Neonatal Cholestasis - An Overview

Introduction:

Neonatal cholestasis is the impaired bile flow from the liver into the intestine of the newborn. It is also known as idiopathic neonatal hepatitis and neonatal giant cell hepatitis. In this condition, liver cell functions are impaired. It is caused due to genetic diseases, viruses, and metabolic disorders. In addition, conjugated hyperbilirubinemia is present due to the failure of bilirubin excretion resulting in jaundice. It is usually seen in the first two weeks of a newborn's life. Hepatomegaly dark urine and acholic (lacking bile) stool are seen in infants. Laboratory investigations, liver biopsy, and hepatobiliary scans identify the disease. The treatment modalities are based on the cause and severity of the disease. Supportive care, along with fat-soluble vitamin supplementation, is given. In addition, a formula with medium-chain triglyceride is given to provide sufficient calories.

What Is Neonatal Cholestasis?

Neonatal cholestasis is the conjugated hyperbilirubinemia seen in newborns due to decreased bile flow. In this condition, the concentration of the serum-conjugated bilirubin is greater than 1 milligram per decilitre. The bile flow is reduced due to impaired secretion from hepatocytes or obstruction in intrahepatic and extrahepatic bile ducts. The disease's incidence is around one in two thousand term newborns. Neonatal cholestasis should be evaluated if the child is jaundiced for more than three weeks.

What Is the Pathophysiology of Neonatal Cholestasis?

Bile production is a two-step process in which hepatocytes uptake the bile acids from blood circulation, and the biliary canaliculus excretes the bile acids. Bile acid uptake from the blood occurs by the sinusoidal membrane of the hepatocytes. It requires Na taurocholate coin transporting polypeptide and organic anion transporting protein receptors. The receptors are also essential for the transport of toxins through the hepatocellular membrane of the liver. In neonates, the biliary system is functionally and structurally immature; therefore, the child is more susceptible to cholestasis. There is the primary failure of bilirubin excretion caused by excess conjugated bilirubin in the bloodstream. There is a decreased amount of bile salt in the gastrointestinal tract and inadequate bile in the gastrointestinal tract. Fat-soluble vitamins A, D, E, and K are malabsorption, causing growth failure and insufficient nutrition.

What Are the Causes of Neonatal Cholestasis?

The etiology of neonatal cholestasis is classified as intrahepatic and extrahepatic causes.

Extra-Hepatic Causes

• Biliary Atresia - There is progressive sclerosis of the bile duct, causing an obstruction. It manifests several weeks after birth. There is inflammation and scarring of the bile duct. It is usually seen in neonates and premature infants.

• Microorganism - Several microorganisms, such as rotavirus and cytomegalovirus, cause inflammation of the bile duct resulting in obstruction.

• Genetic Causes - The gene mutation interferes with bile production and excretion. Neonatal hepatic cholecystitis caused by to modification of a gene is also known as intrahepatic cholestasis. Autosomal recessive polycystic kidney diseases and biliary cysts also cause neonatal cholecystitis. Inspissated bile duct syndrome also causes bile duct obstruction resulting in neonatal cholestasis.

Intra-Hepatic Causes

• Infections - Bacterial and viral infection also results in neonatal cholecystitis. In addition, sepsis in newborns also causes neonatal cholestasis.

• Gestational Autoimmune Liver Diseases - During embryonic growth, maternal immunoglobulin G's transplacental passage induces complex complement-mediated membrane attacks. It results in injury in the fetal liver, causing neonatal cholestasis.

• Metabolic Causes - Inborn metabolic diseases such as galactosemia, tyrosinemia, and alpha-one antitrypsin deficiency also cause neonatal cholecystitis. Disorders of lipid metabolism, fatty acid oxidation defects, and bile acid defects also cause neonatal cholestasis.

• Toxic Causes - Prolonged parenteral nutrition to highly preterm infants results in neonatal cholestasis.

• Idiopathic Syndrome - It is an inflammatory condition of the newborn's liver. It is also known as giant cell hepatitis.

What Are the Clinical Features of Neonatal Cholestasis?

The signs and symptoms of the disease depend upon the severity of the disease. The clinical features are seen after two weeks of life. Listed below are the various clinical manifestations seen in children.

• Yellowish discoloration of eyes and skin.

• Dark urine containing conjugated bilirubin is seen.

• Acholic stool excretion.

• Hepatomegaly (increase in the size of the liver).

• Persistent cholestasis and chronic pruritis.

• Weight loss.

• Progression of growth is declined.

• Hepatic fibrosis (fibrous growth of the liver).

• Cirrhosis (scarring and permanent damage of the liver).

• Portal hypertension (increased pressure in the portal venous system).

• Abdominal distension.

• Ascites (collection of fluid in the spaces of the abdomen).

• Esophageal varices result in upper gastrointestinal bleeding.

• Dilated abdominal veins.

How Neonatal Cholestasis Diagnosed?

In newborns, if jaundice persists for more than two weeks, a diagnostic test for neonatal cholestasis should be performed. Evaluation of both direct and indirect bilirubin should be done. In addition, evaluation of albumin, serum bilirubin ammonia, prothrombin time, and partial thromboplastin time is indicated. Listed below are the various diagnostic evaluations shown in neonatal cholestasis.

• Liver Test.

• Direct and indirect bilirubin levels.

• Evaluation of fat-soluble vitamins E, D, A, and K.

• Ultrasonography examination of the liver.

• Hepatobiliary scan.

• Biopsy of the liver.

• Operative Cholangiography.

• Genetic Testing.

What Are the Treatment Plans for Neonatal Cholestasis?

The management of neonatal cholestasis depends upon the treatment of the cause. The treatment consists of supportive and nutritional therapy. If the infant is formula fed, formula with high concentration, medium chain triglyceride is given as its absorption is better. Vitamin supplements are given to the child. Ursodeoxycholic acid is given to the child twice for relief from itching. Surgical exploration is advised with an intraoperative cholangiogram if there is the presence of presumed biliary atresia. Portoenterostomy, also known as the Kasai procedure, is indicated. Exchange, transfusion, and treatment with immunoglobulin G are indicated in gestational autoimmune liver disease. Treatment for neonatal cholestasis is dependent on the underlying cause of the condition. Listed below are some common treatment options:

• Medications: Ursodeoxycholic acid may be used in some cases to dissolve the bile and improve liver function.

• Surgery: In cases where there is a blockage in the bile ducts, surgery may be necessary. This can involve removing the obstruction or creating a new pathway for bile to flow.

• Nutritional Support: Proper nutrition is essential for the baby's growth and development. Specialized formulas or feeding through a nasogastric tube may be necessary.

• Management of Complications: Additional treatment may be required if complications arise, such as liver failure or bleeding disorders. This could involve supportive measures such as blood transfusions.

• Liver Transplantation: A liver transplant may be necessary in severe cases where the liver is severely damaged.

Conclusion:

It is one of the newborns' most common causes of chronic liver disease. Early identification of the signs and symptoms of this disease and its etiology is essential for the proper prognosis. Proper diagnostic methods such as laboratory investigation, biochemical analysis, order imaging, and histopathology interpretation can help diagnose the disease. Proper nutritional support and vitamin supplementation are recommended along with the treatment. If left untreated, it can result in portal hypertension with a life-threatening situation. Newborn screening should be done, and parents should observe the signs and symptoms of the child. Regular visits to pediatricians should be maintained.