Liver & intrahepatic bile ducts
Noninfectious hepatitis
Neonatal hepatitis
Author: Anthony W.H. Chan, M.B.Ch.B.
Editorial Board Member: Kimberley J. Evason, M.D., Ph.D.
Deputy Editor-in-Chief: Aaron R. Huber, D.O.
Last author update: 19 September 2024
Last staff update: 19 September 2024
Copyright: 2002-2025, PathologyOutlines.com, Inc.
PubMed Search: Neonatal hepatitis
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Negative stains | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Chan AWH. Neonatal hepatitis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/liverneonatalhep.html. Accessed April 2nd, 2025.
Definition / general
- Neonatal hepatitis is a heterogeneous group of diseases caused by various underlying causes but sharing similar morphological features, including a hepatitic histological pattern and notable giant cell transformation (Hum Pathol 2021;112:102)
Essential features
- There are various causes leading to neonatal hepatitis
- Idiopathic neonatal hepatitis is a diagnosis by exclusion
- Despite different causes, similar morphological features are found, including a hepatitic histological pattern (predominant lobular necroinflammatory activity and notable giant cell transformation)
Terminology
- Also known as neonatal giant cell hepatitis because of frequent giant cell transformation
ICD coding
Epidemiology
- Neonatal cholestasis happens in about 1 in 2,500 term infants (J Pediatr Gastroenterol Nutr 2017;64:154)
- Idiopathic neonatal hepatitis, infection, metabolic diseases and alpha-1 antitrypsin deficiency account for 26.0%, 11.5%, 4.4% and 4.1% of neonatal conjugated hyperbilirubinemia, respectively (BMC Pediatr 2015;15:192)
Etiology
- Idiopathic neonatal hepatitis
- Infection: virus (cytomegalovirus, rubella, hepatitis B, hepatitis C, herpes simplex virus, herpes zoster virus, echovirus, coxsackie virus), Toxoplasma, Treponema pallidum (congenital syphilis) and others
- Metabolic: galactosemia, tyrosinemia, fructosemia, neonatal hemochromatosis, hypopituitarism, hypothyroidism
- Alpha-1 antitrypsin deficiency
- Progressive familial intrahepatic cholestasis, type 2
- Bile acid synthetic defects (BASDs)
- Alagille syndrome: can present with different patterns, including neonatal hepatitis
- References: BMC Pediatr 2015;15:192, Hum Pathol 2021;112:102
Clinical features
- Prolonged jaundice beyond 2 weeks of age
- Other clinical features depend on the underlying etiology
Diagnosis
- Histology is crucial to establishing the diagnosis, whereas clinical and laboratory features help look for the underlying etiology (J Pediatr Gastroenterol Nutr 2017;64:154)
Laboratory
- Elevated conjugated bilirubin
- Elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
- Normal or low gamma glutamyl transferase (GGT)
- Microbiological tests, metabolic screening, thyroid function test and serum bile acids for the underlying etiology
- Reference: Hum Pathol 2021;112:102, J Pediatr Gastroenterol Nutr 2017;64:154
Radiology description
- Liver ultrasound is important to exclude biliary obstruction other than biliary atresia
- Hepatobiliary scintigraphy may not add much to a thorough clinical examination in order to confirm or rule out biliary atresia
- Surgical cholangiography, endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous cholangiography but not magnetic resonance cholangiopancreatography (MRCP) are useful for excluding biliary atresia and neonatal sclerosing cholangitis
- MRCP is unreliable in infants younger than 3 months because the normal biliary tree is often not clearly visualized
- Reference: Dig Liver Dis 2022;54:40
Case reports
- Newborn boy with idiopathic neonatal hepatitis presented with acute hepatic failure (J Perinatol 2002;22:249)
- Newborn girl with neonatal hepatitis associated with gestational alloimmune liver disease - neonatal hemochromatosis (BMJ Case Rep 2024;17:e257950)
- 42 day old boy with neonatal hepatitis and infarction associated with congenital syphilis (Arch Argent Pediatr 2023;121:e202202719)
- 7 week old girl with fatal spontaneous subdural bleeding due to neonatal hepatitis (Forensic Sci Med Pathol 2011;7:294)
- 3 month old boy with neonatal hepatitis associated with congenital combined pituitary hormone deficiency (Clin Pediatr Endocrinol 2017;26:251)
- 4 month old boy with neonatal hepatitis associated with copper toxicosis (J Clin Exp Hepatol 2022;12:719)
Treatment
- Specific treatment if the exact etiology is known
- Supportive and preventive care and management of complications (malnutrition and fat soluble vitamin deficiencies, pruritus, xanthoma formation and progressive fibrosis)
- Reference: Curr Gastroenterol Rep 2023;25:344
Microscopic (histologic) description
- Lobular changes are more signficant than portal changes
- Lobular changes: prominent giant cell transformation (hepatocytes containing 4 - 10 nuclei), variable lobular necroinflammatory activity, canalicular with or without hepatocellular cholestasis
- Portal tract changes: variable portal mononuclear inflammatory infiltrate
- Extramedullary hematopoiesis
- Other changes depend on the underlying etiology
- Reference: Hum Pathol 2021;112:102
Microscopic (histologic) images
Contributed by Anthony W.H. Chan, M.B.Ch.B.
Extensive hydropic degeneration
Giant cell transformation
Lobular necroinflammatory activity
Extramedullary hematopoiesis
Cholestasis
Negative stains
Sample pathology report
- Liver, biopsy:
- Neonatal giant cell hepatitic pattern (see comment)
- Comment: In the presence of prominent lobular necroinflammatory activity and frequent giant cell formation, the overall features are those of neonatal hepatitis. The current biopsy does not reveal viral inclusion, steatosis or aberrant cytoplasmic deposit / inclusion. Correlation with clinical features, laboratory tests or genetic tests are required to establish the underlying cause. Idiopathic neonatal hepatitis is a diagnosis of exclusion.
Differential diagnosis
- Extrahepatic biliary atresia:
- Diagnostic accuracy of different methods distinguishing extrahepatic biliary atresia from idiopathic neonatal hepatitis: liver biopsy (97.1%), hepatobiliary scintigraphy (66.7%), ultrasound (65.2%) (Clin Imaging 2009;33:439)
- Ductular reaction, ductular cholestasis and portal fibrosis are essential discriminatory histological features suggestive of extrahepatic biliary atresia (Eur J Gastroenterol Hepatol 2014;26:1300, J Hepatol 2014;61:116)
- Presence of CD56+ bile ducts and ductules favor extrahepatic biliary atresia (Am J Surg Pathol 2003;27:1454)
- Paucity of intrahepatic bile ducts:
- Absent interlobular bile ducts in > 50% of portal tracts (Hum Pathol 2021;112:102)
Board review style question #1
A liver biopsy is taken from a 1 month old boy presenting with conjugated jaundice and deranged liver function. Hepatic scintigraphy and cholangiography are equivocal. Which of the following features favors the diagnosis of neonatal hepatitis?
- Absent interlobular bile ducts in > 50% of portal tracts
- Cholestasis
- Ductular reaction
- Prominent lobular necroinflammatory activity
Board review style answer #1
D. Prominent lobular necroinflammatory activity and significant giant cell transformation are typical for neonatal hepatitis. Answer A is incorrect because absent interlobular bile ducts in > 50% of portal tracts is diagnostic of paucity of intrahepatic bile ducts. Answer B is incorrect because cholestasis is nonspecific and can be present in any cause of neonatal cholestasis. Answer C is incorrect because ductular reaction is much more obvious in extrahepatic biliary atresia.
Comment Here
Reference: Neonatal hepatitis
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Reference: Neonatal hepatitis
Board review style question #2
Which of the following radiological investigations helps exclude biliary atresia in patients with suspected neonatal hepatitis?
- Endoscopic retrograde cholangiopancreatography (ERCP)
- Hepatic ultrasound
- Hepatobiliary scintigraphy
- Magnetic resonance cholangiopancreatography (MRCP)
Board review style answer #2
A. Endoscopic retrograde cholangiopancreatography (ERCP). Cholangiograms, including surgical cholangiography, ERCP and percutaneous cholangiography, are valuable tools in diagnosing biliary atresia. They help visualize bile duct anatomy and assess any blockages or malformations, aiding in differentiating biliary atresia from other causes of neonatal cholestasis. Answer B is incorrect because liver ultrasound is important to exclude biliary obstruction other than biliary atresia. Answer C is incorrect because hepatobiliary scintigraphy may not add much to a thorough clinical examination in order to confirm or rule out biliary atresia. Answer D is incorrect because MRCP is unreliable in infants younger than 3 months since the normal biliary tree is often not clearly visualized.
Comment Here
Reference: Neonatal hepatitis
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Reference: Neonatal hepatitis
