Chapter 18 –Metabolic Liver Disease - NEONATAL CHOLESTASIS

Question 1

What is neonatal cholestasis?

Answer 1

Prolonged conjugated hyperbilirubinemia in the neonate, termed neonatal cholestasis, affects
approximately 1 in 2500 live births.

Question 2

The major conditions causing neonatal cholestasis?

Answer 2

• (1) cholangiopathies, primarily biliary atresia (discussed later), and
• (2) a variety of disorders causing conjugated hyperbilirubinemia in the neonate, collectively referred to as neonatal hepatitis.

Question 3

Neonatal cholestasis and hepatitis are not specific entities, nor are the disorders necessarily
inflammatory

T or F

Answer 3

TRUE

Instead, the finding of “neonatal cholestasis” should evoke a diligent search for recognizable toxic, metabolic, and infectious liver diseases, the more common of which are
listed in Table 18-7 .

Once identifiable causes have been excluded, one is left with the syndrome of “idiopathic” neonatal hepatitis, which shows considerable clinical overlap with biliary atresia.

Question 4

What is the most common of neonatal cholestasis?

Answer 4

Despite the long list of disorders associated with neonatal cholestasis, most are
quite rare.

• “Idiopathic” neonatal hepatitis represents as many as 50% of cases,
• biliary atresia represents another 20%, and
• α1-antitrypsin deficiency represents 15%.

Question 5

Why does Differentiation of biliary atresia from nonobstructive neonatal cholestasis assumes great importance?

Answer 5

since definitive treatment of biliary atresia requires surgical intervention (Kasai procedure), whereas surgery may adversely affect the clinical course of a child with other disorders.

Fortunately, discrimination can be made with clinical data in about 90% of cases, with or without liver biopsy.

Affected infants have jaundice, dark urine, light or acholic stools, and hepatomegaly.

Variable degrees of hepatic synthetic dysfunction may be identified, such as hypoprothrombinemia.
Thus, liver biopsy is critical in distinguishing neonatal hepatitis from an identifiable
cholangiopathy

Question 6

What is the critical in distinguishing neonatal hepatitis from an identifiable
cholangiopathy?

Answer 6

liver biopsy

Question 7

What are the clinical manifestation of Neonatal Cholestasis?

Answer 7

Affected infants have jaundice, dark urine, light or acholic stools, and hepatomegaly.

Variable
degrees of hepatic synthetic dysfunction may be identified, such as hypoprothrombinemia.

Question 8

TABLE 18-7 – Major Causes of Neonatal Cholestasis

Answer 8

• Bile duct obstruction
  
  • Extrahepatic biliary atresia
• Neonatal infection
  
  • Cytomegalovirus
  • Bacterial sepsis
  • Urinary tract infection
  • Syphilis
• Toxic
  
  • Drugs
  • Parenteral nutrition
• Metabolic disease
  
  • Tyrosinemia
  • Niemann-Pick disease
  • Galactosemia
  • Defective bile acid synthetic pathways
  • α1-Antitrypsin deficiency
  • Cystic fibrosis
• Miscellaneous
  
  • Shock/hypoperfusion
  • Indian childhood cirrhosis
  • Alagille syndrome (paucity of bile ducts)
• Idiopathic neonatal hepatitis

Question 9

What are the morphologic feature of neonatal hepatitis?

Answer 9

The morphologic features of neonatal hepatitis include lobular disarray with focal liver cell apoptosis and necrosis, panlobular giant-cell transformation of hepatocytes (Fig. 18-29 ), prominent hepatocellular and canalicular cholestasis, mild mononuclear
infiltration of the portal areas, reactive changes in Kupffer cells,and extramedullary
hematopoiesis.

This predominantly parenchymal pattern of injury may blend imperceptibly into a ductal pattern of injury, with bile ductular proliferation and fibrosis of portal tracts. In these cases distinction from an obstructive biliary atresia may therefore be difficult.

Question 10

Answer 10

FIGURE 18-29 Neonatal hepatitis. Note the multinucleated giant hepatocytes.

Question 11

END