Biliary atresia is a
rare conditionA rare disease, sometimes known as an orphan disease, is any disease that is not common. Typically, a rare disease has such a low prevalence in a population that a physician in a busy general practice would not expect to see more than one case a year....
in newborn infants in which the common
bile ductA bile duct is any of a number of long tube-like structures that carry bile.Bile, required for the digestion of food, is excreted by the liver into passages that carry bile toward the hepatic duct, which joins with the cystic duct to form the common bile duct, which opens into the intestine.The...
between the
liverThe liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
and the
small intestineIn vertebrates, the small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where the vast majority of digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large...
is blocked or absent. If unrecognised, the condition leads to
liver failureAcute liver failure is the appearance of severe complications rapidly after the first signs of liver disease , and indicates that the liver has sustained severe damage . The complications are hepatic encephalopathy and impaired protein synthesis...
but not (as one might think) to
kernicterusKernicterus is damage to the brain centers of infants caused by increased levels of unconjugated-indirect bilirubin which is free . This may be due to several underlying pathologic processes. Newborn babies are often polycythemic, meaning they have too many red blood cells...
. This is because 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, or liver transplantation.
Initially, the symptoms are indistinguishable from neonatal jaundice, a common phenomenon.
Biliary atresia is a
rare conditionA rare disease, sometimes known as an orphan disease, is any disease that is not common. Typically, a rare disease has such a low prevalence in a population that a physician in a busy general practice would not expect to see more than one case a year....
in newborn infants in which the common
bile ductA bile duct is any of a number of long tube-like structures that carry bile.Bile, required for the digestion of food, is excreted by the liver into passages that carry bile toward the hepatic duct, which joins with the cystic duct to form the common bile duct, which opens into the intestine.The...
between the
liverThe liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
and the
small intestineIn vertebrates, the small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where the vast majority of digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large...
is blocked or absent. If unrecognised, the condition leads to
liver failureAcute liver failure is the appearance of severe complications rapidly after the first signs of liver disease , and indicates that the liver has sustained severe damage . The complications are hepatic encephalopathy and impaired protein synthesis...
but not (as one might think) to
kernicterusKernicterus is damage to the brain centers of infants caused by increased levels of unconjugated-indirect bilirubin which is free . This may be due to several underlying pathologic processes. Newborn babies are often polycythemic, meaning they have too many red blood cells...
. This is because 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, or liver transplantation.
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 phototherapy and/or
exchange transfusionsAn exchange transfusion is a medical treatment in which apheresis is used to remove one person's red blood cells or platelets and replace them with transfused blood products...
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
kernicterusKernicterus is damage to the brain centers of infants caused by increased levels of unconjugated-indirect bilirubin which is free . This may be due to several underlying pathologic processes. Newborn babies are often polycythemic, meaning they have too many red blood cells...
.
UltrasoundDiagnostic sonography is an ultrasound-based diagnostic imaging technique used to visualize subcutaneous body structures including tendons, muscles, joints, vessels and internal organs for possible pathology or lesions. Obstetric sonography is commonly used during pregnancy and is widely...
investigation or other forms of imaging can confirm the diagnosis. Further testing includes radioactive scans of the liver and a
liver biopsyLiver biopsy is the biopsy from the liver. It is a medical test that is done to aid diagnosis of liver disease, to assess the severity of known liver disease, and to monitor the progress of treatment.-History:...
.
Biliary atresia is a very rare disorder. About one in 10,000 to 20,000 babies in the U.S are affected every year. 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,
bileBile or gall is a bitter yellowish, blue and green fluid secreted by hepatocytes from the liver of most vertebrates. In many species, bile is stored in the gallbladder between meals and upon eating is discharged into the duodenum where the bile aids the process of digestion of lipids by...
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-1For the ICAO airport code see Candle Lake Airpark, for the diradical compound see Dichlorocarbene.Chemokine ligand 2 is a small cytokine belonging to the CC chemokine family that is also known as monocyte chemotactic protein-1 . CCL2 recruits monocytes, memory T cells, and dendritic cells to...
,
Tumor necrosis factor (TNF)Tumor necrosis factor is a cytokine involved in systemic inflammation and is a member of a group of cytokines that stimulate the acute phase reaction....
, Interleukin-6 (IL-6), TGF-beta,
Endothelin (ET)Endothelins are proteins that constrict blood vessels and raise blood pressure. They are normally kept in balance by other mechanisms, but when they are over-expressed, they contribute to high blood pressure and heart disease....
, and
nitric oxide (NO)Nitric oxide or nitrogen monoxide is a chemical compound with chemical formula NO. This gas is an important signaling molecule in the body of mammals, including humans, and is an extremely important intermediate in the chemical industry...
. 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
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
hepatoportoenterostomyA hepatoportoenterostomy, or Kasai procedure is a surgical treatment performed on infants with biliary atresia. In these infants, the bile is not able to drain normally from the small bile ducts within the liver into the larger bile ducts that connect to the gall bladder and small intestine...
.
If the atresia is complete,
liver transplantationLiver transplantation or hepatic transplantation is the replacement of a diseased liver with a healthy liver allograft. The most commonly used technique is orthotopic transplantation, in which the native liver is removed and the donor organ is placed in the same anatomic location as the original...
is the only option. Timely Kasai portoenterostomy (eg < 60 postnatal days) have 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) showed that age of the patient is not an absolute clinical factor affecting the prognosis. In the latter study, influence of the age is different according to the disease ethiologies such as isolated BA, BASM (BA with splenic malformation ), and CBA(cystic biliary atresia).
It is widely accepted that corticosteroid treatment after Kasai operation with/without choleretics and antibiotics have a beneficial effect on the postoperative bile flow and, thereby clear the jaundice of the patients, but the dose and duration of the ideal steroid protocol has 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 after Kasai operation has no effect of the mid and long term prognosis of the post-Kasai biliary atresia patients.
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