Biliary Atresia Flashcards
Which one of the following statements concerning biliary atresia is true?
A. Without treatment, the average survival is 5 years.
B. The hallmark pathologic findings are giant cell transformation and hepatocellular necrosis.
C. There is a higher incidence in Europe and North America.
D. Ultrasound of the liver and gallbladder is an integral part of the diagnostic workup.
E. Biliary atresia is the third most common indication for pediatric liver transplantation.
ANSWER: D
COMMENTS: Biliary atresia is characterized by progressive, irreversible fibrosis of the extrahepatic and intrahepatic bile ducts.
There is no proved effective medical therapy. If surgical correction is not performed, the obliterative process progresses.
Biliary cirrhosis and portal hypertension develop, followed by death by 2 years of age.
Severe cholestasis, bile duct proliferation, and inflammatory cell infiltration are pathologic findings in biliary atresia.
Hepatocellular necrosis and giant cell transformation are seen with neonatal hepatitis.
Biliary atresia is the number one indication for pediatric liver transplantation.
Biliary atresia should be suspected in an infant with persistent neonatal jaundice and elevated conjugated bilirubin.
It occurs in 1/10,000 live births and is most prevalent in Asia.
The workup for suspected biliary atresia includes ultrasound imaging of the liver and gallbladder, hepatobiliary iminodiacetic acid (HIDA) scanning, and percutaneous liver biopsy.
Typically, the extrahepatic bile ducts cannot be seen on ultrasound imaging, and the gallbladder is diminutive or absent.
However, even with these tests, the final diagnosis often is made at surgical exploration.
An intraoperative cholangiogram will demonstrate a lack of opacification of the intrahepatic biliary tree.
When identified, a Kasai procedure is indicated. The goals of the Kasai procedure are to restore biliary flow by performing a Roux-en-Y portojejunostomy after the resection of the gallbladder, extrahepatic bile ducts, and the fibrotic portal plate.
With regard to the Kasai procedure for the treatment of biliary atresia, which of the following statements is true?
A. It is most successfully performed after 3 months of age.
B. Cholangitis rarely complicates a successful procedure.
C. Portal hypertension remains problematic despite a successful operation.
D. If hepatic transplantation is needed, an initial Kasai enterostomy is not indicated.
E. Cholangitis is an infrequent late complication.
ANSWER: C
COMMENTS: Biliary atresia occurs as a part of a spectrum of anomalies of infantile obstructive cholangiopathy.
Variable patterns of ductal involvement of the intrahepatic and extrahepatic biliary tree are seen, with 10% of patients initially having an extrahepatic disease only.
The goals of treatment are to establish biliary flow and prevent the late complications of biliary cirrhosis and hepatic failure.
Hepatoportoenterostomy, the Kasai procedure, is most successful in establishing biliary drainage when performed during the patient’s first 2 months of life.
The success rate falls dramatically after 3 months of age.
Cholangitis, biliary cirrhosis, hepatic failure, and portal hypertension remain late problems despite the fact that bile drainage is achieved.
Attempts to reduce later cholangitic complications include prolonged use of antibiotics and steroids to minimize inflammation and infection.
One- third of patients undergoing a Kasai procedure for biliary atresia will have a successful biliary drainage and require no further intervention.
One-third will initially have adequate drainage but will eventually progress to hepatic fibrosis and require transplantation.
The final third will never have adequate drainage and will require liver transplantation to survive.
Hepatic transplantation has been successful in the treatment of this problem but has not replaced biliary-enteric anastomosis as the initial procedure.
An unsuccessful hepatoportoenterostomy does not preclude later hepatic transplantation and is therefore the initial surgical management of biliary atresia.
Discuss biliary atresia.
Biliary Atresia (BA) is the most common surgical cause of conjugated jaundice in infancy, and consists of a progressive inflammatory destruction and obliteration of variable lengths of the biliary tract.
If left untreated it leads to liver failure and death within few months.
It is best treated by an attempt at restora- tion of bile flow from the native liver by excision of the extrahepatic bile ducts and reconstruction using a jejunal Roux loop (Kasai portoenterostomy).
With this clearance of jaundice of 50–60% can be achieved in large centres with appropriate adjuvant therapy.
Failure to clear jaundice or onset of complications such as recurrent cholangitis, ascites and recurrent bleeding from variceal formation are indications for liver transplantation.
What is biliary atresia?
Biliary atresia (BA) is unique to the neonatal period and first described by the Scottish paediatrician John Thomson in 1892.
It is the most common surgical cause of conjugated jaundice in infancy, and consists of a progressive inflammatory destruction and obliteration of variable lengths of the biliary tract.
If left untreated it leads to liver failure and death within few months.
A comprehensive aetiology for BA has not been exhaustively formulated yet.
Nevertheless, it is clear that the pathogenesis of the disease includes both a mechanical obliteration and in some a destructive inflammatory process of the bile ducts.
What is the incidence of BA?
It varies across the globe with relatively high incidence in Taiwan, mainland China and Japan of 1 in 5–10,000 live births to 1 in 15–20,000 in North America and Europe.
What classifications are in use for BA?
Phenotypic classification
This classification is based on objective features and represents a useful tool for the clinical assessment and management of the patients. It is possible to recognise four main groups.
- Syndromic BA (10% of European and North America, much rarer in China)
a. BA splenic malformation (BASM) syndrome—Association of BA, splenic anomalies (i.e. polysplenia or asplenia), vascular anomalies (e.g. preduodenal portal vein and absence of vena cava), situs inversus and cardiac anomalies. Related to maternal diabetes. Some have PKD1L1 mutations.
b. Cat eye syndrome—BA and coloboma (defect of iris), anorectal malformations and cardiac anomalies. Due to chromosome 22 aneuploidy.
c. Other more common congenital anomalies such as esophageal atresia, jejunal atresia and cardiac malformations can be associated with BA without a defined syndromic picture.
- Cystic BA (5–10%)
Characterized by an extrahepatic cyst formation in an otherwise obliterated biliary tract. Larger examples can be detected antenatally with ultrasonography.
This type may be easily confused with an obstructed choledochal malformation, the differential is intraoperative and demonstrable on cholangiography. If mucus is obtained puncturing the cyst, that is a confirmation of BA. Cholangiogram may show dilating intrahepatic ducts characteristic of a choledochal malformation.
- Cytomegalovirus associated BA (10–20%—marked worldwide variation)
This is defined by serology (IgM+ve). These infants are often associated with a later presentation and more deranged biochemical markers and a greater degrees of liver inflammation and fibrosis.
Effectiveness of Kasai portoenterostomy (KPE) and overall survival are also poor in these patients. This has been negated by specific adjuvant anti-viral therapy (e.g. ganciclovir) in some studies.
- Isolated BA
This is the largest group of patients, with heterogeneous features in terms of response to surgical management and prognosis.
Anatomical Classification
The most common anatomical classification, based on the Japanese Association of Pediatric Surgeons, divides BA in 3 categories based on the level of biliary obstruction (Fig. 36.1).
• Type 1: obstruction at the level of CBD (5–10%), often associated with cyst.
- Type 2: at the level of the CHD (rare)
- Type 3: at level of porta hepatis.
How do children with BA present?
The invariable triad of symptoms in infants with BA consists of jaundice, dark urine and pale, acholic stool.
These signs are usually present from birth, while hepatosplenomegaly and ascites secondary to portal hypertension are usually later developments.
Some may also have a coagulopathy secondary to vitamin K malabsorption and present with bleeding.
How do you diagnose BA in infants with jaundice?
The key biochemical differentiation is to determine whether there is an elevated conjugated (aka direct) bilirubin.
All surgical causes have this.
Most medical causes including “physiological jaundice” are predominantly unconjugated.
The differential diagnoses of “surgical jaundice” are: BA, choledocal malformations, inspissated bile syndrome and spontaneous perforation of the bile duct.
Ultrasonography should enable a more precise diagnosis showing intrahepatic duct dilation in all of these except for BA.
An algorithm is suggested to lead to definitive pre-laparotomy diagnosis of BA.
Although percutaneous liver biopsy is widespread, others simply opt for on-table laparoscopy or cholangiography.
ERCP is certainly possible in infancy albeit uncommonly performed.
What is the current treatment for BA?
Most infants with BA should have an attempt at restoring bile flow and abbreviating the liver damage.
The standard operation is termed Kasai portoenterostomy (KPE), but actually details of technique vary from surgeon to surgeon.
Age at KPE is important and delay is detrimental, but formerly held cut-offs values were simply naïve.
Nevertheless, beyond 100 days of age outcome suffers.
Late-presenting infants in this category may be considered for primary liver transplant certainly if cirrhotic features are obvious.
What is a Kasai portoenterostomy?
This was developed in the 1950s and 60 s in Japan by Morio Kasai and consists of excision of all apparently solid proximal bile duct remnants and Roux loop reconstruction to the denuded porta hepatis.
The length of the Roux limb is typically 40 cm.
Variations in the form of the creation of stomas in the loop are no longer done.
Frozen section of the resected part is also redundant as the principle idea of a radical resection is to excise every visible part of the biliary tract, leaving nothing behind.
Beyond using the laparoscope for diagnosis, it is possible to perform a laparoscopic approximation of a KPE [3].
Nonetheless, the only large series have been from China and Japan and caution is advised.
There is certainly no advantage, unless it is to the transplant surgeon later on!
Technical tips
• An on-table diagnosis should be clear as mostly the gallbladder is either full of clear mucus or so atrophic that a lumen can’t be found to do a cholangiogram. Bile in an intact gallbladder implies it is not BA or if it is, it is Type 1 and then a cyst should be visible.
• In case of situs inversus the operator should be on the left side.
• In case of malrotation, extra-care has to be placed in forming the Roux loop to avoid mesenteric defects which might predispose to an internal hernia. Obviously, it can no longer be retrocolic, if a Ladd’s procedure is also contemplated.
• The presence of portal hypertension can be challenging. Bipolar diathermy is the main hemostatic tool; however, this should not be applied to the transected portal plate in order to avoid bile ductule damage. Pressure or hemostatic material should suffice. Furthermore, full-thickness sutures or staples may be recommended for the jejuno-jejunal anastomosis.
How are infants managed in the post-operative period?
Prophylactic post-operative intravenous antibiotics should reflect the local microbiological policy.
Some centers continue oral antibiotics for months after though the evidence in prevention of cholangitis is weak.
The use of more specific therapy is controversial [4].
High-dose steroids (≈4–5mg/kg/day prednisolone) are widely prescribed, certainly outside of North America.
The START randomized placebo controlled trial was equivocal, but underpowered to show a “significant” difference (though there was one of 15%) [5].
Ursodeoxycholic acid is less controversial, but has no evidence base.
Anti-viral adjuvant therapy should be considered for those infants who are CMV IgM+ve.
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Postop Care:
1) Prevent inflammation within 4 weeks (monitor stool color).
2) Give/revise antibiotic to enable bilioenteric fistula.
3) Medium chain triglyceride formula milk advocated, maximize caloric input and facilitate liver absorption.
4) Steroids can be given.
Complications
1) Cholangitis withn first 2 years (bil>2.5mg/dl, acholic stools, leukocytosis, fever 38.5).
Tx: Give TMP-SMX.
2) Portal HTN
3) Splenomegaly, esophageal varices, ascites due to persistent hepatic fibrosis. Tx: Non surgical as long as hepatic function is preserved, consider liver transplant if not.
4) Hepatopulmonary syndrome
Dx: Cyanosis, dyspnea from vasoactive compounds from mesenteric circulation. Workup: ABG at room air compared to ABG at O2 supplement.
Tx: Liver transplant.
Prognosis
70% 10yr survival if KPE done withn 60days.
Better prognosis if bile ductules >150um diameter.
Poor prognosis if with associated CHD, hypersplenism, immunocompromised.
Indications for Liver transplant:
Lack of bile drain
Developmental retardation
Socially unacceptable complications.
87% 10 yr survival for living donor for liver transplant.
What complication can occur after KPE?
KPE may be completely futile and not change the level of jaundice or pigment in their stool.
Primary non-responders will need transplant consideration before 1–2years of age.
Other more specific complications may occur after KPE, including:
Cholangitis
Ascending bacterial cholangitis is described in up to 50% of the patients, usually within 2 years after KPE, then the risk diminishes. Gram negative bacteria are usually responsible and should be the target for appropriate antibiotics (e.g. meropenem, gentamicin, piperacillin-tazobactam). Clinically it presents with worsening jaundice, fever, rising inflammatory markers and altered biochemical liver function.
Portal Hypertension
Portal venous pressure is raised in >70% of infants at the time of KPE. Nevertheless, initial values correlate poorly with outcome, even development of varices. This implies that the formation of varices depends on the evolution of the fibrotic liver process following KPE rather than the condition of the liver at the time of the surgery. Endoscopic surveillance suggests endoscopically evident varices are present in 60% of patients, of which maybe half will bleed.
Acute bleeding should be treated medically at first with vasopressin or somatostatin analogues. In severe bleeding, a Sengstaken tube may have to be inserted as an emergency procedure. Endoscopic management includes banding in older children and adults while sclerotherapy is still the treatment of choice in infants.
Patients where gastrointestinal bleeding is associated with worsening liver function need evaluation for transplant.
Ascites
Ascites is often a consequence of portal hypertension but other features related to liver failure maybe involved (i.e. hypoalbuminemia and hyponatremia). Low salt diet and fluid balance management, including diuretics, are the first-line treatment. Persistent ascites may simply reflect end-stage liver failure and consideration of transplant.
Inguinal hernias
There is a higher incidence of these than the normal population possibly caused by ascites and increased abdominal pressure.
What factors affect outcome for biliary atresia?
- The state of the native liver is a key but not invariable prognostic factor. However, only cirrhosis is really detrimental and we lack real histological precision in defining this.
- Increasing age is certainly detrimental but realistically only if >80 days or the BA is clearly developmental (BASM and cystic BA).
- BA with associated anomalies has a worse outcome though whether this is because of the association with cardiac anomalies or it has an intrinsically worse outcome is not known.
- Type 1 BA and Cystic BA have the best outcome.
- Who does the operation. This is a rare disease and the porta hepatis is unfamiliar territory to most pediatric surgeons.
Centralization of resources for this disease has been adopted in many countries outside North America (e.g. UK, Finland, Netherlands).
What are the key outcome measures for Kasai Portoenterostomy?
- Median age at KPE—this reflects how quickly infants are referred in and delays in diagnosis—it should be 50–60 days;
- Proportion to clear jaundice after KPE (to normal levels <20 μmol/L or <1.5 mg/dL)—it should be >50% and values of >60–70% are possible;
- Native liver and true survival at 5 and 10 years. The former should be 45–50% with little change by 10 years, the second reflects the ease of access to safe transplantation.
Blood samples were taken from a 2 day old jaundiced neonate. Total bilirubin was 12mg/dL with a direct bilirubin of 1mg/dL. What would be the next step?
A. Coombs test
B. Phototherapy
C. Exchange transfusion
D. Biliary ultrasound
B. Phototherapy
Regarding the type and classification of biliary atresia, which of the following is false?
A. Type I atresia at porta is the most common.
B. Type I is the obliteration of the common bile duct, while the proximal bile ducts are patent.
C. Type IIa is atresia of the hepatic duct, with cystic bile ducts found at the porta hepatis.
D. Type IIb is atresia of the cystic duct, common bile duct, and hepatic ducts.
E. Type III is involvement of the extrahepatic biliary tree and intrahepatic ducts of the porta hepatis.
A
Type III atresia at portahepatis is the most common, about 88 percent.
Syed/MCQ
In preoperative management of biliary atresia, what is not required?
A. Chloretics
B. Antibiotic
C. Upper GIT contrast study
D. Metabolic and nutritional care
D. Essential fatty acid supplement
C
Upper GIT contrast study is generally not required.
Syed/MCQ
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Preoperative care:
1) Cephalosphorin+aminoglycoside 1 hr prior to OR, continued postoperatively until WBC resolved or CRP <0.3, or prophylactically if without cholangitis.
2) Vitamin K supplementation IV for several days prior.
3) Bowel prep glycerin enemas
4) NPO x 24 hrs
5) Broad spectrum antibiotics 1hr before skin incision.
6) Cholagogues ursocholic or aminoethylsulfuric at day 5 postop.
Select the best answer about the causes/cause of cholangitis after surgery for biliary atresia.
A. Portal venous infection
B. Destruction of lymphatics at porta hepatis
C. Bacterial translocation
D. All of the above
E. None of the above
D
All of the above.
Syed/MCQ
Regarding complications of surgery for biliary atresia, which of the following statements is false?
A. Cholangitis
B. Portal hypertension
C. Stricture of anastomosis
D. Leakage of anastomosis and peritonitis
E. None of the above
E
A, B, C and D all statements are true.
Syed/MCQ
The best answer among the following regarding differential diagnosis of biliary atresia is:
A. Biliary hypoplasia
B. Choledochal cyst
C. Inspissated bile syndrome
D. Neonatal jaundice
E. All of the above
E
Differential diagnosis also includes neonatal hepatitis, acquired obstruction like external pressure or stone, glycogen storage disease, lysosomal storage disease, G6PD deficiency and hemolytic disease.
Syed/MCQ
Regarding the management of biliary atresia, which of the following is false?
A. Preoperative presence of the gallbladder is an indication for cholangiography.
B. Preoperative gallbladder is used as a guide.
C. In Roux-en-y portoenterostomy, a 20cm Roux-en-y loop, 10cm distal to the duodenal junction is used.
D. Preoperative biopsy is taken from the right lobe.
E. If biopsy shows ductiles >150micro-m, this indicates a good prognosis.
C
20 cm loop is too short; about 40 cm loop of jejunum is used.
Syed/MCQ
What is the etiology of biliary atresia?
The exact etiology of biliary atresia is unknown and likely multifactorial. Theories implicating genetic, inflammatory, and infectious causes have been presented, but none has been proven.
The higher incidence of biliary atresia in certain populations makes a genetic cause plausible. Moreover, the observation that up to 20% of biliary atresia cases are associated with other congenital malformations implies a global developmental abnormality that may be under genetic control. Despite this, the occurrence of biliary atresia in twins is exceedingly rare, familial patterns have not been seen, and a clear genetic cause has not been found.
Theories suggesting an acquired, infectious etiology are supported by several findings. First, several viruses such as reovirus and rotavirus have been proposed as possible infectious agents responsible for the development of biliary atresia. Animal models of perinatal viral infection produce biliary atresia, although consistent viral isolation has not been possible in human cases. In addition, given the high prevalence of these viruses, it would be expected that the incidence of biliary atresia would be higher if, in fact, viral infection was causative.
Second, it appears that many cases of biliary atresia are acquired rather than congenital. Up to 60% of infants who are found to have biliary atresia have been documented as having pigmented stools sometime during the postnatal period.
Third is the epidemiologic finding of seasonal clustering of biliary atresia cases during the winter months in some studies.
Other proposed factors associated with biliary atresia include bile duct ischemia, abnormal bile acid metabolism, pancreaticobiliary maljunction, and the effect of certain environmental toxins.
[Coran]
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Various etiologic mechanisms for BA have been proposed, including intrauterine or perinatal viral infection, immunologically mediated inflammation and other autoimmune/ genetic factors, exposure to toxins, abnormal ductal plate remodeling, a vascular or metabolic insult to the developing biliary tree, and pancreaticobiliary malunion. Kilgore and Mack reported the most recent investigations into the pathogenesis of BA.
Reovirus type 3 infection, rotavirus, CMV, papillomavirus, and Epstein–Barr virus have all been proposed as possible etiologic agents, but conclusive evidence is lacking. In one report, CMV infection was found in 4 of 10 patients with BA, and reovirus infection has been found in the livers of up to 55% of patients with BA versus 10–20% in a control group. Evidence for a viral etiology in children with BA is inconsistent in the literature, although several viruses have been used to create animal models that may be valuable for assessing the pathogenesis and treatment of BA.
Generally, BA is not considered an inherited disorder. However, genetic mutations that result in defective morphogenesis may be important in syndromic BA that is associated with other congenital anomalies, including interrupted inferior vena cava, preduodenal portal vein, intestinal malrotation, situs inversus, cardiac defects, and polysplenia, likely due to a developmental insult occurring during differentiation of the hepatic diverticulum from the foregut of the embryo. Mutations of the CFC1 gene, which is involved in left–right axis determination in humans, have been identified in a few patients with syndromic BA.
Transgenic mice with a recessive deletion of the inversin gene have situs inversus and an interrupted extrahepatic biliary tree. The importance of the macrophage migration inhibitory factor gene, which is a pleiotropic lymphocyte and macrophage cytokine in BA pathogenesis, also has been reported. Other studies have identified abnormalities in laterality genes in a small number of patients with BA, including the transcription factor ZIC3. A high incidence of polymorphic variants in the jagged-1, keratin-8, and keratin-18 genes have also been described in a series of 18 children with BA. Taken together, the increased incidence of nonhepatic anomalies in children with BA and genetic mutations reported in subsets of patients with laterality defects suggest that multiple genes are involved, each affecting a small number of patients.
Intrahepatic bile ducts are derived from primitive hepatocytes that form a sleeve (the ductal plate) around the intrahepatic portal vein branches and associated mesenchyme early in gestation. Remodeling of the ductal plate in fetal life results in the formation of the intrahepatic biliary system. This is supported by similarities in cytokeratin immunostaining between biliary ductules in BA and normal first-trimester fetal bile ducts. These findings suggest that nonsyndromic BA might be caused by a failure of bile duct remodeling at the hepatic hilum, with persistence of fetal bile ducts poorly supported by mesenchyme.
Several studies have investigated whether bile duct epithelial cells are susceptible to an immune/inflammatory attack because of abnormal expression of human leukocyte antigens (HLAs) or intracellular adhesion molecules on their surfaces. A greater than threefold increase in the HLA-B12 antigen has been found in babies with BA compared with controls, particularly in those with no associated malformations. 51 Aberrant expression of class II HLA-DR antigens on biliary epithelial cells and damaged hepatocytes in patients with BA may render these tissues more susceptible to immune-mediated damage by cytotoxic T-cells or locally released cytokines. Increased expression of intercellular adhesion molecule-1 (ICAM-1) has been noted on bile duct epithelium in patients with BA, a finding that may play a role in immune-mediated damage. Strong expression of ICAM-1 also has been found on proliferating bile ductules, endothelial cells, and hepatocytes in BA. A direct relationship exists between the degree of ductal expression of ICAM-1 and disease severity, suggesting that ICAM-1 might be important in the development of cirrhosis.
Interest has also focused on co-stimulatory molecules. Two processes are involved in the activation of Tlymphocytes by antigen-presenting cells. One relates to the expression of major histocompatibility complex class II molecules, which interact directly with T-cell receptors. The other depends on the expression of B7 antigens on antigen-presenting cells and provides the second (costimulatory) signal to T-lymphocytes through CD28. In postoperative BA patients with good liver function, co-stimulatory antigens (B7-1, B7-2, and CD40) are expressed only on bile duct epithelial cells, whereas in patients with failing livers these markers are found on the surfaces of Kupffer cells, dendritic cells, and sinusoidal endothelial cells, and in the cytoplasm of hepatocytes. This finding suggests that the biliary epithelium and hepatocytes in BA are susceptible to immune recognition and destruction. Agents that block or prevent co-stimulatory pathways might offer a new therapeutic approach for reducing liver damage.
Two studies have involved comprehensive molecular and cellular surveys of liver biopsies and found a proinflammatory gene expression signature, with increased activation of interferon-γ, osteopontin, tumor necrosis factor-α, and other inflammatory mediators. These studies may prove to be helpful in delineating the molecular networks responsible for the proinflammatory response and autoimmunity thought to be involved in the pathogenesis of BA. However, none of these mechanisms appear to be mutually exclusive, and it is not clear which signs and symptoms are primary and which are secondary.
Most recently, DNA hypermethylation of Foxp3 was reported in BA infants, as well as a mouse model of BA. Klemann et al. showed that γδ T-cells were high producers of interleukin-17 (IL-17), and blocking IL-17 resulted in decreased liver inflammation and serum bilirubin levels. Furthermore, liver tissue from patients with BA at diagnosis had significantly increased levels of IL-17 mRNA. Lages et al. showed that CD4+ T cells were primarily responsible for IL-17 production and IL-17 stimulated macrophage influx and biliary injury in a mouse model.
In summary, the etiology of BA remains unknown. However, current research suggests there is a complex interplay of genetic predisposition, virus triggers, and progressive autoimmunity, culminating in bile duct injury, fibrosis, and biliary cirrhosis. A clearer understanding of the factors associated with bile duct epithelial injury will provide a framework for future targeted therapeutic interventions aimed at protecting the intrahepatic biliary system from ongoing injury.
[Holcomb and Ashcraft]
What is the embryology of the biliary system?
The biliary system originates from the hepatic diverticulum of the foregut at 4 weeks of gestation.
This structure differentiates into cranial and caudal components, which give rise to the intrahepatic and extrahepatic bile ducts, respectively.
It is during this period that the bile ducts undergo recanalization, eventually leading to an intact biliary tree.
Errors in the recanalization process constituted early theories regarding the etiology of biliary atresia, but this is no longer believed to be correct.
[Holcomb and Ashcraft]
What are the expected histopathologic findings for biliary atresia?
Early in the course of BA, the liver becomes enlarged, firm, and green. The gallbladder may be small and filled with white mucus, or it may be completely atretic.
Microscopically, the biliary tracts contain inflammatory and fibrous cells surrounding minuscule ducts, which are probably remnants of the original embryonic duct system.
The liver parenchyma is fibrotic and shows signs of cholestasis.
Proliferation of biliary neoductules is seen.
This process develops into end-stage cirrhosis if adequate biliary drainage does not occur.
These early changes are often nonspecific and may be confused with neonatal hepatitis and metabolic diseases.
It is generally accepted that the pathologic changes seen in BA are panductal, affecting the intrahepatic biliary tree as well as the extrahepatic bile duct system.
Intrahepatic bile ducts may be narrowed, distorted, or irregular.
Proliferation most likely results from disturbances in formation of the ductal plate as well as ductular metaplasia of hepatocytes.
Some authors think damage to the extrahepatic biliary system is a secondary phenomenon caused by obliteration. This theory is strongly supported by the fact that outcome is better if hepatic portoenterostomy is performed early.
The intrahepatic biliary tree is important not only pathologically, but also clinically.
The degree of damage that has already occurred in the intrahepatic biliary system is actually responsible for much of the morbidity after hepatic portoenterostomy.
[H&A]
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The pathologist plays a central role in the diagnosis of biliary atresia and provides an Important assessment of structures present at the fibrous biliary remnant.
Inflammation is invariably seen in liver biopsies and in resected specimens.
In the appropriate clinical scenario, a percutaneous liver biopsy can reliably aid in the diagnosis of biliary atresia.
The finding of bile ductular proliferation in the liver biopsy is considered diagnostic for biliary atresia.
Associated findings often include bile stasis, periportal inflammation, identification of giant cells, and varying degrees of fibrosis.
Histologic evaluation of the fibrous remnant can reveal patency or partial patency of ductal structures or complete absence of these structures. This may depend on whether excision of the remnant occurred before or after inflammatory obliteration of the extrahepatic ducts.
Identifiable structures that can be found in the biliary remnant include bile ducts, collecting ductules, and biliary glands. Of these, the ductules are ultimately responsible for bile drainage after the portoenterostomy procedure and, over time, these can form stable bile conduits.
[Coran]