paeds

• Neonatal liver disease


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


  • Progressive disease in which there is destruction or absence of the extrahepatic biliary tree and intrahepatic biliary ducts
  • Leads to chronic liver failure and death unless surgical intervention is performed
  • Babies have a normal birthweight but fail to thrive as the disease progresses
  • Stool colour may fluctuate, but 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
  • Diagnosis is confirmed at laparotomy by operative cholangiography which fails to outline a normal biliary tree
  • Treatment is surgical bypass of the fibrotic ducts, hepatoportoenterostomy (Kasai procedure)
  • If surgery is performed before age 60 days, 80% of children achieve bile drainage
  • Even when bile drainage is successful, there is frequently progression to cirrhosis and portal hypertension
• Choledochal cysts


  • Cystic dilatations of the extrahepatic biliary system
  • About 25% present in infancy with cholestasis
  • 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
• Neonatal hepatitis syndrome


  • Prolonged neonatal jaundice and hepatic inflammation
  • Causes are often not identified
  • In contrast to biliary atresia, these infants may have intrauterine growth restriction and hepatosplenomegaly at birth
  • Liver biopsy is often non-specific, demonstrating a giant cell hepatitis
• α1-Antitrypsin deficiency


  • Defiency of the protease α1-antitrypsin, associated with liver disease in infancy/childhood and emphysema in adults
  • Inherited as an autosomal recessive disorder
  • Majority of children present with prolonged neonatal jaundice or bleeding due to vitamin K deficiency
  • Diagnosis is confirmed by estimating α1-antitrypsin level and identifying the phenotype
  • Approximately 50% of children have a good prognosis, but the remainder will develop liver disease and may require transplantation
• Galactosaemia


  • Very rare disorder with an incidence of 1 in 40,000
  • Infants develop poor feeding, vomiting, jaundice and hepatomegaly when fed milk
  • Liver failure, cataracts and developmental delay are inevitable if untreated
  • Diagnosis is made by measuring the enzyme galactose-1-phosphate-uridyl transferase in red cells
  • A galactose-free diet prevents progression of liver disease, but ovarian failure and learning difficulties may occur later
• Inborn errors of bile acid synthesis

  • Patients presenting with neonatal cholestasis and normal GGT should be screened
  • Diagnosis is confirmed by mass spectrometry of urine for bile acids
  • Specific treatment is with ursodeoxycholic acid
• Progressive familial intrahepatic cholestasis (PFIC)

  • Heterogeneous group of cholestatic disorders of bile transporter defects caused by recessive mutations
  • Children present with jaundice, intense pruritus, diarrhoea with failure to thrive, rickets
  • In two forms, the GGT is low
  • Prognosis is variable, some children require liver transplantation
• Alagille syndrome


  • Rare autosomal dominant condition with widely varying penetrance
  • Infants may have characteristic triangular facies, skeletal abnormalities, congenital heart disease, renal tubular disorders, eye defects and intrahepatic biliary hypoplasia with severe pruritus and failure to thrive
  • Prognosis is variable, with 50% of children surviving into adult life without liver transplantation
• Viral hepatitis


  • Clinical features include nausea, vomiting, abdominal pain, lethargy and jaundice
  • 30-50% of children do not develop jaundice
  • A large tender liver is common and 30% will have splenomegaly
  • Liver transaminases are usually markedly elevated, but coagulation is usually normal
• Hepatitis A


  • Caused by an RNA virus spread by faecal-oral transmission
  • Incidence has fallen as socioeconomic conditions have improved
  • Many adults are not immune, vaccination is required for travellers to endemic areas
  • Disease may be asymptomatic, but majority of children have a mild illness and recover within 2-4 weeks
  • Some may develop prolonged cholestatic hepatitis or fulminant hepatitis
• Intrahepatic biliary hypoplasia


  Occurs in Down syndrome, also a non-syndromic form
• Clinical features of viral hepatitis

  • Nausea, vomiting, abdominal pain, lethargy, jaundice
  • 30-50% of children do not develop jaundice
  • Large tender liver is common
  • 30% will have splenomegaly
  • Liver transaminases are usually markedly elevated
  • Coagulation is usually normal
• Hepatitis A virus (HAV)

  RNA virus spread by faecal-oral transmission
• Incidence of hepatitis A in childhood has fallen as socioeconomic conditions have improved
• Hepatitis A disease


  • May be asymptomatic, but majority have mild illness and recover within 2-4 weeks
  • Some may develop prolonged cholestatic hepatitis or fulminant hepatitis
  • Chronic liver disease does not occur
• Diagnosis of hepatitis A

  Confirmed by detecting IgM antibody to the virus
• There is no treatment for hepatitis A and no evidence that bed rest or change of diet is effective
• Close contacts should be given prophylaxis with human normal immunoglobulin (HNIG) or vaccinated within 2 weeks of onset
• Hepatitis B virus (HBV)


  DNA virus, important cause of acute and chronic liver disease worldwide
• Modes of HBV transmission

  • Perinatal transmission from carrier mothers
  • Transfusion of infected blood or blood products
  • Needlestick injuries with infected blood
  • Renal dialysis
  • Horizontal spread within families
  • Sexually among adults
• Infants who contract HBV perinatally

  Asymptomatic, but at least 90% become chronic carriers
• Older children who contract HBV

  • May be asymptomatic or have classical features of acute hepatitis
  • Majority will resolve spontaneously, but 1-2% develop fulminant hepatic failure, 5-10% become chronic carriers
• Diagnosis of acute HBV infection

  • IgM antibodies to the core antigen (anti-HBc) are positive
  • Positivity to hepatitis B surface antigen (HBsAg) denotes ongoing infectivity
• Chronic hepatitis B


  • Infants infected by vertical transmission from mothers usually become asymptomatic carriers
  • 30-50% of carrier children will develop chronic HBV liver disease, which may progress to cirrhosis in 10%
  • There is a long-term risk of hepatocellular carcinoma
• Treatment for chronic hepatitis B


  • Interferon treatment successful in 50% of children infected horizontally and 30% infected perinatally
  • Oral antiviral therapy like lamivudine effective in 23% but limited by resistance
  • Newer drugs like adefovir or long-acting interferon may be more effective
• Prevention of perinatal HBV transmission

  1. All pregnant women screened for HBsAg

  2. Babies of HBsAg-positive mothers given hepatitis B vaccine course, with hepatitis B immunoglobulin if mother is HBeAg-positive

  3. Antibody response checked in high-risk infants, further vaccination if needed

  4. Other family members also vaccinated
• Effective neonatal vaccination reduces incidence of HBV-related cancer
• Hepatitis C virus (HCV)

  RNA virus, responsible for 90% of post-transfusion hepatitis until donor blood screening introduced in 1991
• Children previously at risk of HCV

  Those who received unscreened blood or blood products, in particular those with haemoglobinopathies or haemophilia
• Vertical transmission of HCV

  Occurs in 6% from infected mothers, twice as common if co-infected with HIV, now commonest cause of HCV transmission in children
• HCV seldom causes acute infection, but majority become chronic carriers
• Lifetime risk with chronic HCV

  20-25% progression to cirrhosis or hepatocellular carcinoma
• Treatment for chronic HCV

  Combination of pegylated interferon and ribavirin, success depends on virus genotype (up to 90% effective for genotypes 2/3)
• Treatment not undertaken before 4 years of age as HCV may resolve spontaneously following vertical transmission
• Hepatitis D virus (HDV)


  Defective RNA virus that depends on hepatitis B virus for replication, occurs as co-infection or superinfection causing acute exacerbation of chronic hepatitis B
• Chronic HDV infection


  Cirrhosis develops in 50-70% of cases
• Hepatitis E virus


  RNA virus transmitted enterally, usually by contaminated water, epidemics occur in some developing countries
• Non-A to G hepatitis

  Clinical presentation similar to hepatitis A, when viral aetiology is suspected but not identified
• Epstein-Barr virus (EBV) infection

  Children are usually asymptomatic, 40% have hepatitis that may become fulminant, less than 5% are jaundiced