Biliary atresia

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Extrahepatic biliary atresia
Other namesExtrahepatic ductopenia
Intraoperative view of complete extrahepatic biliary atresia[1]
SpecialtyPediatric surgery Edit this on Wikidata
SymptomsJaundice, pale stool, dark urine
ComplicationsCirrhosis, portal hypertension, liver failure
TypesCongenital, acquired
TreatmentSurgery, liver transplantation
Frequency1 in 5,000 (East Asia), 1 in 10,000-15,000 (US)

Biliary atresia, also known as extrahepatic ductopenia and progressive obliterative cholangiopathy, is a childhood disease of the

acquired. It has an incidence of one in 10,000–15,000 live births in the United States,[2] and a prevalence of one in 16,700 in the British Isles.[3][4] Biliary atresia is most common in East Asia
, with a frequency of one in 5,000.

The cause of biliary atresia in Egyptian infants has been proven to be as a result of

Kasai procedure and liver transplantation.[10]

Signs and symptoms

Initially, the symptoms of biliary atresia are indistinguishable from those of neonatal jaundice, a usually harmless condition commonly seen in infants. However, infants with biliary atresia develop progressive conjugated jaundice, pale white stools, and dark urine. 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.[citation needed]

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

reovirus 3 has been proposed[12] and congenital cytomegalovirus infection,[13] as well. In addition autoimmune processes may contribute to pathogenesis in some cases as well.[14] However, with regard to these alternative causation the experimental evidence remains rather weak.[15]

Genetics

An association between biliary atresia and the

GPC1, which encodes a glypican 1-a heparan sulfate proteoglycan, has been reported.[16] This gene is located on the long arm of chromosome 2 (2q37) and is involved in the regulation of inflammation and the Hedgehog gene.[citation needed
]

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.[citation needed]

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.[17]

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[18] 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.[19]

Pathophysiology

There are three main types of extra-hepatic biliary atresia:[citation needed]

  • Type I: Atresia is restricted to the common bile duct.
  • Type II: Atresia of the common hepatic duct.
  • Type III: Atresia involves the most proximal part of the bile ducts (>95% of all cases).

In approximately 10% of cases, other anomalies may be associated with biliary atresia. The most common of these syndromic forms is BASM

hypersplenism, hepatorenal syndrome, and hepatopulmonary syndrome.[citation needed
]

In an Egyptian study, abnormally high levels of

TGF-beta, endothelin (ET), and nitric oxide (NO). Among these, TGF-beta is the most important pro-fibrogenic cytokine that can be seen in progressive cirrhosis.[citation needed
]

The cascade of immune involvement to remove damaged hepatocytes and cholangiocytes ushers regeneration. Yet in infants with biliary atresia regeneration is defective, and results in cirrhosis, as these infants have disrupted p53 and disrupted GSTPi. p53 and GSTPi are responsible for DNA fidelity at regeneration. Hence, these infants get accelerated cirrhosis and march to portal hypertension.[24]

Diagnosis

Diagnosis is made by an assessment of history, physical examination in conjunction with

Ultrasound or other forms of imaging such as radio-isotope liver scans can also be used but final confirmation is usually only reached at the time of exploratory surgery.[citation needed
]

Differential diagnoses

The

total parenteral nutrition-associated cholestasis.[25]

Treatment

Most (>95%) infants with biliary atresia will undergo an operation designed to retain and salvage the native liver, restore bile flow, and reduce the level of jaundice. This is known as the Kasai procedure (after Morio Kasai, the Japanese surgeon who first developed the technique) or hepatoportoenterostomy. Although the procedure is not thought of as curative, it may relieve jaundice and stop liver fibrosis, allowing normal growth and development. Published series from Japan, North America, and the UK show that bilirubin levels will fall to normal values in about 50-55% of infants, allowing 40-50% to retain their own liver to reach the age of 5 and 10 years (and beyond). Liver transplantation is an option for those children whose liver function and symptoms fail to respond to a Kasai operation.[citation needed]

Recent large-scale studies by Davenport et al. (Annals of Surgery, 2008) show that the age of the patient is not an absolute clinical factor affecting prognosis. The influence of age differs according to the disease etiology—i.e., whether biliary atresia is isolated, cystic (CBA), or accompanied by splenic malformation (BASM).[citation needed]

It is widely accepted that

antibiotics, has a beneficial effect on postoperative bile flow and can clear jaundice, but the dosing and duration of the ideal steroid protocol are controversial. Furthermore, it has been observed in many retrospective longitudinal studies that corticosteroid treatment does not seem to prolong survival of the native liver or transplant-free survival.[citation needed
]

Epidemiology

Biliary atresia seems to affect females slightly more often than males, and Asians and African Americans more often than Caucasians. It is common for only one child in a pair of twins or within the same family to have the condition. There seems to be no link to medications or immunizations given immediately before or during pregnancy. Diabetes during pregnancy particularly during the first trimester seems to predispose to a number of distinct congenital abnormalities in the infant such as sacral agenesis, transposition of the great vessels and the syndromic form of biliary atresia.[26]

References

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  5. ^ Kotb, Magd A.; Kotb, Ahmed (March 2015). "Extrahepatic Biliary Atresia is an Aflatoxin Induced Cholangiopathy in Infants with Null GSTM1 Genotype with Disrupted P53 and GSTPi to Mothers Heterozygous for GSTM1 Polymorphism: Damage Control is Mediated through Neutrophil Elastase and CD14+ Activated Monocytes: Kotb Disease" (PDF). The Medical Journal of Cairo University. 83 (2): 137–145.
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  17. ^ a b Kotb, Magd A. (March 2015). "Aflatoxins in Infants with Extrahepatic Biliary Atresia" (PDF). The Medical Journal of Cairo University. 83 (1): 207–210.
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  22. ^ Kotb, Magd A (March 2015). "Glutathione S Transferase M1 Polymorphism in Extrahepatic Biliary Atresia" (PDF). The Medical Journal of Cairo University. 83 (2): 109–112.
  23. ^ Kotb, Magd A (September 2014). "Nuetrophil Elastase Mediated Damage in Infants with Extrahepatic Biliary Atresia: A Prospective Cohort Study" (PDF). The Medical Journal of Cairo University. 82 (2): 233–237.
  24. ^ Kotb, Magd A. (March 2015). "Evidence of Disruption of p53 and Glutathione S Transferase Pi in Extrahepatic Biliary Atresia in Association with Neutrophil Elastase" (PDF). The Medical Journal of Cairo University. 83 (1): 201–205.
  25. ^ Pediatric Biliary Atresia~differential at eMedicine
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Further reading

External links
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