Maiden Lane, Suite 603, New York, NY 10038. Web site: www.liverfoundation.org/.

Children's Liver Association for Support Services. 27023 McBean Parkway #126, Valencia, CA 91355. Web site: www.classkids.org/.

Web Sites

Biliary Atresia Network. Available online at (accessed December 6, 2004).

"Patient Information about Biliary Atresia." Available online at www.pediatriconcall.com/fordoctor/DiseasesandCondition/Faqs/biliaryArt.asp (accessed December 6, 2004).

[Article by: Judith Sims J. Ricker Polsdorfer, MD]

Atresia of the major bile ducts resulting in cholestasis and jaundice.

A congenital absence or underdevelopment of one or more of the biliary structures, causing jaundice and early liver damage.

Biliary atresia
Classification and external resources
Operative view of complete extrahepatic biliary atresia.
ICD-10	Q44.2
ICD-9	751.61
OMIM	210500
DiseasesDB	1400
eMedicine	ped/237
MeSH	C06.130.120.123

Biliary atresia, also known as "extrahepatic ductopenia" and "progressive obliterative cholangiopathy" is a congenital or acquired disease of the liver and one of the principal forms of chronic rejection of a transplanted liver allograft. As a birth defect in newborn infants, it has an occurrence of 1/10,000 to 1/15,000 cases in live births in the United States.^[1] In the congenital form, the common bile duct between the liver and the small intestine is blocked or absent. The acquired type most often occurs in the setting of autoimmune disease, and is one of the principal forms of chronic rejection of a transplanted liver allograft.

Infants and children with biliary atresia have progressive cholestasis with all the usual concomitant features: pruritus, malabsorption with growth retardation, fat-soluble vitamin deficiencies, hyperlipidemia, and eventually cirrhosis with portal hypertension. If unrecognized, the condition leads to liver failure -- but not kernicterus, as the liver is still able to conjugate bilirubin, and conjugated bilirubin is unable to cross the blood-brain barrier. The cause of the condition is unknown. The only effective treatments are certain surgeries such as the kasai procedure, or liver transplantation.

Contents 1 Symptoms and diagnosis 2 Pathophysiology 3 Treatment 4 References 5 External links

Symptoms and diagnosis

Initially, the symptoms are indistinguishable from neonatal jaundice, a common phenomenon. Symptoms are usually evident between one and six weeks after birth. Besides jaundice, other symptoms include clay colored stools, dark urine, swollen abdominal region and large hardened liver (which may or may not be observable by the naked eye). Prolonged jaundice that is resistant to photo therapy and/or exchange transfusions should prompt a search for secondary causes. By this time, liver enzymes are generally measured, and these tend to be grossly deranged, hyperbilirubinaemia is conjugated and therefore does not lead to kernicterus. Ultrasound investigation or other forms of imaging can confirm the diagnosis. Further testing includes radioactive scans of the liver and a liver biopsy.

Biliary atresia seems to affect girls slightly more often than boys. Within the same family, it is common for only one child in a pair of twins or only one child within the same family to have it. Asians and African-Americans are affected more frequently than Caucasians. There does not appear to be any link to medications or immunizations given immediately before or during pregnancy.

Pathophysiology

There is no known cause of biliary atresia. There have been many theories about ethiopathogenesis such as Reovirus 3 infection, congenital malformation, congenital CMV infection, autoimmune theory. This means that the etiology and pathogenesis of biliary atresia are largely unknown. However, there have been extensive studies about the pathogenesis and proper management of progressive liver fibrosis, which is arguably one of the most important aspects of biliary atresia patients. As the biliary tract cannot transport bile to the intestine, bile is retained in the liver (known as stasis) and results in cirrhosis of the liver. Proliferation of the small bile ductules occur, and peribiliary fibroblasts become activated. These "reactive" biliary epithelial cells in cholestasis, unlike normal condition, produce and secrete various cytokines such as CCL-2 or MCP-1, Tumor necrosis factor (TNF), Interleukin-6 (IL-6), TGF-beta, Endothelin (ET), and nitric oxide (NO). Among these, TGF-beta is the most important profibrogenic cytokine that can be seen in liver fibrosis in chronic cholestasis. During the chronic activation of biliary epithelium and progressive fibrosis, afflicted patients eventually show signs and symptoms of portal hypertension (esophagogastric varix bleeding, hypersplenism, hepatorenal syndrome(HRS), hepatopulmonary syndrome(HPS)). The latter two syndromes are essentially caused by systemic mediators that maintain the body within the hyperdynamic states. There are three main types of extrahepatic biliary atresia:- Type I: atresia restricted to the common bile duct. Type II: atresia of the common hepatic duct. Type III: atresia of the right and left hepatic duct. Associated anomalies include, in about 20% cases, cardiac lesions, polysplenia, situs inversus, absent vena cava and a preduodenal portal vein.

Treatment

If the intrahepatic biliary tree is unaffected, surgical reconstruction of the extrahepatic biliary tract is possible. This surgery is called a Kasai procedure (after the Japanese surgeon who developed the surgery, Dr. Morio Kasai) or hepatoportoenterostomy. This procedure is not usually curative, but ideally does buy time until the child can achieve growth and undergo liver transplantation.

If the atresia is complete, liver transplantation is the only option. Timely Kasai portoenterostomy (e.g. < 60 postnatal days) has shown better outcomes. Nevertheless, a considerable number of the patients, even if Kasai portoenterostomy has been successful, eventually undergo liver transplantation within a couple of years after Kasai portoenterostomy.

Recent large volume studies from Davenport et al. (Ann Surg, 2008) show that age of the patient is not an absolute clinical factor affecting the prognosis. In the latter study, influence of age differs according to the disease etiology—i.e., whether isolated BA, BASM (BA with splenic malformation ), or CBA(cystic biliary atresia).

It is widely accepted that corticosteroid treatment after a Kasai operation, with or without choleretics and antibiotics, has a beneficial effect on the postoperative bile flow and can clear the jaundice; but the dosing and duration of the ideal steroid protocol have been controversial ("blast dose" vs. "high dose" vs. "low dose"). Furthermore, it has been observed in many retrospective longitudinal studies that steroid does not prolong survival of the native liver or transplant-free survival. Davenport at al. also showed (hepatology 2007) that short-term low-dose steroid therapy following a Kasai operation has no effect on the mid- and long-term prognosis of biliary atresia patients.

References

1. ^ Sleisenger, MH; Feldman M, Friedman, LS (2006). Sleisenger and Fordtran's gastrointestinal and liver diease: pathophysiology, diagnosis, management (8th Edition ed.). Philadelphia: Saunders. 

External links

• Information from the European Biliary Atresia Registry
• Biliary Atresia Research Consortium (U.S.)
• Children's Liver Disease Foundation (U.K.)
• Choledochal cyst associated with extrahepatic bile duct atresia
• How Inflammation Causes Biliary Atresia by Jorge Bezerra, MD at Cincinnati Children's Hospital Medical Center

v d e Congenital malformations and deformations of digestive system (Q35–Q45, 749–751) Upper GI tract Tongue, mouth and pharynx Cleft lip and palate · Van der Woude syndrome · tongue (Ankyloglossia, Macroglossia, Hypoglossia) Esophagus EA/TEF (Esophageal atresia: types A, B, C, and D, Tracheoesophageal fistula: types B, C, D and E) esophageal rings (Esophageal web  · upper, Schatzki ring · lower) Stomach Pyloric stenosis · Hiatus hernia Lower GI tract Intestines Intestinal atresia (Duodenal atresia) · Meckel's diverticulum · Hirschsprung's disease · Intestinal malrotation · Dolichocolon · Enteric duplication cyst Rectum/anal canal Imperforate anus · Persistent cloaca Accessory Pancreas Annular pancreas · Accessory pancreas · Johanson–Blizzard syndrome Pancreas divisum Bile duct Choledochal cysts (Caroli disease) · Biliary atresia Liver Alagille syndrome · Polycystic liver disease M: MOU anat/devp noco/cofa(c)/cogi/tumr, sysi proc (peri), drug (A1) M: DIG anat(t, g, p)/phys/devp/enzy noco/cong/tumr, sysi/epon proc, drug(A2A/2B/3/4/5/6/7/14/16), blte

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