|Year : 1996 | Volume
| Issue : 1 | Page : 44-49
|Extrahepatic biliary atresia
Frederick J Suchy
Department of Pediatrics, Pediatric Gastroenterology, Hepatology Section, Yale University School of Medicine, New Haven, Connecticut, USA
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| Abstract|| |
Extrahepatic biliary atresia is a disease of unknown cause, leading to profound cholestasis and progressive biliary cirrhosis. This paper discusses the diagnosis and management of this condition. It is stressed that bile flow can be established in 80-90% of infants referred to surgery within 60 days after birth. Liver transplantation is essential for infants who are referred late (120 days of age or later); those whose initial portoenterostomy was not successful, and those who develop end-stage liver disease in spite of bile drainage.
|How to cite this article:|
Suchy FJ. Extrahepatic biliary atresia. Saudi J Gastroenterol 1996;2:44-9
Extrahepatic biliary atresia is a disease of the infant, in which all, or'part of the extrahepatic bile duct is destroyed or absent leading to profound cholestasis and progressive biliary cirrhosis ,, . Although the diagnosis is relatively uncommon, occurring in 1:10,000 to 1:15,000 live births, it accounts for about one third of neonates referred for evaluation of cholestasis, and is the single, most frequent cause of death from liver disease and indication for liver transplantation (-50% of all cases) in children  .
Extrahepatic biliary atresia is generally, not thought to be inherited. HLA identical twins discordant for biliary atresia have been described in several reports ,, . However, over 32 cases of the disorder have been reported in 14 families , . In possible familial cases "hypoplasia" of the common duct associated with severe intra hepatic cholestasis must be rigorously excluded. Cases in stillbirths or in premature infants are very rare. A significant increase in HLA B12 antigen has been found among biliary atresia patients without associated anomalies (23 of 47); a rate 3.23 times than seen in controls. The haplotypes A9-B_5 and A28-B35 were also found more frequently , .
Biliary atresia occurs more commonly in females than males ,,, . Most infants are full term and of normal birth weight. The perinatal course is typically unremarkable. Postnatal weight gain and development are initially normal. Jaundice is observed by the parents or the physician following the period of physiologic hyperbilirubinemia. The possibility of hepatobiliary disease must be considered in any neonate jaundiced beyond 14 days of age  .
Stools, are acholic at presentation; but early in the course, with evolving bile duct obstruction, stools are normally pigmented or only intermittently pigmented.
The liver is enlarged with a firm edge  . Splenomegaly is usually not present, but can evolve within months as portal hypertension develops. Ascites and edema are not common, but bleeding, secondary to the coagulopathy of vitamin K deficiency, may occur.
Laboratory studies are not diagnostic. Values in biliary atresia overlap with those found in patients with intrahepaticcholestasis ,, . Serum bilirubin levels range between six and 12 mg/dl with -50% of the total conjugated. Serum aminotransferase levels are slightly to moderately elevated. Serum alkaline phosphatase and 5' nucleotidase levels are also increased. Serum gammaglutamyltranspeptidase levels greater than 300 IU/I suggest a diagnosis of biliary atresia, whereas, lower values are more compatible with intrahepatic cholestasis  .
| Etiology|| |
The etiology of extrahepatic biliary atresia has not been established despite considerable investigation. There is no evidence, even in cases with other congenital anomalies, that biliary atresia results from a failure in morphogenesis or recanalization of the extrahepatic bile ducts during embryonic development  . In the majority of infants, obstructive obliteration of the biliary tract occurs postnatally  . Extrahepatic anomalies are present in 10-25% of patients and include cardiovascular defects, polysplenia, preduodenal or absent portal vein, malrotation, situs inversus, and bowel atresias , . A rare fetal type of biliary atresia has also been described in which congenital malformations occur more commonly and cholestatic jaundice is present from birth. A bile duct remnant can not be identified at the time of exploratory laparotomy in patients with this variant of biliary atresia , .
Numerous mechanisms have been proposed to account for the progressive obliteration of the extrahepatic biliary tree , . There is little support for an ischemic or toxic origin of extrahepatic bile duct injury. No abnormal toxic bile acid metabolite specific for the disorder has been identified. Congenital infections with cytomegalovirus, Epstein-Barr virus or rubella virus have been occasionally found, but the presence of these common agents may be coincidental ,,, . A possible role for reovirus type 3 has been proposed based upon serological evaluation of patients and controls  . Further evidence that reovirus type 3 may cause some cases of biliary atresia has come from immunolocalization of reovirus 3 antigens in a bile duct remnant of a patient with biliary atresia and by the apparent ability of reovirus 3 to produce extrahepatic biliary atresia in an infant rhesus monkey  . However, these serological data have not been confirmed by other workers  . In a recent study, a polymerase reaction assay was unable to detect reovirus 3 RNA in biliary tissue removed from 33 infants with biliary atresia  .
| Pathology|| |
The histological features most often found in biliary atresia are presented in [Table - 1]. The hepatic architecture is well preserved early in the course of the disease. Bile ductular proliferation is an important but variable finding suggestive of large duct obstruction. Bile plugs in the ducts of portal triads also indicate biliary obstruction. Canalicular and cellular bile stasis reflect the severity of the cholestasis. Portal tract fibrosis and edema are often present ,,,, . Swelling, vacuolization, and even sloughing of the biliary epithelium into the duct lumen may be seen. Portal tracts may be infiltrated with inflammatory cells. In about 25% of patients, giant cell transformation of hepatocytes to a degree more commonly found in neonatal hepatitis may be present. Bile ductules may be arrayed in a ductal plate pattern, suggesting that the disease has altered with the normal process of ductular remodeling, which occurs during prenatal development  . Biliary fibrosis or even cirrhosis may be found on presentation, or can develop during the first year of life with or without the successful restoration of bile flow.
The pathology of the extrahepatic bile ducts is variable , . A useful classification of the anatomic variants is based on the predominant site of the atresia  . Type I atresia involves obliteration of the common bile duct but the proximal ducts are patent. In Type II atresia, the hepatic duct is obstructed but, cystically-dilated bile ducts are found at the porta hepatis. In type IIa, the cystic and common ducts are patent, while in type IIb, these structures are also obliterated. These forms of biliary atresia have been referred to as "surgically correctable" but, unfortunately, comprise less than 10% of all patients with the disorder. Ninety percent or more of patients have type III atresia, involving obstruction of ducts at or above the porta hepatis. The entire perihilar area is encased in a cone of dense fibrous tissue. The gallbladder is involved, to some extent, in approximately 80% of patients. The type III variant has been referred to as "noncorrectable", in that there are no patent hepatic or dilated hilar ducts which can be used for a simple biliaryenteric anastomosis.
The fibrous remnant on microscopic examination shows complete fibrous obliteration of at least a portion of the extrahepatic bile ducts , . Bile ducts within the liver extending to the porta hepatis are initially patent during the first weeks of life but are progressively destroyed. The same process which damaged the extrahepatic ducts may be causal: the noxious effect of biliary obstruction is a contributing factor ,, . The intrahepatic biliary ducts may show variable degeneration of epithelial cells, inflammation, and periductular fibrosis.
In patients in whom laboratory, imaging and liver histology is unable to exclude biliary atresia, exploratory laparotomy and operative cholangiography are necessary to document the site of obstruction and properly direct attempts at surgical treatment ,,,, . Frozen sections of tissue from transsected porta hepatis can be evaluated for the presence and size of patent ducts. However, transsection of a biliary tree which is patent but small, because of biliary hypoplasia or severe intrahepatic cholestasis, should be avoided.
A simple anastomosis between patent proximal portions of the biliary system or cystic structures in the porta hepatis and a segment of bowel may be possible in approximately 10% of patients with the so-called "correctable" form of biliary atresia ,,,, . However, the hepatoportoenterostomy procedure developed by Kasai is necessary in the majority of cases with obliteration of the proximal extrahepatic biliary tree  . The fibrous common bile duct is excised above the bifurcation of the portal vein. The fibrous cone of tissue at the porta hepatis is transsected flush with the liver surface with the hope of exposing an area which may contain residual, microscopic bile ducts. A Rouxen-Y loop of jejunum is anastomosed to the bare edge of the transsected tissue to provide a conduit for biliary drainage. Many modifications of this original operation, most involving exteriorization of the Roux-en-Y loop with cutaneous bile diversion, have largely been abandoned. They were developed to decrease the high incidence of postoperative ascending cholangitis , , but there is no evidence that these procedures are effective. Severe fluid and electrolyte losses from the stoma and massive bleeding from peristomal varices were complications  . The original Kasai operation is now used by most pediatric surgeons to avoid these problems. Multiple attempts at revision of a nonfunctional hepatoportoenterostomy should also be avoided because subsequent adhesions resulting from multiple operations may make liver transplantation more difficult, if required at a later date.
| Prognosis|| |
The prognosis of untreated biliary atresia is extremely poor with death from liver failure usually occurring within two years. The hepatoportoenterostomy procedure can restore bile flow in most infants who undergo the procedure, but is rarely curative ,,,,,,,, . In a nationwide survey of major pediatric centers in Japan, only 325 of 2,013 patients survived for more than 10 years and only 157 (7.8%) remained jaundice-free with normal liver function  . A number of factors has now been identified which contribute to the variable outcome following hepatic portoenterostomy [Table - 2]. First, the age at which the operation is performed, has been found to be most critical ,,,,,,,, . Bile flow has been re-established in several recent series in 80 to 90% of infants, who were referred for surgery within 60 days after birth ,,, . In contrast, a success rate of less than 20% can be expected in infants who are 90 days of age or older at the time of surgery. In a U.S. series, predictors of a bad outcome were caucasian race, operative age greater than 60 days, the presence of cirrhosis on initial biopsy, totally nonpatent extrahepatic ducts, and absent ducts at the level of transsection in the liver hilus  . Bile duct profiles of 150 microns or greater, particularly if lined with columnar epithelium, have been associated by some workers with a good surgical result  . Schweizer recently found that prehilar bile duct structures of more than 400 microns were associated with a favorable prognosis  .
The severity of intrahepatic biliary cholangiopathy and the extent of hepatocyte injury are important determinants of prognosis ,,,,,, . Significant hepatocyte injury as indicated by lobular disarray and giant cell transformation has been also associated with a poor outcome  . Recurrent bouts of ascending bacterial cholangitis, which are most frequent during the first two years after operation, can contribute to the ongoing bile duct injury and can even lead to re-obstruction  (45). Infection is thought to spread by contiguous spread of organisms from the intestinal tract into patent biliary redicles. Blood cultures and cultures of liver tissue are positive in - 50% and - 30% of episodes, respectively.
Liver transplantation is essential in the management of extrahepatic biliary atresia [Figure - 1], and should be considered in patients whose operation is not successful in restoring bile flow, who are referred late (probably at 120 days of age or later), and who eventually, develop end-stage liver disease in spite of bile drainage ,,,,, The portoenterostomy may make liver transplantation more difficult technically, because of intraabdominal adhesions and the various enteric conduits which are sometimes encountered. However, despite increased blood loss and operative time, survival has not differed from children transplanted for other liver diseases. With the use of reduced-size allografts and living-related donors, rates of survival at one year has exceeded 90% in several series ,,.
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Frederick J Suchy
Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520
Source of Support: None, Conflict of Interest: None
[Figure - 1]
[Table - 1], [Table - 2]
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