Congenital Liver Disease Flashcards
A pediatric patient, less than 10 years, comes in complaining of jaundice, right upper quadrant pain and a palpable RUQ mass. What are you thinking?
- choledochal cyst
- The biliary tree can demonstrate a variety of structural abnormalities.
- One of the most common is choledochal cyst, which is a dilation of the biliary tree.
- Most cases present before the age of 10 years with jaundice and abdominal pain.
- The classic triad of presenting symptoms, seen in 40% of patients, is jaundice, abdominal pain, and a right upper quadrant mass.
what is jaundice and why are you concerned about it in the neonate?
Jaundice (icterus) refers to yellowish pigmentation of the skin and sclerae, and is due to abnormally high levels of bilirubin in the blood (hyperbilirubinemia).
- Jaundice is a common finding in the newborn period.
- The differential diagnosis of neonatal jaundice is long, and includes both completely innocuous causes and serious disorders requiring prompt recognition and therapy.
- Thus, the correct diagnosis of neonatal jaundice is very important.
What is physiologic jaundice? is it worrisome?
- Think of it as a symptom, that can be worsened by events like birth trauma, sepsis and hypoxia. However, those things are already “done” at birth. physiologic jaundice is common and not emergent.
- Many newborns experience a period of physiologic jaundice, which is related to an inability to adequately conjugate bilirubin.
- These infants have an elevated level of unconjugated bilirubin.
- The mechanism for conjugation of bilirubin is not mature until approximately 2 weeks of age. Additionally, during this time, increased bilirubin production occurs because of the breakdown of fetal red blood cells.
- prematurity is another factor that worsens physiologic jaundice
- Additionally, breast milk contains beta-glucuronidases, which deconjugate bilirubin glucuronides in the gut, also contributing to increased jaundice.
- Physiologic jaundice is usually self-limited but phototherapy can be used. Phototherapy transforms bilirubin into isomers, which can be excreted in bile and urine.
When you see elevated levels of conjugated bilirubin, what need you do to exclude problematic causes?
- Elevated levels of conjugated bilirubin in the neonate occur in approximately 1 in 2500 live births.
- Etiologies to be excluded include:
- infection (viral and bacterial),
- metabolic disorders (including alpha-1 antitrypsin deficiency, cystic fibrosis and metabolic storage disorders),
- bile duct obstruction (especially extrahepatic biliary atresia),
- and medication effects.
- Once these etiologies have been excluded, patients may fall into the category of idiopathic neonatal hepatitis; this classification is continually diminishing as specific etiologies are identified and defined.
what is the treatment for Biliary Atresia?
In the neonate setting = BA = biliary atresia
- Treatment includes hepatoportoenterostomy, also known as the Kasai Procedure.
- In this procedure, the extrahepatic biliary system is excised and a loop of small bowel is connected to the hepatic hilum to allow for bile drainage. The success of this procedure decreases after day of life 60.
- Therefore bile duct obstruction should be considered and excluded in all infants with persistent neonatal cholestasis.
What is Biliary Atresia?
Biliary Atresia is an important cause of neonatal cholestasis.
- Two forms are described. The perinatal form is more common and accounts for 65-90% of cases. In this disorder, the extrahepatic biliary tree is normal at birth and undergoes progressive destruction.
- Patients are usually of normal birth weight and have normal post birth weight gain; however, they develop late onset jaundice with progressively acholic stools.
- Most commonly, atresia of the entire extrahepatic biliary system is present.
- Proposed etiologies include infection, toxin, autoimmune destruction (in a neonate? huh.), and underlying genetic lesions.
- Histological findings on liver biopsy include: cholestasis in hepatocytes, canaliculi, and bile ducts; portal fibrosis with prominent bile duct proliferation; variable inflammation.
- These histologic findings are suggestive of BA; however, definitive diagnosis requires a cholangiogram to assess the patency of the biliary tree.
How do you arrive at a dx of biliary atresia?
- Histological findings on liver biopsy include: cholestasis in hepatocytes, canaliculi, and bile ducts; portal fibrosis with prominent bile duct proliferation; variable inflammation.
- These histologic findings are suggestive of BA; however, definitive diagnosis requires a cholangiogram to assess the patency of the biliary tree.
what is the less common cause and presentation of biliary atresia?
- most common cause is normal at birth with subsequent destruction
- The less common embryonic/fetal form of biliary atresia (10-35% of cases) probably represents a congenital structural anomaly of the biliary tree, and is usually associated with other congenital anomalies. In this form, infants develop progressive jaundice immediately after birth.
What can happen after the Kasai procedure?
The success of the procedure is limited by intrahepatic progression of disease and infection. Patients often progress to cirrhosis and require liver transplantation for long-term survival. Biliary atresia is the number one pediatric disorder requiring liver transplantation.
If you can’t find a definite etiology, what is the dx of exclusion for neonatal liver problems?
25-40% of infants with conjugated hyperbilirubinemia continue to have an undiagnosed etiology and may be categorized as having idiopathic neonatal hepatitis.
- Over 85% of cases are sporadic and 10-15% familial.
- Patients usually exhibit hepatomegaly and conjugated hyperbilirubinemia without a definable etiology.
- Findings on liver biopsy show cholestasis, prominent giant cell transformation of hepatocytes, minimal inflammation, and normal bile ducts.
You see: *Findings on liver biopsy show cholestasis, prominent giant cell transformation of hepatocytes, minimal inflammation, and normal bile ducts.
you should be thinking idiopathic neonatal hepatitis.
What’s up with TPN (Total Parenteral Nutrition) hepatopathy?
TPN (Total Parenteral Nutrition) hepatopathy is seen in the context of disease requiring more than short-term administration of TPN.
- The most common contexts are gastrointestinal diseases, such as congenital anatomic defects of the GI tract and necrotizing enterocolitis.
- The risk and severity are roughly proportional to duration of TPN therapy.
- Biopsy findings are similar to, and can be indistinguishable from, those in biliary atresia. The majority of cases will resolve once TPN is discontinued, but some patients can progress to cirrhosis.
What genetic condition can lead to unconjugated hyperbilirubinemia?
Unconjugated hyperbilirubinemia:
- Crigler –Najjar Syndrome: A genetic mutation leads to lack of (Type I) or decrease in (Type II) UDP-glucuronyltransferase (UGT1A1), which normally conjugates bilirubin to glucuronic acid, thus making water-soluble bilirubin glucuronides, which are excreted in bile.
- Bile contains only trace amount of unconjugated bilirubin.
- Serum unconjugated bilirubin levels are extremely high in these conditions
- Type I is fatal without liver transplantation. Patients with Type II have jaundice, but are otherwise asymptomatic, and can have a normal life expectancy.
What is the disorder that causes CYCLICAL unconjugated hyperbilirubinemia?
-Gilbert Syndrome: Patients have mild, benign fluctuating levels of serum bilirubin due to a decrease in UGT1A1 activity. Patients experience episodic jaundice, often during periods of physiologic stress such as illness.
What is a genetic disorder that causes CONJUGATED hyperbilirubinemia?
- Dubin-Johnson Syndrome: Results from hereditary defect in excretion of bilirubin glucuronides across the canalicular membrane due to absence of multidrug resistance protein 2.
- Patients may have episodic jaundice, but most have normal life expectancy.
