Conjugated

Hyperbilirubinaemia

Department of Paediatrics
College of Medicine
University of Ibadan
Synonyms of Conjugated
Hyperbilirubinaemia

 Neonatal cholestasis

 Infantile cholestasis

 Jaundice caused by an elevated

conjugated bilirubin, indicates

hepatobiliary dysfunction
 OBJECTIVES

 Know the differential diagnosis for

neonatal cholestasis.
 Understand how to evaluate the
neonate with conjugated
hyperbilirubinaemia.
 Know the therapeutic management
of neonates with cholestasis.
 Definition: Neonatal Cholestasis

 Prolonged conjugated
hyperbilirubinaemia in the newborn
period
 Conjugated bilirubin >15% of total
bilirubin
 Caused by a group of hepatobiliary
diseases occurring within the first 3
months of life
ETIOLOGIES

 Basic distinction is between:

 Extrahepatic aetiologies
 Intrahepatic aetiologies
Differential Diagnosis:

 Extrahepatic Cholestasis
 Biliary Atresia
 Choledochal cysts
 Spontaneous perforation of the bile duct
 Mucus plug as in cystic fibrosis
Differential diagnosis contd.
 Hepatocellular or Intrahepatic
Cholestasis
 Idiopathic neonatal hepatitis
 Diagnosis based on liver biopsy
findings of giant cell hepatitis
 60-70% resolve without sequelae
 Differential diagnosis contd.
 Infections.
 Viral: TORCH, CMV, HIV, HBV, Coxsakie, Echovirus
 Bacterial: sepsis, UTI secondary to E. coli, Staph
aureus
 Genetic/metabolic - Galactosemia,
hypothyroidism, cystic fibrosis, hypopituitarism
 Toxic/secondary causes: TPN associated
cholestasis
COMMON ETIOLOGIES

 Premature infants
 Sepsis
 TPN-associated
 Idiopathic neonatal hepatitis
 Extrahepatic biliary atresia
 Intrahepatic cholestasis syndromes
 Evaluation
 History
 Pale stool colour:
• Consider cholestatic disease
 Fever, rash in the first trimester of pregnancy:
• Consider TORCH infections
 Haemolysis, jaundice:
• Consider ABO +Rh incompatibility leading to stones
 UTI, Sepsis:
• Consider Neonatal infection
 Diarrhoea, vomiting, poor weight gain on introduction of feeds:
• Consider Galactosaemia, UTI, Sepsis
 Delayed stooling:
• Consider Cystic fibrosis, hypothyroidism
Physical Examination
 Weight :
 Suggestive of Failure To Thrive

 Head circumference:
 Microcephaly suggestive of TORCH
Physical Examination
General appearance:
 Ill-looking:
 Suggestive of infection, metabolic disease
 Well-Looking:
 Suggestive of biliary atresia
 Choroidoretinitis, cataracts:
 Suggestive of TORCH infections and galactosaemia
 Cardiac murmurs:
 Suggestive of Alagille, Congenital form of Biliary atresia
 General appearance (cont’d):
 Ascites, abdominal wall veins, liver and splenic
enlargement:
 Suggestive of Portal hypertension
 Ascites, minimal jaundice, pale stools:
 Spontaneous perforation of the bile duct
 Pale Stool and dark urine:
 Suggestive of Cholestasis
 Skin examination: Bruising, petechiae:
 Dysmorphic features:
 Suggestive of Trisomy 21, 18, 13, Alagille
syndrome
GOALS OF TIMELY EVALUATION

 Diagnose and treat known medical

and/or life-threatening conditions.
 Identify disorders amenable to
surgical therapy within an appropriate
time-frame.
 Avoid surgical intervention in
intrahepatic diseases.
 Laboratory Evaluation
 Total and conjugated bilirubin
 Defines cholestasis
 Liver function tests
 Detects liver cell or bile duct injury
 PT/PTT, albumin
 Detects impairment of synthetic function
 FBC, urine and blood cultures:
 Detects infectious origin of cholestasis
 Viral serologies:
 For TORCH infections, HBsAg, CMV, HIV
 Urinalysis for reducing substances
 Detects galactosaemia
 Thyroid function tests
 Detects hypothyroidism
Imaging Studies
 Ultrasound: Initial study for cholestasis of
unknown etiology and evaluates for
anatomic abnormalities
 Liver Biopsy: For differentiation b/w
extra and intrahepatic processes, disorders
of physiology from anatomy and can
determine need for surgical vs. medical
intervention
 Scintigraphy (HIDA)
 BiliaryAtresia

 Bile duct obstruction due fibrosis and inflammation of bile

ducts of unknown aetiology, though viruses have been
implicated
 Perinatal or “classic”type (70-85%):
Obstruction begins after birth.
Signs/symptoms develop within 2-4 weeks of age.
No associated abnormalities
 Embryonic type (15-30%):
Obstructive process begins in utero.
Cholestatic symptoms present at birth.
Associated with congenital anomalies e.g situs inversus,
polysplenia, asplenia, malrotation, cardiac anomalies
 EXTRAHEPATIC BILIARY
ATRESIA
 Generally acholic stools with onset at about 2
weeks-old
 Average birth weight
 Hepatomegaly with firm to hard consistency
 Increased incidence of polysplenia syndrome
and intra-abdominal vascular anomalies
 Normal uptake on radionucleotide scan with
absent excretion
 Biopsy shows bile duct proliferation, bile plugs,
portal or perilobular fibrosis and edema, and
intact lobular structure
Clinical Features

 Early presentation
 History: Variable degrees of persistent
jaundice, dark urine, light coloured
stools, pruritus
 Usually Well-looking, appear well
nourished
 Hepatomegaly ± splenomegaly
 Imaging Studies
 Ultrasound
Absent gallbladder
Evaluates for other anatomic abnormalities

 Hepatobiliary scintigraphy(HIDA)
High sensitivity
No excretion of radionuclide tracer into biliary system
or bowel in virtually all patients with BA (exceptions
in very early disease)
Failure of excretion may be seen in both BA and
neonatal hepatitis
Sensitivity and Specificity increase with phenobarbitone
administration
 Surgical Management
 Kasai Procedure: Resection of the
obliterated bile duct w/ creation of a
hepatoportoenterostomy
 Timing of procedure predicts the
prognosis
 <56 days-bile flow returned in 80-90% of
cases
 Bile flow established in only 20% after 120
days
 Only 30% with complete drainage. Usually
require a liver transplant within one year
TREATMENT

 Treatment of pruritus
 Bile acid-binders: cholestyramine,
cholestipol
 Ursodeoxycholic acid
 Phenobarbitone as a choleretic
 Naloxone
 Rifampicin
 TREATMENT

 Management of portal hypertension and

its consequences
 Variceal bleeding
 Fluid rescuscitation
 Blood products
 Sclerotherapy
 Balloon tamponade
 Portovenous shunting
 Propanolol
 TREATMENT

 Management of portal hypertension and

its consequences (cont.)
 Ascites
 Sodium restriction
 Diuretics: spironolactone, frusemide
 Albumin
 Paracentesis
 Thrombocytopaenia managed with platelet
infusions when clinically indicated
 Post-operative Management
 Prophylactic Antibiotics for prevention of
cholangitis
 Ursodeoxycholic acid: To enhance bile flow
 No special diet needed unless concern with
poor bile drainage
 Medium Chain Triglycerides
 Fat-soluble vitamins: A, D, E, K
 Short term, high dose steroid therapy
If Kasai Fails?
 Surgical revision of Kasai procedure
 Despite clinical improvement after a Kasai,
70-80% patents will eventually require liver
transplantation

Indications for Liver Transplant:

 Operation not successful in restoring bile

flow initially (~20%)

 Late referrals

 Development of end-stage liver disease

despite bile drainage

 Post-Kasai Complications􀂇
 Early: Ascending Cholangitis(50%) can lead to
ongoing bile duct injury & re-obstruction
 Patients may present with fever, decreased bile
secretion, worsening jaundice, leucocytosis

 Late: Portal Hypertension

 Bleeding oesophageal varices, ascites,
hypoalbuminemia, fat-soluble vitamin deficiency
malabsorbtion of long-chain triglycerides,
encephalopathy
 IDIOPATHIC NEONATAL
HEPATITIS
 Generally normal stools or acholic stools with onset at one
month-old
 Low birth weight
 Normal liver on exam or hepatomegaly with normal to firm
consistency
 Impaired uptake on radionuclide scan with normal excretion
 Biopsy shows intralobular inflammation with focal
hepatocellular necrosis and disruption of the hepatic
architecture. No alteration of the bile ducts. Giant cell
transformation occurs but is non-specific.
 Familial cases (15-20%)
Choledochal cysts
 Choledochal cysts are congenital cystic
dilatations of the extrahepatic biliary tree,
intrahepatic biliary radicles, or both.
 Pathogenesis: Most likely multifactorial. Some
aspects of the disease are consistent with a
congenital aetiology, or a congenital
predisposition to acquire anomaly under the
right conditions
 Clinical Presentation
 Varies with the patient's age.
 In infancy
 Jaundice and passage of acholic stools
 Right quadrant palpable mass
 Hepatomegaly

 Older child
 Intermittent bouts of biliary obstruction or recurrent episodes
of acute pancreatitis
 Jaundice
 Right quadrant palpable mass
 Intermittent attacks of colicky abdominal pain
 Classic clinical triad of abdominal pain, jaundice, and a palpable
right upper quadrant (found in only 10-20% of patients)
Investigations

 LFTs

 Amylase, lipase to R/O Pancreatitis

 Visualisation of cyst

USS, CT, MRI

Types of choledochal cysts
Management
 Surgical excision
Galactosaemia

 Caused by mutation in the galactose-

1-phosphate uridyltransferase (GALT)
gene on chromosome 9.
 Cardinal features: hepatomegaly,
cataracts and mental handicap.
 Presentation
 Feeding difficulty with vomiting and failure to gain
weight with poor growth in the first few weeks of life.
 Lethargy and hypotonia occur.
 Jaundice and hepatomegaly develops.
 There are often associated coagulation defects.
 Sepsis (often with E. coli) can be fatal.
 Cataracts may be apparent even in the early days of
life.
 Ascites may even be apparent in early life.
 Developmental delay may affect speech, language and
general learning.
 Investigations
 Lactose (milk) ingestion results in glucose and
galactose, there will be galactose in the urine.
(Glucose oxidase negative)
 Hyperbilirubinaemia is often unconjugated at
first but becomes conjugated later.
 Real function: Urinary Albumin and aminoacids
 Confirmatory: A quantitative erythrocyte
analysis for galacose 1 phosphate
dehydrogenase activity is required
 Management
 Lactose free milk throughout life. This will
have some immediate benefit but will not
halt all aspects of the disease.

 Antibiotics, intravenous fluids and vitamn

K are often required.

 Special attention for Developmental delay.

Case senario