Some infants fail to thrive as there will be a degree of fat and fat-soluble vitamin malabsorption (e.g. Vitamin K). This may cause a bleeding tendency. Eventually, and usually after 2 months, cirrhosis with portal hypertension will develop. If left untreated, biliary atresia can lead to liver failure. Unlike other forms of jaundice, however, biliary-atresia-related cholestasis mostly does not result in kernicterus, a form of brain damage resulting from liver dysfunction. This is because in biliary atresia, the liver, although diseased, is still able to conjugate bilirubin, and conjugated bilirubin is unable to cross the blood–brain barrier. Causes
The cause of biliary atresia in most infants is not fully understood and it is well possible that a number of factors may play a role, but especially maternal rotavirus infection during pregnancy and subsequent transmission of the virus to the child resulting in infection of the biliary epithelium and subsequent occluding fibrosis may be important in this respect. Some cases may relate to infection with other viruses (including COVID-19) as well, for instance infection with the hepatotropic virus reovirus 3 has been proposed and congenital cytomegalovirus infection, as well. In addition autoimmune processes may contribute to pathogenesis in some cases as well. However, with regard to these alternative causation the experimental evidence remains rather weak. Genetics
An association between biliary atresia and the ADD3 gene was first detected in Chinese populations through a genome-wide association study, and was confirmed in Thai Asians and Caucasians.
A possible association with deletion of the gene GPC1, which encodes a glypican 1-a heparan sulfate proteoglycan, has been reported. This gene is located on the long arm of chromosome 2 (2q37) and is involved in the regulation of inflammation and the Hedgehog gene.Egyptian infants with biliary atresia were found to have null GSTM1 genotype while all their mothers were heterozygous for GSTM1. Thus these infants may be protected in utero by their maternal detoxification system, yet once born they cannot handle the detoxification of an aflatoxin load. Toxins
Some cases of biliary atresia may result from exposure to aflatoxin B1, and to a lesser extent aflatoxin B2 during late pregnancy. Intact maternal detoxification protects baby during intrauterine life, yet after delivery, the baby struggles with the aflatoxin in its blood and liver. Moreover, the baby feeds aflatoxin M1 from its mom, as aflatoxin M1 is the detoxification product of aflatoxin B1. It is a milder toxin that causes cholangitis in the baby.There are isolated examples of biliary atresia in animals. For instance, lambs born to sheep grazing on land contaminated with a weed (Red Crumbweed) developed biliary atresia at certain times. The plants were later found to contain a toxin, now called biliatresone Studies are ongoing to determine whether there is a link between human cases of biliary atresia and toxins such as biliatresone. There are some indications that a metabolite of certain human gut bacteria may be similar to biliatresone.