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NORD is very grateful to William F. Balistreri, MD, Director, Pediatric Liver Care Center, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, for assistance in the preparation of this report.
"Neonatal hepatitis" is a general term used to denote injury to the liver that occurs shortly after birth. Neonatal hepatitis may be caused by viruses, metabolic disease or genetic disorders, as well as other rare diseases that affect or impair the function of the liver. In some children, the cause of liver injury is unknown - these cases are referred to as idiopathic neonatal hepatitis (INH). The symptoms of idiopathic neonatal hepatitis may vary greatly from one individual to another. Symptoms common to liver disease often occur including yellowing of the whites of the eyes and the skin (jaundice), enlargement of the liver (hepatomegaly) and unusually dark urine. Most individuals with idiopathic neonatal hepatitis fully recover from the condition; however, some will progress to chronic liver disease.
The liver is located on the right side of the abdominal cavity just under the rib cage. The liver has many different functions including filtering harmful substances (toxins) out of the bloodstream, synthesizing proteins, storing essential vitamins, helping to breakdown (metabolize) food to use as energy, creating enzymes that help the blood form clots in response to injury, and producing bile, a liquid that plays an essential role in breaking down fats in the small intestine.
In many cases, the first sign of liver disease is yellowing of the whites of the eyes and the skin (jaundice). Some infants with idiopathic neonatal hepatitis may also have an enlarged liver (hepatomegaly). Additional signs that may occur include unusually dark urine and pale or clay-colored (acholic) stools.
The disorder can range from a mild, temporary (transient) disease that improves without treatment to more serious forms that cause additional complications. The common symptoms of liver disease may appear anytime during the first few weeks of life. By the age of 2 to 3 months, it becomes clear that an infant with neonatal hepatitis is not gaining weight and is growing at a slower than normal rate (failure to thrive). The infant may be irritable because of excessively itchy skin (pruritus). Other symptoms may include enlargement of the spleen (splenomegaly) and/or the accumulation of body fluids within the abdomen (ascites).
In more serious forms of neonatal hepatitis additional symptoms can occur including easy bruising, prolonged bleeding, and infection of the blood (sepsis). Liver (hepatic) failure may eventually develop in some individuals with severe forms of neonatal hepatitis.
Neonatal hepatitis, in general, has many different causes including several viruses including cytomegalovirus and the herpes viruses; various metabolic liver diseases or genetic disorders such as alpha-1-antitrypsin deficiency; rare disorders may also impair the function of the liver (cholestatic disorders).
By definition, the cause of idiopathic neonatal hepatitis is not known. Most cases are believed to occur randomly (sporadically). Idiopathic neonatal hepatitis is responsible for 10-25 % of infants with neonatal cholestasis - a common condition of newborns in which the flow of bile from the liver is reduced or blocked, resulting in jaundice.
According to the medical literature, 15-20 percent of cases of idiopathic neonatal hepatitis run in families (familial form) suggesting that genetic factors play a role in its development.
The incidence of idiopathic neonatal hepatitis in the general population is unknown. The proportion of cases classified as "idiopathic" has diminished as advanced diagnostic techniques and a better molecular understanding of cholestatic diseases in general have allowed physicians to diagnosis many infants with specific syndromes. In the past, these infants would have been included as having idiopathic neonatal hepatitis.
Symptoms of the following disorders can be similar to those of idiopathic neonatal hepatitis. Comparisons may be useful for a differential diagnosis.
Biliary atresia is a rare gastrointestinal disorder characterized by destruction or absence of all or a portion of the bile duct system. The bile duct is a series of tubes that allow the passage of bile from the liver into the gall bladder and, eventually, the small intestine. In patients with biliary atresia, absence or destruction of the bile ducts results in the abnormal accumulation of bile in the liver. Affected infants may have yellowing of the skin and whites of the eyes (jaundice) and scarring of the liver (cirrhosis). Additional symptoms may include itching, enlargement of the liver (hepatomegaly), pale, gray stools, and a swollen stomach. In some cases, additional abnormalities may be present, including heart defects and kidney and spleen malformations. The exact cause of biliary atresia is unknown. (For more information on this disorder, choose "biliary atresia" as your search term in the Rare Disease Database.)
Metabolic liver diseases are a group of disorders in which certain enzymes required to "metabolize" or breakdown various substances in the body (e.g., carbohydrates, proteins, fats) are missing or reduced. Certain of these enzymes are crucial in the production of energy. Absence or deficiency of critical enzymes causes substances to build up in the body potentially damaging various organs. A variety of metabolic diseases are associated with liver dysfunction similar to that found in idiopathic neonatal hepatitis. These disorders include alpha-1-antitrypsin deficiency, cystic fibrosis, fatty acid oxidation disorders, galactosemia, tyrosinemia, Zellweger syndrome, hereditary fructose intolerance and bile acid synthesis defects. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
Neonatal hepatitis may result from a variety of different viral infections that are present at birth (congenital viral infections). Such infections include cytomegalovirus infection, the herpes viruses, enteroviruses, and rubella (measles). Certain nonviral infections can cause neonatal hepatitis including congenital syphilis and toxoplasmosis. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
Certain rare genetic disorders may affect the liver and causes symptoms similar to idiopathic neonatal hepatitis. These disorders include Alagille syndrome, progressive familial intrahepatic cholestasis (PFIC) subtypes, and benign recurrent intrahepatic cholestasis (BRIC). Alagille syndrome is a genetic liver disorder characterized by insufficient passage of bile due to a lower than normal number of bile ducts inside the liver. PFIC is a group of rare genetic disorders that affect the liver characterized by interruption or suppression of the flow of bile from the liver (cholestasis). In PFIC, cholestasis occurs due to defects within the liver (intrahepatic). BRIC is characterized by prolonged recurrent attacks of cholestasis lasting from a few weeks to several months. In most cases, the symptoms of BRIC last for a few weeks or months before improving. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
The key is early recognition of neonatal jaundice – this allows the timely initiation of a diagnostic evaluation, the goals of which are to identify treatable disorders. Therefore any infant jaundiced beyond 14 days of life should have blood test done to determine if the jaundice is due to cholestasis (elevated conjugated bilirubin levels) or is associated with elevated unconjugated bilirubin levels.
Idiopathic neonatal hepatitis is a diagnosis attained by excluding other conditions. Tests may be conducted to rule out viral as well as metabolic diseases and other genetic causes of liver disease. Blood tests may reveal elevated levels of conjugated bilirubin in the blood (hyperbilirubinemia) and decreased levels of certain vitamins because of the failure to the body to proper breakdown food.
The structure of the liver and the surrounding ducts and blood vessels can be examined by ultrasonography. In some cases, a liver biopsy may be necessary. During a biopsy, a needle and syringe are used to remove a small piece of liver tissue. This sample is studied under a microscope. A liver biopsy may be able to rule out other liver disorders such as those that affect the inside of the liver (intrahepatic disorders).
Careful attention to nutritional needs and diet are essential for infants with this disorder. Special supplements (i.e., fat-soluble vitamins), formulas, and/or dietary restrictions may be suggested by the physician. Special infant formulas may be prescribed, for example, malabsorption of long-chain triglycerides may be corrected with formulas that contain medium-chain triglycerides.
There is no specific treatment available for infants with idiopathic neonatal hepatitis. Treatment is directed toward the specific symptoms that are apparent in each individual.
If itching (pruritus) becomes a problem, a drug that has been used to treat itching associated with liver disease is ursodeoxycholic acid.
A surgical choice of last resort for infants who develop end-stage liver disease is a liver transplantation.
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Contact for additional information about idiopathic neonatal hepatitis:
William F. Balistreri, M.D.
Director, Pediatric Liver Care Center
Division of Pediatric Gastroenterology,
Hepatology, and Nutrition
Cincinnati Children's Hospital Medical Center
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Suchy F, Sokol R, Balistreri WF, eds. Liver Disease in Children, 4th Edition. Cambridge University Press, 2014.
Behrman RE, Kliegman RM, Jenson HB. Eds. Nelson Textbook of Pediatrics. 19th Edition. Elsevier Saunders. Philadelphia, PA; 2011.
Patrinos ME, Harrigan R. Idiopathic Neonatal Hepatitis. NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:288.
Balistreri WF, Bezerra JA. Whatever happened to neonatal hepatitis? Clin Liver Dis. 2006;10:27-53.
The Merck Manuals Online Medical Library. Neonatal Cholestasis. February 2012. Available at: http://www.merck.com/mmpe/sec19/ch275/ch275f.html Accessed Dec 30, 2013.
Report last updated: 2014/01/28 00:00:00 GMT+0