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Submitted By tcobra2012
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The liver is the largest and one of the most complex organs in the body. The normal liver is soft, smooth organ. It is located in the upper right portion of the abdomen, below the diaphragm, and extends slightly below the rib cage. It is connected to the small intestine by bile ducts. The liver is divided into two lobes that are further subdivided into segments.

There are two special features unique to the liver. First, blood is supplies primarily from the portal vein. This vein collects blood from all the digestive organs and channels it through the liver. Then the various nutrients are checked before they are distributed to the rest of the body. This process can expose the liver to high levels of any medicine that is taken by mouth, making the liver highly susceptible to drug-induced injury.

The second unique feature of the liver is the bile ducts, which transport bile from the liver to the small intestine. The liver cells (hepatocytes) produce a yellowish-green fluid (bile) that collects in the bile ducts. Bile contains special substances that help the body absorb fat and vitamins from the intestines. It also contains waste products collected from the blood.

Liver dysfunction occurs if: liver cell function is destroyed or impaired; bile ducts are destroyed or blocked; and/or blood flow to or from the liver is altered. Since injured liver cells cannot process and excrete waste products, including bilirubin, jaundice occurs. Bilirubin, a normal waste product derived from the breakdown of old red blood cells, indicates the severity of liver impairment. When too much bilirubin accumulates in the body, the patient’s skin turns a yellowish-green color, a condition known as jaundice. This is a common symptom of liver disease.

At Children’s, 308 primary liver transplants were performed between 1995 and 2006. Of these, 103, or 33 percent, were performed for biliary atresia. Overall patient survival and graft survival rates at more than 10 years were 88 percent and 81 percent, respectfully, among the highest long term survival rates in the world. These patients were enrolled in the Studies on Pediatric Liver Transplantation (SPLIT) — a multi-center, prospective study to collect scientific data on pediatric liver transplantation.

Surgical removal of the blocked main bile duct can buy time but ultimately the treatment in the majority of cases is a liver transplant during infancy or childhood, a procedure that is both complicated and expensive. Until now, doctors weren't sure what caused biliary atresia, which is important to know in order to develop better treatments. The CU researchers propose that an infection late in the third trimester of pregnancy or soon after birth initiates the bile duct injury.
The body fights off the infection and infants initially show no signs of a problem. But then, the body continues to battle as if the infection still was active. The body, however, is attacking itself -- the bile ducts specifically -- not the infection. This is called an autoimmune process.

Biliary atresia, which occurs once in every 15,000 births, is an irreversible problem that is fatal without treatment. However, surgical intervention, may allow a child with biliary atresia to live longer and have a better quality of life. In order to have optimal results, infants should undergo surgery before 2 months of age, necessitating early referral. Symptoms of biliary atresia occur between 2 weeks to 2 months of life, and may include: jaundice that persists beyond 3 weeks of age, dark urine, light colored stools and failure to thrive.

Biliary atresia is an idiopathic neonatal cholestatic disease characterized by the destruction of both the intra- and extra-hepatic biliary ducts. There are two clinical manifestations of the disease: an embryonic subtype, which often presents at birth and is associated with congenital malformations, and a 'prenatal' subtype, which is probably an acquired disease due to unknown etiology.

Over the last two decades, researchers have focused on activation of the cell-mediated immunity as the mechanism for biliary epithelial cell destruction for the latter subtype. A proposed trigger of this immune response is an initial viral infection, inducing biliary epithelial cells to become antigen-presenting cells and thus instigating immune-mediated destruction of the biliary tract.

However, putative viruses have never been confirmed. More recently, a novel hypothesis - that maternal microchimerism may initiate a host immunologic response towards the bile duct epithelia - has been proposed.

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