Intrahepatic disease characterized by conjugated hyperbilirubinemia. More likely to occur in preterm infants or when small for gestational age. Causes may be idiopathic, immune, genetic, metabolic, or infective. Idiopathic neonatal hepatitis is characterized by conjugated hyperbilirubinemia of a prolonged presentation not explained by genetic, metabolic, or infectious causes. Associated with neonatal cholestasis, and differentiated from biliary atresia.

Infectious forms include hepatitis A (HAV), B (HBV), or C (HCV) virus infections, generally transmitted vertically from the mother. Rarely acquired due to blood transfusion or horizontally from medical staff. HAV may be asymptomatic or present with poor feeding, jaundice, fever, vomiting, and hepatomegaly. HBV-infected neonates, even while asymptomatic, are infectious and at risk for developing chronic disease, including cirrhosis and hepatocellular cancer. HCV is less likely to be transmitted vertically by mother or by contaminated blood. There is a slightly greater chance of maternal transmission in human immunodeficiency virus-infected mother. Mostly asymptomatic, infants with acquired HCV may be diagnosed by presence of HCV antibodies. Lengthy membrane rupture and high-risk procedures such as fetal scalp monitoring increase infection risk in newborns exposed to HCV-infected mothers. Some of these children may develop advanced liver disease in later life. Hepatitis D occurs only in the presence of HBV and is rarely vertically transmitted to infant. Hepatitis E is of concern in endemic countries.

Management of HAV is symptomatic, and HAV vaccination is recommended for all infants. Neonates with HBV generally call for monitoring, except in the case of persistent abnormal alanine transaminase, which requires referral to a pediatric hepatitis center. HBV vaccination is recommended for all infants. No vaccine is available yet for hepatitis C.