Neonatal hepatitis syndrome is a neonatal disease caused by various factors, with the main pathological feature being the formation of nonspecific multinucleated giant cells. It primarily manifests as jaundice and generally has a favorable prognosis. Most cases are caused by infections during or after childbirth, while a few are related to congenital metabolic defects. In some cases, the cause of the disease remains unknown.

bubble_chart Etiology

Disease cause

Neonatal hepatitis syndrome includes hepatitis caused by hepatitis B virus, cytomegalovirus, herpes simplex virus, coxsackievirus, and rubella virus, among others. It can also be caused by ECHO virus, EB virus, Toxoplasma gondii, Listeria, or various bacteria. These pathogens can infect the fetus through the placenta or during or after delivery. A small number of cases are related to congenital metabolic defects. In some cases, the disease cause is unknown.

Pathological changes

Although the disease causes are numerous, the main pathological changes are nonspecific multinucleated giant cell formation. Bile stasis, inflammatory cell infiltration in the hepatic interstitium and portal areas, the extent of which correlates with the severity of the condition. In mild cases, the hepatic lobule structure remains normal, while in severe cases, it may become disordered. Hepatocytes may exhibit focal or patchy necrosis, with Kupffer cell and small bile duct proliferation. In chronic cases, periportal fibrosis may occur. The affected cells in cytomegalic inclusion disease are characterized by owl's eye-like intranuclear inclusions.

bubble_chart Clinical Manifestations

The main manifestation is jaundice. Patients often seek medical attention due to persistent physiological jaundice or its recurrence after fading. Other symptoms such as low-grade fever, vomiting, abdominal distension, and fullness may also occur. Physical examination reveals hepatosplenomegaly, dark urine, and stools that change from yellow to light yellow or even white. In most cases, jaundice gradually subsides within 3 to 4 months, but complications such as dry eye disease, hypocalcemic spasms, bleeding, and diarrhea may occur. A small number of severe cases with prolonged disease course may develop cirrhosis and liver failure. Laboratory tests show that total bilirubin is generally below 171 μmol/L (10 mg/dl), with both conjugated and unconjugated bilirubin elevated, predominantly the former. Alanine aminotransferase (ALT) may be elevated or normal. Alpha-fetoprotein (AFP), which should become negative after one month in newborns, may remain elevated in patients, indicating increased destruction and regeneration of hepatocytes. AFP typically peaks about one week after the ALT peak. Serum alkaline phosphatase levels are normal.

The diagnosis of neonatal hepatitis syndrome is relatively difficult. Among infants born to mothers who are positive for hepatitis B surface antigen (HBsAg), 20–50% become HBsAg carriers within the first six months of life, though most remain asymptomatic. The likelihood of mother-to-child transmission of hepatitis B virus is much higher during delivery through the birth canal than during intrauterine transmission. In a study of 80 infants with the syndrome conducted by the Second Affiliated Hospital of China Medical University, viral isolation from urine and partial serum IgM antibody testing confirmed 12 cases as cytomegalovirus hepatitis. At the Xinjiang Autonomous Region Hospital, half of the 16 cases of neonatal hepatitis showed cytomegalovirus inclusion bodies in urinary exfoliated cells. Jaundice caused by neonatal sepsis may yield positive blood cultures. Additionally, there are cases of neonatal jaundice disease with unknown causes.

This condition is sometimes difficult to differentiate from congenital biliary atresia in newborns. However, misdiagnosing neonatal hepatitis as biliary atresia and proceeding with surgery can worsen the condition. The differential diagnosis between these two diseases is discussed in the section on biliary atresia below.

bubble_chart Treatment Measures

Therapeutic measures

Chinese medicinals Virgate Wormwood and Sanhuang Decoction (see the comprehensive treatment for neonatal jaundice above) can be taken long-term. For severe cases, injections can be used once or twice daily. Short-term use of adrenal corticosteroids may help alleviate jaundice. Additionally, liver-protective treatment can be administered by referring to the principles of integrated traditional Chinese and Western medicine for acute hepatitis A.

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The prognosis is relatively good, with 60-70% of cases being curable. The progression to cirrhosis or death is less common. According to a 10-year observation by Xinhua Hospital affiliated with Shanghai Second Medical College (including cases of biliary atresia), the mortality rate was 13%. Recent reports indicate that the hepatitis B vaccine can effectively prevent mother-to-child transmission.