HEPATOBILIARY DISEASE IN

CHILDREN
Objectives:

By the end of this lecture, the student should be able to:

•Define infant cholestasis
•Classify causes of cholestasis.
•Describe the consequence of cholestasis
•Correlate the abnormalities in LFT with cholestasis.
•Recognize feature of biliary atresia.
•Recognize feature of chronic liver disease.
•Discuss autoimmune hepatitis.
•Discuss viral hepatitis.
•Discuss Wilson’s disease.
•Describe end stage of liver disease.
 Neonatal cholestasis
■ Physiological jaundice in newborns is common but 90% will have
resolved by 2 weeks (3 weeks if preterm).
■ Prolonged (or persistent) neonatal jaundice requires prompt investigation
to distinguish unconjugated (resolves spontaneously) from conjugated
which indicates liver disease.
■ Early diagnosis and management of neonatal liver disease improves
prognosis.
 Definition
 Cholestasis is defined as reduced bile flow and abnormal accumulation
of conjugated bilirubin.
 Neonatal cholestasis is defined as prolonged elevation of serum levels
of conjugated bilirubin beyond the first 14 days of life.
 Cholestasis in a newborn may be due to infectious, genetic, metabolic,
or undefined abnormalities giving rise either to mechanical or
functional impairment of hepatic excretory function.
 Cholestatic jaundice, is an uncommon but potentially serious condition
that indicates hepatobiliary dysfunction.
 Early detection and timely, accurate diagnosis are important for
successful treatment and a favorable prognosis.
 Causes of prolonged (persistent) neonatal jaundice

Unconjugated
 Breastmilk jaundice
 Infection (particularly urinary tract)
 Haemolytic anaemia, e.g. G6PD deficiency
 Hypothyroidism
 High gastrointestinal obstruction
 Crigler–Najjar syndrome
Conjugated (>25 µmol/L)
Bile duct obstruction
• Biliary atresia
• Choledochal cyst
Neonatal hepatitis syndrome
• Congenital infection
• Inborn errors of metabolism
• α 1 -Antitrypsin deficiency
• Galactosaemia
• Tyrosinaemia (type 1)
• Errors of bile acid synthesis
• Progressive familial intrahepatic cholestasis
• Cystic fibrosis
• Intestinal failure-associated liver disease – associated with long-term
parenteral nutrition
Intrahepatic biliary hypoplasia
• Alagille syndrome
 Pathophysiology

■ inflammation of the liver cells or of the cells within the biliary tract.
If bile duct epithelium is the predominant site of disease, cholangitis
may result and lead to progressive sclerosis and narrowing of the
biliary tree, the ultimate state being complete obliteration.

■ hepatic injury may further decrease bile flow and lead to production
of abnormal toxic bile acids.
 Evaluation of the Infant with Cholestasis

History and physical examination Include

– Pregnancy.

– Details of family history.

– Presence of extrahepatic anomalies.

– Stool color.
Clinical Features
&
Complications
of
Liver Disease
Tests to establish the presence and severity of liver disease

■ CBC and reticulocyte count.

■ Fractionated serum bilirubin analysis (total + conjugated)

■ Liver biochemical tests (AST, ALT, alkaline phosphatase, 5′ nucleotidase,

gamma glutamyl transpeptidase)

■ Tests of liver function (prothrombin time, partial thromboplastin time,

coagulation factors, serum albumin level, serum ammonia level, serum
cholesterol level, blood glucose)
 Tests for infection

■ Complete blood count

■ Bacterial and viral cultures of blood, urine, and other sites if indicated.

■ Paracentesis if ascites is present

■ Serologic tests (for hepatitis B, TORCH agents, EBV, others)

 Metabolic studies

■ Urine for reducing substances.

■ Alpha1-antitrypsin level and phenotype.
■ Sweat chloride analysis.
■ Metabolic screen (urine and serum amino acids, urine organic acids).
■ Thyroid hormone, thyroid-stimulating hormone.
■ Serum iron and ferritin.
■ Urine and serum analysis of bile acids and bile acid precursors.
■ Red blood cell galactose-1-phosphate uridyl transferase activity.
 Imaging studies

■ Ultrasonography of the liver and biliary tract.

■ Endoscopic retrograde cholangiopancreatography (ERCP)

■ Magnetic resonance cholangiography.

■ Liver biopsy
Biliary atresia

■ Incidance: 1 in 15 000 live births.

■ There is progressive fibrosis and obliteration of the extrahepatic

and intrahepatic biliary tree.

■ The exact aetiology is unknown.

■ Without intervention, chronic liver failure develops and death

occurs within 2 years.
 Clinical presentation

■ Mild jaundice increases as the disease progresses.

■ Pale stools (the colour may fluctuate but becomes increasingly pale
as the disease progresses).

■ They have normal birth weight followed by faltering growth.

■ Hepatomegaly is often present initially.

■ Splenomegaly develops due to portal hypertension.

Investigations
■ Raised conjugated bilirubin
■ Abnormal liver function test.
■ Fasting abdominal ultrasound may demonstrate a contracted or
absent gallbladder, though it may be normal.
■ Confirmation of the diagnosis is by: cholangiogram (ERCP) or
operative.
■ Liver biopsy: initially demonstrates neonatal hepatitis. Features
of extrahepatic biliary obstruction develop with time.
Endoscopic Retrograde Cholangio-Pancreatography
 Treatment
■ Supportive: pre and post-oprative:
– prevent infection
– Nutrition and fat-soluble vitamin supplementation is essential.

■ Palliative surgery with a Kasai hepatoportoenterostomy (bypasses the

fibrotic ducts and facilitates drainage of bile).
– Early surgery increases the success rate.
– the disease progresses in most children who may develop cholangitis
and cirrhosis with portal hypertension.
■ Liver transplantation is considered.
– Biliary atresia is the single most common indication for liver
transplantation in the paediatric age group.
Kasai Procedure
 Choledochal cysts

■ These are cystic dilatations of the extrahepatic biliary system

which may be detected on antenatal ultrasound scan.
presentation:
– neonatal jaundice
– in older children: abdominal pain, a palpable mass, jaundice, or
cholangitis.
REFERENCES