Neonatal Cholestasis

Cholestasis (see also Neonatal Hyperbilirubinemia Neonatal Hyperbilirubinemia Jaundice is a yellow discoloration of the skin and eyes caused by hyperbilirubinemia (elevated serum bilirubin concentration). The serum bilirubin level required to cause jaundice varies with... read more ) may result from extrahepatic or intrahepatic disorders, although some conditions overlap.

In cholestasis, the primary failure is of bilirubin excretion, resulting in excess conjugated bilirubin in the bloodstream and decreased bile salts in the gastrointestinal (GI) tract. As a result of inadequate bile in the GI tract, there is malabsorption Overview of Malabsorption Malabsorption is inadequate assimilation of dietary substances due to defects in digestion, absorption, or transport. Malabsorption can affect macronutrients (eg, proteins, carbohydrates, fats)... read more of fat and fat-soluble vitamins (A, D, E, and K), leading to vitamin deficiency, inadequate nutrition, and growth failure.

Cholestasis typically is noted in the first 2 weeks of life. Infants are jaundiced and often have dark urine (containing conjugated bilirubin), acholic stools, and hepatomegaly.

If cholestasis persists, chronic pruritus is common, as are symptoms and signs of fat-soluble vitamin deficiency; progression on growth charts may show a decline.

If the underlying disorder causes hepatic fibrosis and cirrhosis, portal hypertension with subsequent abdominal distention resulting from ascites, dilated abdominal veins, and upper GI bleeding resulting from esophageal varices may develop.

Any infant who is jaundiced after age 2 weeks should be evaluated for cholestasis including with total and direct bilirubin levels. Some experts advocate that breastfed infants who have jaundice do not need to be evaluated until age 3 weeks. The initial approach should be directed at diagnosing treatable conditions (eg, extrahepatic biliary atresia Diagnosis Biliary atresia is obstruction of the biliary tree due to progressive sclerosis of the extrahepatic bile duct. Diagnosis is by blood tests, ultrasonography, liver biopsy, and hepatobiliary scan... read more , in which early surgical intervention improves short-term outcome).

Cholestasis is identified by an elevation in both total and direct bilirubin. Tests that are needed to further evaluate the liver include albumin, fractionated serum bilirubin, liver enzymes, prothrombin time/partial thromboplastin time (PT/PTT), and ammonia level (see Tests for Cholestasis Tests for Cholestasis Laboratory tests are generally effective for the following: Detecting hepatic dysfunction Assessing the severity of liver injury Monitoring the course of liver diseases and the response to treatment... read more ).

Once cholestasis is confirmed, testing is required to determine etiology (see table ) and evidence of malabsorption Overview of Malabsorption Malabsorption is inadequate assimilation of dietary substances due to defects in digestion, absorption, or transport. Malabsorption can affect macronutrients (eg, proteins, carbohydrates, fats)... read more (eg, low levels of the fat-soluble vitamins E, D, K, and A, or prolonged PT, suggesting a low level of vitamin K).

Abdominal ultrasonography is often the first test; it is noninvasive and can assess liver size and certain abnormalities of the gallbladder and common bile duct. However, it is nonspecific. A hepatobiliary scan using hydroxy iminodiacetic acid (HIDA scan Cholescintigraphy Imaging is essential for accurately diagnosing biliary tract disorders and is important for detecting focal liver lesions (eg, abscess, tumor). It is limited in detecting and diagnosing diffuse... read more ) should also be done; excretion of contrast into the intestine rules out biliary atresia, but lack of excretion can occur with biliary atresia, severe neonatal hepatitis, and other causes of cholestasis. Infants with cholestasis are frequently given phenobarbital for 5 days prior to a HIDA scan in an attempt to enhance the excretion. In some tertiary pediatric centers, endoscopic retrograde cholangiopancreatography (ERCP Endoscopic retrograde cholangiopancreatography (ERCP) Imaging is essential for accurately diagnosing biliary tract disorders and is important for detecting focal liver lesions (eg, abscess, tumor). It is limited in detecting and diagnosing diffuse... read more ) can be done to investigate the anatomy of the biliary ductal system.

When no diagnosis has been made, a liver biopsy is generally done relatively early on, sometimes with operative cholangiography. Patients with biliary atresia typically have enlarged portal triads, bile duct proliferation, and increased fibrosis. Neonatal hepatitis is characterized by lobular disarray with multinucleated giant cells. Alloimmune liver disease is characterized by elevated hepatic iron stores.

Specific treatment is directed at the cause. If there is no specific therapy, treatment is supportive and consists primarily of nutritional therapy, including supplements of vitamins A, D, E, and K.

For formula-fed infants, a formula that is high in medium-chain triglycerides should be used because it is absorbed better in the presence of bile salt deficiency. Adequate calories are required; infants may need > 130 calories/kg/day. In infants with some bile flow, ursodeoxycholic acid once or twice a day may relieve itching.

Infants with presumed biliary atresia require surgical exploration with an intraoperative cholangiogram. If biliary atresia is confirmed, a portoenterostomy (Kasai procedure) should be done. Ideally, this procedure should be done in the first 1 to 2 months of life. After this period, the short-term prognosis significantly worsens. Postoperatively, many patients have significant chronic problems, including persistent cholestasis, recurrent ascending cholangitis, and failure to thrive. Prophylactic antibiotics (eg, sulfamethoxazole/trimethoprim, SMX-TMP, cotrimoxazole) are frequently prescribed for a year postoperatively in an attempt to prevent ascending cholangitis. Even with optimal therapy, most infants develop cirrhosis and require liver transplantation.

Cholestasis caused by parenteral nutrition resolves if the parenteral nutrition is stopped or sometimes if a newer-generation lipid emulsion is substituted for an older one before the infant develops severe liver disease.

Because gestational alloimmune liver disease has no definitive marker and/or test, treatment with IV immune globulin (IVIG) or exchange transfusion needs to be considered early to reverse the ongoing liver injury if no definite diagnosis has been made (1 Treatment reference Cholestasis is failure of bilirubin secretion, resulting in conjugated hyperbilirubinemia and jaundice. There are numerous causes, which are identified by laboratory testing, hepatobiliary scan... read more ).

Biliary atresia is progressive and, if untreated, results in liver failure, cirrhosis with portal hypertension by several months of age, and death by 1 year of age.

Prognosis for cholestasis due to specific disorders (eg, metabolic disease) is variable, ranging from a completely benign course to a progressive disease resulting in cirrhosis.

Idiopathic neonatal hepatitis syndrome usually resolves slowly, but permanent liver damage may result and lead to liver failure and death.

Gestational alloimmune liver disease has a poor prognosis without early intervention.

The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.