Chronic Liver Diseases in Pediatrics

To learn about chronic liver diseases in pediatrics, we need to understand the two types of hyperbilirubinemia.

Unconjugated Hyperbilirubinemia

It is caused by an increase in the indirect fraction of the bilirubin. There are two pathophysiologies of this they are:

• Increased production: this can be due to Hemolytic disorders or Ineffective Erythropoiesis.
• Decreased Conjugation: Decreased conjugation can be due to 
  • Gilbert syndrome
    • Mild deficiency of UDPGT 
    • Increase during stress, fasting, fatigue
  • Criggler Najjar syndrome
    • Type I: severe, complete absence of UDPGT
    • Type II: Milder illness with decreased UDPGT

Conjugated Hyperbilirubinemia

Conjugated or direct bilirubin is >2 mg/dl or >20% of total bilirubin.

• Dubin Johnson Syndrome
  • Impaired excretion of conjugated bilirubin due to mutation in canalicular multidrug resistance protein 2 (MRP-2)
  • Dark pigmentation of the liver.
• Rotor Syndrome
  • Decreased hepatic uptake, storage & biliary excretion of bilirubin.
• PFIC (Progressive Familial Intrahepatic cholestasis)
  • Severe cholestatic jaundice beginning in childhood
  • 3 types: GGT enzyme level elevated only in PFIC type 3
•  Biliary Atresia (Extra Hepatic Biliary Atresia/EHBA) 
  • Screening test: HIDA Scan (hepatic scintigraphy)
  • Surgery: Kasai procedure. It has a good outcome if done <8 weeks of age.
  • A very close Differential of EHBA is neonatal hepatitis.

Two of the most important disorders of Conjugated hyperbilirubinemia are neonatal hepatitis and Biliary Atresia. These are explained in a short and concise way. 

Portal Hypertension in Children      

Portal hypertension in pediatrics is defined as the elevation of portal pressure >10-12mm Hg. It happens due to obstruction to portal blood flow, anywhere along the course of portal venous system.

Causes of Portal Hypertension in Children

1. Prehepatic (Presinusoidal)

• Due to portal vein obstruction from any cause.
• Portal vein thrombosis is the MC cause of extrahepatic portal hypertension
• Neonates: Omphalitis, UVC, dehydration, sepsis
• Older children:  Appendicitis, peritonitis, inflammatory bowel disease, Hypercoagulable state.
• The most common cause of portal hypertension in children is EHPVO (Extrahepatic portal venous obstruction)

2. Intrahepatic (Sinusoidal)

• Important causes of Cirrhosis in children:

• MC intrahepatic cause of portal hypertension in children: Cirrhosis
• Biliary atresia
• Chronic viral hepatitis
• Autoimmune hepatitis
• Metabolic liver disease
• In some children, non-cirrhotic portal fibrosis (NCPF) 

3. Post-hepatic (Post-sinusoidal) 

• Budd Chiari syndrome 
• Veno-occlusive disease 

Clinical features of portal hypertension in Children

• Bleeding is the most common presentation of portal hypertension in children.
• Splenomegaly: enlarged spleen
• Ascites: fluid in the abdominal cailty
• Growth failure
• Cyanosis
• Clubbing
• Dyspnea

Lets discuss a few liver disorders in pediatrics in detail.

Budd Chiari Syndrome

Budd Chiari syndrome is due to obstruction to Hepatic veins anywhere between the efferent hepatic veins to the entry of IVC into the right atrium. This obstruction can be Due to 

• Hypercoagulable structure
• Malignancy
• Inflammatory bowel disease 
• Behcet syndrome

Veno-Occlusive disease 

Veno occlusive disease are the most common cause of hepatic venous obstruction in children. Occlusion of centrilobular venules or sub-lobular hepatic veins is seen in this disease. It occurs most frequently in BM transplant recipients after total body irradiation.

Viral Hepatitis in Children is covered extensively here. This is a very important topic for NEET PG / FMGE exams.

Wilson Disease

• Autosomal recessive
• ATP 7B gene mutation (Chr 13q 14)
• Decreased biliary copper excretion & accumulation of copper in hepatocytes.

Clinical features of Wilson Disease

• Hepatic: Hepatomegaly, Hepatitis, liver failure, portal hypertension, ascites
• Hematologic: hemolytic anemia
• CNS: Tremors, dysarthria, dystonia, chorea.
• Eye: KF ring (Kayser Fleischer ring) & Sunflower cataract.
• Renal: Fanconi syndrome, renal failure

Investigation of Wilson Disease

• Decreased Serum ceruloplasmin level.
• Serum free copper level may be elevated
• Urinary copper excretion increased
• Hepatic copper content > 250 microgram/gm of dry liver weight
• KF ring: On slit lamp exam of eye.

Treatment of Wilson Disease

• Restrict dietary copper intake
• Avoid liver, shellfish, nuts, chocolates
• Use Copper chelating agents like 
  • d- penicillamine
  • Zinc
  • Trientine      

Reye Syndrome

• Acute metabolic disorder resulting in generalized mitochondrial dysfunction due to inhibition of fatty acid oxidation.
• Also known as “Jamshedpur Fever”.
• Fatty liver & encephalopathy seen 
  • Cerebral edema
  • Hepatic encephalopathy

Precipitation factors of Reye syndrome 

• Drugs (NSAIDs)
• toxins
• IEM
• viruses e.g., Coxsackie V, Influenza V, Adeno V, Varicella V (not by RSV).

Clinical features of Reye syndrome

• Features of hepatic dysfunction- Hypoglycemia, Bleeding (prolonged patient), But Jaundice is rare.
• Seizures & encephalopathy seen in > 80%

Prognosis of Reye’s Syndrome

Poor (Mortality 25-70% cases) 

Frequently Asked Questions:

Q: What is the most common indication of liver transplant in children?

Answer: Biliary atresia.

Q. In a neonate on phototherapy, bilirubin is converted into? (AIIMS June 2020)

A. Biliverdin

B. Lumirubin

C. Urobilin

D. Stercobilin

Answer: B. Lumirubin

Q: A 3-year-old male child with a fever for 5 days was given some medication (Aspirin) and developed anorexia, vomiting, altered sensorium, and Seizures. O/E: No jaundice but hepatomegaly seen. On Investigation: Hypoglycemia, prolonged PT. What is the Diagnosis in this child?

Answer: Reye syndrome

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