Biliary atresia Q44.2

Biliary atresia was first described towards the end of the 19th century after histopathological studies in children who died of liver disease.

In the 2nd half of the 20th century, two important advances were made therapeutically:

- Hepatic portoenterostomy according to Kasai in 1959 (Lentze 2003).

In this procedure, the extrahepatic biliary system is first removed and then replaced by a loop of intestine, the so-called Roux- en- Y- anastomosis, which is directly connected to the portal area of the liver.

- Liver Transplantation (Bezerra 2018).

This was first pioneered by Starzl in Denver in 1963. In Germany, the first liver transplantation was performed by Gütgemann et al. in Bonn in 1969 (Ghadimi 2022).

Biliary atresia is a hereditary form of cholangiopathy that can affect both extra- and intrahepatic bile ducts (Lendahl 2021).

Biliary atresia (BA) represents the most common cholangiopathy with clinical relevance (Kasper 2015).

According to Kasai, BA is classified into:

• I. Extrahepatic biliary atresia:
  • Type I: ductus choledochus affected.
  • Type II: ductus hepaticus communis affected
  • Type III: ductus hepatici affected
• II. Intrahepatic biliary atresia
• III: Bile duct hypoplasia (Herold 2022)

The classification according to Desmet includes the following clinical forms of biliary atresia:

• Fetal or embryonic type:

In this case, early neonatal cholestasis is found with continuous transition of physiological neonatal ictus. Bile duct residues in the hepatoduodenal ligament do not exist. Associated malformations are found in 10-20% of cases. The fetal type occurs in about 35% of patients with BA (Lentze 2003).

• Perinatal type:

This is characterized by late- onset cholestasis. After the neonatal icterus subsides, there is an icterus-free interval. Cholestasis occurs 10-21 days post partum. There are bile duct residues in the hepatoduodenal ligament, but there are no associated malformations. The perinatal type is found in approximately 65% of patients with BA (Lentze 2003).

The following anatomical variants of BA have also been described:

• Typical BA (approx. 80 %)
• BA with cystic dilatation of the bile duct (in approx. 5 - 10 %)
• BA with additional associated malformations such as congenital heart, urinary or gastrointestinal diseases, lateralization defects (in approx. 5 - 15 %)

(Bezerra 2018)

The incidence in Europe is 5 - 25: 100,000 live births. In Asia, Taiwan and Japan, it is significantly higher at 100 - 500: 100,000 live births (Lendahl 2021).

In female newborns, BA is found slightly more frequently than in male newborns (Bezerra 2018).

Genetic factors, immunological processes, and infections of the biliary system are suspected causes (Lentze 2003), as are possible exposures to hepatotoxins (Lendahl 2021).

The genetics of BA are complex, especially since most genetic forms are nonsyndromic Lendahl 2021). The genetic component appears to play a role only occasionally, as familial cases are rarely found and there is disease discrepancy even in identical twins (Bezerra 2018).

In viral exposure, intrauterine infections with e.g. cytomegalovirus, human papillomavirus, Epstein- Barr- virus play a role. For hepatotoxin exposure in the fetal stage, e.g., the plant toxin biliatresone may play a role (Lendahl 2021).

To date, the pathogenesis of BA is unknown (Bezerra 2018).

BA becomes clinically apparent early in infancy by:

- severe obstructive jaundice

- settling of pale stools (Kasper 2015)

- dark discoloration of the urine (Bezerra 2018)

The suspected diagnosis is made clinically, by laboratory chemistry and imaging, and possibly confirmed by surgical exploration and intraoperative cholangiography (Kasper 2015). However, the diagnosis is usually made between the 6th-12th week of life (Bezerra 2018).

To accelerate this, newborn screening for direct and conjugated bilirubin is being performed in the United States and shows promise (Harpavat 2020).

Universal stool color screening of infants has now been introduced in some countries to detect cases of BA early (Lendahl 2021).

Similarly, according to (He 2021), detection of the biomarker MMP7 in blood appears to have a high sensitivity and specificity of 95% each.

- Sonography

- Magnetic resonance cholangiography (MCR)

- Intraoperative cholangiography (Herold 2022)

- DECT examination:

Shang (2020) recommends preoperative DECT- examination to image the hepatic venous and arterial vessels.

Intracellular beta-amyloid deposits are detectable in the liver of patients with BA. In other diseases with beta-amyloid deposits, such as Alzheimer's disease and cerebral amyloid angiopathy [CAA], these deposits are found extracellularly (Lendahl 2021).

In approximately 10% of affected individuals, a Roux- en- Y- choledochojejunostomy can be used therapeutically (HPE [Bezerra 2018]), the so-called Kasai- procedure, a hepatic portoenterostomy, to restore bile flow (Herold 2022).

The success of the surgery depends on the age of the children. The best results, with 60-80% restoration of bile flow, are obtained when the operation is performed between the 30th and 45th day of life (Bezerra 2018).

However, the vast majority of patients who have received HPE develop chronic cholangitis with extensive liver fibrosis and portal hypertension over the years (Kasper 2015), ultimately requiring liver transplantation or liver segment transplantation from relatives (Herold 2022).

At least half of preoperated children require liver transplantation before 2 years of age and > 75% require transplantation before 20 years of age (Bezerra 2018).

In children, BA is their most common cause of liver transplantation (Kasper 2015).

The prognosis is unfavorable without transplantation (Herold 2022).

After transplantation, lifelong immunosuppression limits the quality of life of those affected (Lendahl 2021).

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