Liver disorders

Features of liver disorders in children are:

• 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.

Figure 20.1 Clinical features of liver disease. In addition, these children may have growth failure and developmental delay.

• 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.

In prolonged (persistent) neonatal jaundice, check if it is conjugated hyperbilirubinaemia, as this is due to liver disease.

Bile duct obstruction

Biliary atresia (see Case History 20.1)

This occurs in 1 in 14 000 live births. It is a progressive disease, in which there is destruction or absence of the extrahepatic biliary tree and intrahepatic biliary ducts. This leads to chronic liver failure and death unless surgical intervention is performed. Babies with biliary atresia have a normal birthweight but fail to thrive as the disease progresses. They are usually mildly jaundiced and, following passage of meconium, their stools are pale and their urine dark. Although stool colour may fluctuate, pale stools is an important abnormality and warrants investigation, even in the absence of clinical jaundice. Hepatomegaly is often present and splenomegaly will develop secondary to portal hypertension.

Standard liver function tests are of little value in the differential diagnosis. A fasting abdominal ultrasound may demonstrate a contracted or absent gallbladder, though it may be normal. A radioisotope scan with TIBIDA (iminodiacetic acid derivatives) shows good uptake by the liver, but no excretion into the bowel. Liver biopsy demonstrates features of extrahepatic biliary obstruction, although features may overlap with those of neonatal hepatitis, especially if carried out at an early stage of the disease. The diagnosis is confirmed at laparotomy by operative cholangiography which fails to outline a normal biliary tree.

Treatment consists of surgical bypass of the fibrotic ducts, hepatoportoenterostomy (Kasai procedure), in which a loop of jejunum is anastomosed to the cut surface of the porta hepatis, facilitating drainage of bile from any remaining patent ductules. If surgery is performed before the age of 60 days, 80% of children achieve bile drainage. The success rate diminishes with increasing age – hence the need for early diagnosis and treatment. Postoperative complications include cholangitis and malabsorption of fats and fat-soluble vitamins. Even when bile drainage is successful, there is frequently progression to cirrhosis and portal hypertension. If the operation is unsuccessful, liver transplantation has to be considered. Biliary atresia is the single most common indication for liver transplantation in the paediatric age group.

Choledochal cysts

These are cystic dilatations of the extrahepatic biliary system. About 25% present in infancy with cholestasis. In the older age group, choledochal cysts present with abdominal pain, a palpable mass and jaundice or cholangitis. The diagnosis is established by ultrasound or radionuclide scanning. Treatment is by surgical excision of the cyst with the formation of a Roux-en-Y anastomosis to the biliary duct. Future complications include cholangitis and a 2% risk of malignancy, which may develop in any part of the biliary tree.

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.

Figure 20.6 Liver biopsy in neonatal hepatitis showing inflammatory infiltrate throughout the liver, and giant cell and rosette formation of liver cells.

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).