1. OVERVIEW OF DISORDERS OF THE BILIARY TRACT IN CHILDREN
Aswad H. Al.Obeidy
FICMS, FICMS GE&Hep
Kirkuk General Hospital

2. OVERVIEW OF DISORDERS OF THE BILIARY TRACT IN CHILDREN
Cholestatic liver disease results from processes that interfere with either bile formation by hepatocytes or bile flow through the intrahepatic and extrahepatic biliary trees
A number of these disorders result from defective ontogenesis as well as from a failure of postnatal adaptation to the extrauterine environment
The general features of the many cholestatic liver diseases in the neonate are similar, and a central problem of pediatric hepatology is differentiating intrahepatic from extrahepatic cholestasis

3. OVERVIEW OF DISORDERS OF THE BILIARY TRACT IN CHILDREN
The treatment of metabolic or infective liver diseases and the surgical management of biliary anomalies require early diagnosis
Even when effective treatment is not possible, infants and children with progressive liver disease benefit from optimal nutritional support and medical management of chronic liver disease before they are referred for hepatic transplantation

4. Disorders of the Biliary Tract in Infants and Children
Cholangiopathies Extrahepatic biliary atresia
Choledochal cysts
Spontaneous perforation of the common bile duct
Mucous plug syndrome
Sclerosing cholangitis (neonatal, inflammatory bowel disease–associated, immunodeficiency)
Paucity of intrahepatic bile ducts (syndromic and nonsyndromic)
Caroli's disease
Cystic fibrosis
Biliary helminthiasis
Idiopathic bile duct stricture (possibly congenital)
Post-traumatic common duct stricture
Bile duct tumors (intrinsic and extrinsic)
Bile duct obstruction due to pancreatic disease (inflammatory or neoplastic)
Graft-versus-host disease
Allograft rejection
Disorders of the gallbladderAnomalies
Cholelithiasis
Acute cholecystitis
Chronic cholecystitis
Acalculous cholecystitis
Acute hydrops of the gallbladderTumors

5. Relative Frequencies of Various Forms of Neonatal Cholestasis
Disorder Cumula. Percentage
Idiopathic neonatal hepatitis
Extrahepatic biliary atresia
Alpha1-antitrypsin deficiency
Intrahepatic cholestatic syndromes (Alagille syndrome, Byler's disease, others)
Choledochal cyst
Bacterial sepsis
Hepatitis (cytomegalovirus, rubella, herpes, others)
3-5
Endocrinopathy (hypothyroidism, panhypopituitarism)≈1
Galactosemia ≈1
Inborn errors of bile acid metabolism ≈1O
Other metabolic disorders ≈1

6. OVERVIEW OF DISORDERS OF THE BILIARY TRACT IN CHILDREN
Because of the immaturity of hepatobiliary function, the number of distinct disorders that exhibit cholestatic jaundice may be greater during the neonatal period than at any other time of life
Liver dysfunction in the infant, regardless of the cause, is commonly associated with bile secretory failure and cholestatic jaundice
Although cholestasis may be traced to the level of the hepatocyte or the biliary apparatus, in practice there may be considerable overlap among disorders with regard to the initial and subsequent sites of injury
Furthermore, another common histologic variable that often accompanies neonatal cholestasis is bile ductular paucity, or a diminution in the number of interlobular bile ducts
Serial liver biopsy specimens usually show a progressive drop in the number of bile ductules per portal tract, with a varying amount of associated inflammation

7. DIAGNOSIS OF BILIARY TRACT DISEASE IN INFANTS AND CHILDREN
In most infants with cholestatic liver disease, the condition appears during the first few weeks of life
Differentiating conjugated hyperbilirubinemia from the common unconjugated, physiologic hyperbilirubinemia of the neonate or the prolonged jaundice occasionally associated with breast-feeding is essential
The possibility of liver or biliary tract disease must be considered in any jaundiced neonate older than 14 days
The stools of a patient with well-established biliary atresia are acholic; however, early in the course of incomplete or evolving biliary obstruction, the stools may appear normally or only intermittently pigmented
Life-threatening but treatable disorders such as bacterial infection and a number of inborn errors of metabolism must be excluded
Furthermore, the success of surgical procedures in relieving the biliary obstruction of biliary atresia or a choledochal cyst depends on early diagnosis and surgery

8. Evaluation of the Infant with Cholestasis
History and physical examinationInclude
Details of family history
Pregnancy
Presence of extrahepatic anomalies
Stool color

9. Tests to establish the presence and severity of liver disease
Fractionated serum bilirubin analysis
Liver biochemical tests (AST, ALT, alkaline phosphatase, 5′ nucleotidase, gamma glutamyl transpeptidase)
Tests of liver function (prothrombin time, partial thromboplastin time, coagulation factors, serum albumin level, serum ammonia level, serum cholesterol level, blood glucose)

10. Tests for infection Complete blood count
Bacterial and viral cultures of blood, urine, and other sites if indicated
Paracentesis if ascites is present
Serologic tests (for hepatitis B, TORCH agents, syphilis, EBV, others)

11. Metabolic studies Urine for reducing substances
Alpha1-antitrypsin level and phenotype
Sweat chloride analysis
Metabolic screen (urine and serum amino acids, urine organic acids)
Thyroid hormone, thyroid-stimulating hormone (evaluation of hypopituitarism as indicated)
Serum iron and ferritin
Urine and serum analyses of bile acids and bile acid precursors
Red blood cell galactose-1-phosphate uridyl transferase activity

12. Imaging studies Ultrasonography of the liver and biliary tract
Hepatobiliary scintigraphy
Radiography of the long bones and skull for congenital infection and of the chest for lung and cardiac disease
Magnetic resonance cholangiography
Percutaneous or endoscopic cholangiography (rarely indicated)

13. Procedures Duodenal intubation to assess fluid for bile pigment
Percutaneous liver biopsy (for light and electron microscopic examination, enzymologic evaluation)
Bone marrow examination and skin fibroblast culture for suspected storage disease
Exploratory laparotomy and intraoperative cholangiography

14. Ultrasonography
Can be used to assess the size and echogenicity of the liver
Even in neonates, high-frequency, real-time ultrasonography can usually define the presence and size of the gallbladder, detect stones and sludge in the bile ducts and gallbladder, and demonstrate cystic or obstructive dilatation of the biliary system
Extrahepatic anomalies also may be identified
A triangular cord or band-like periportal echogenicity (3 mm or greater in thickness), which represents a cone-shaped fibrotic mass cranial to the portal vein, appears to be a specific ultrasonographic finding in the early diagnosis of biliary atresia
The gallbladder “ghost” triad, defined as gallbladder length of less than 1.9 cm, lack of a smooth (complete) echogenic mucosal lining, and an indistinct wall and irregular or lobular contour, has also been proposed as a criterion for biliary atresia

15. Magnetic resonance cholangiography
Performed with T2-weighted turbo spin-echo sequences, is widely used to assess the biliary tract in all age groups
In a 1999 study, MRC reliably demonstrated the common bile duct and gallbladder in normal neonates
In some patients with biliary atresia, nonvisualization of the common bile duct and demonstration of a small gallbladder have been characteristic MRC findings
A subsequent study found that MRC is 82% accurate, 90% sensitive, and 77% specific for depicting extrahepatic biliary atresia
Contrary to previous reports, falsepositive and false-negative findings occur with MRC
Differentiating severe intrahepatic cholestasis from biliary atresia may be difficult because delineation of the extrahepatic biliary tree by MRC depends on bile flow

16. Percutaneous transhepatic cholangiography
May be of value in visualizing the biliary tract in select patients
However, the technique is more difficult to perform in infants than in adults, because the intrahepatic bile ducts are small and most disorders that occur in infants do not result in dilatation of the biliary tree
Endoscopic retrograde cholangiopancreatography (ERCP) may be useful in evaluating children with extrahepatic biliary obstruction and has been performed successfully in a small number of cholestatic neonates
Considerable technical exper-tise is required of the endoscopist to complete this procedure in infants
General anesthesia is needed in most neonates for a satisfactory examination

17. Percutaneous liver biopsy
Is particularly valuable in evaluating cholestatic patients and can be performed in even the smallest infants with only sedation and local anesthesia
A diagnosis of extrahepatic biliary atresia can be made on the basis of clinical and histologic criteria in 90% to 95% of patients
When doubt about the diagnosis persists, the patency of the biliary tree can be evaluated directly by a minilaparotomy and operative cholangiogram