• Prolonged (persistent) neonatal jaundice is the most common presentation of liver disease in the neonatal period.

• The earlier in life biliary atresia is diagnosed and treated surgically, the better the prognosis.

• Transmission of hepatitis B surface antigen-positive mothers is prevented by immunising their babies.

• Chronic liver disease (Fig. 20.1), cirrhosis and portal hypertension are uncommon and should be managed by, or in conjunction with tertiary or national centres.

• Liver transplantation is an effective therapy for acute or chronic liver failure, with a >80% 5-year survival rate; it is only performed at national centres.

Neonatal liver disease

Many newborn infants become clinically jaundiced. About 5–10% are still jaundiced at >2 weeks of age (3 weeks if preterm), when it is called ‘prolonged (or persistent) neonatal jaundice’. This is usually an unconjugated hyperbilirubinaemia, which resolves spontaneously (Box 20.1). Prolonged neonatal jaundice caused by liver disease is characterised by a raised conjugated bilirubin (>20 µmol/L) and is usually accompanied by:

There is an urgency to diagnose liver disease as early as possible in the neonatal period, because early diagnosis and management improves prognosis.

Neonatal hepatitis syndrome

In neonatal hepatitis syndrome, there is prolonged neonatal jaundice and hepatic inflammation. Its causes are listed in Box 20.1, but often no specific cause is identified. In contrast to biliary atresia, these infants may have intrauterine growth restriction and hepatosplenomegaly at birth. Liver biopsy (Fig. 20.6) is often non-specific, demonstrating a giant cell hepatitis.

α₁-Antitrypsin deficiency

Deficiency of the protease α₁-antitrypsin is associated with liver disease in infancy and childhood and emphysema in adults. It is inherited as an autosomal recessive disorder with an incidence of 1 in 2000–4000 in the UK. There are many phenotypes of the protease inhibitor (Pi) which are coded on chromosome 14. Liver disease is primarily associated with the phenotype PiZZ.

Case History

20.1 Biliary atresia

A term infant was given oral vitamin K shortly after birth. He was breast-fed. He became mildly jaundiced on the third day of life. At 5 weeks of age, he presented with poor feeding and vomiting and a history of bruising on his forehead and shoulders. His urine had become dark and stools intermittently pale. He was pale, jaundiced, had several bruises and hepatomegaly. Investigations showed:

• Hb 8.8 g/L

• Platelets 465 × 10⁹/L

• Prothrombin time – 28 s (normal range 10–13 s)

• Serum bilirubin 178 micromol/L – 140 micromol/L conjugated.

The investigation of conjugated hyperbilirubinaemia is shown in Figure 20.2. The TIBIDA radionuclide scan showed no excretion at 24 h (Fig. 20.3) and a liver biopsy suggested biliary atresia (Fig. 20.4). A hepatoportoenterostomy was performed at 6 weeks of age (Fig. 20.5).

In persistent neonatal jaundice, early diagnosis of biliary atresia improves the prognosis.

 In persistent jaundice, always look to see if the stools are pale – suggests bile duct obstruction.

The majority of children who present with α₁-antitrysin deficiency will either have prolonged neonatal jaundice or, less commonly, bleeding due to vitamin K deficiency (haemorrhagic disease of the newborn). Hepatomegaly is present. Splenomegaly develops with cirrhosis and portal hypertension. The diagnosis is confirmed by estimating the level of α₁-antitrypsin in the plasma and identifying the phenotype. Approximately 50% of children have a good prognosis, but the remainder will develop liver disease and may require transplantation. Pulmonary disease is not significant in childhood, but is likely to develop in adult life. Advice to avoid smoking (both active and passive) should be given. The disorder can be diagnosed antenatally.

Galactosaemia

This very rare disorder has an incidence of 1 in 40 000. The infants develop poor feeding, vomiting, jaundice and hepatomegaly when fed milk. Liver failure, cataracts and developmental delay are inevitable if galactosaemia is untreated. A rapidly fatal course with shock, haemorrhage and disseminated intravascular coagulation, often due to Gram-negative sepsis, may occur.

The condition can be screened for, in prolonged (persistent) jaundice, by detecting galactose, a reducing substance, in the urine. The diagnosis is made by measuring the enzyme galactose-1-phosphate-uridyl transferase in red cells. A recent blood transfusion may mask the diagnosis. A galactose-free diet prevents progression of liver disease, but ovarian failure and learning difficulties may occur later.

Other causes

Neonatal hepatitis may occur following prolonged parenteral nutrition. Rare causes include tyrosinaemia type 1, cystic fibrosis, lipid and glycogen storage disorders, peroxisomal disorders, inborn errors of bile acid synthesis and progressive familial intrahepatic cholestasis (PFIC).

Inborn errors of bile acid synthesis

Patients presenting with neonatal cholestasis of infancy and normal levels of gamma glutamyl transferase (GGT) should be screened for elevated cholenoic bile acids in urine. Diagnosis is confirmed by mass spectrometry of urine for bile acids. Specific treatment is with ursodeoxycholic acid.

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