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LIVER DISORDERS

NEONATAL CHOLESTATIC JAUNDICE

Key clinical features of disorders causing prolonged neonatal cholestasis are (1) jaundice with elevated serum conjugated (or direct) bilirubin fraction (> 1.0 mg/dL and > 20% of total bilirubin), (2) variably acholic stools, (3) dark urine, and (4) hepatomegaly.

Neonatal cholestasis (conditions with decreased bile flow) is caused by both intrahepatic and extrahepatic diseases. Specific clinical clues (Table 22–1) distinguish these two major categories of jaundice in 85% of cases. Patients with intrahepatic cholestasis frequently appear ill and fail to thrive, whereas infants with extrahepatic cholestasis (biliary atresia [BA]) typically do not appear ill, have stools that are usually completely acholic, and have an enlarged, firm liver. Histologic examination of percutaneous liver biopsy specimens increases the accuracy of differentiation to 85%–95% (Table 22–2).

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Table 22–1. Characteristic clinical features of intrahepatic and extrahepatic neonatal cholestasis.
Intrahepatic Extrahepatic
Preterm infant, small for gestational age, appears ill Full-term infant, seems well
Hepatosplenomegaly, other organ or system involvement Hepatomegaly (firm to hard)
Stools with some pigment Acholic stools
Associated cause identified (infections, metabolic, familial, etc) Polysplenia or asplenia syndromes, midline liver

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Table 22–2. Characteristic histologic features of intrahepatic and extrahepatic neonatal cholestasis.
  Intrahepatic Extrahepatic
Giant cells +++ +
Lobules Disarray Normal
Portal reaction Inflammation, minimal fibrosis Fibrosis, lymphocytic infiltrate
Neoductular proliferation Rare Marked
Other Steatosis, extramedullary hematopoiesis, iron deposition Portal bile duct plugging, bile lakes

INTRAHEPATIC CHOLESTASIS

ESSENTIALS OF DIAGNOSIS & TYPICAL FEATURES

  • Elevated total and conjugated bilirubin.

  • Hepatomegaly and dark urine.

  • Patency of extrahepatic biliary tree.

General Considerations

Intrahepatic cholestasis is characterized by impaired hepatocyte secretion of bile and patency of the extrahepatic biliary system. A specific cause can be identified in about 60%–80% of cases, the remainder being labeled as idiopathic neonatal hepatitis or transient neonatal cholestasis. Patency of the extrahepatic biliary tract is suggested by pigmented stools and lack of bile duct proliferation and portal tract bile plugs on liver biopsy. Patency can also be determined, when clinically indicated, by cholangiography carried out either intraoperatively, percutaneously by transhepatic cholecystography, or by endoscopic retrograde cholangiopancreatography (ERCP) using a pediatric-size side-viewing endoscope. Magnetic resonance cholangiopancreatography (MRCP) in infants is of limited use and highly dependent on the operator and equipment.

1. Perinatal or Neonatal Hepatitis Resulting from Infection

This diagnosis is considered in infants with jaundice, hepatomegaly, vomiting, lethargy, fever, and petechiae. It is important to identify perinatally acquired viral, bacterial, or protozoal infections (Table 22–3) as they may be treatable. Infection may occur transplacentally, by ascent through the cervix into amniotic fluid, from swallowed contaminated fluids (maternal blood, urine, vaginal secretions) during delivery, from blood transfusions administered in ...

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