Liver Conditions

One of the main symptoms of paediatric liver conditions is jaundice. Whilst neonatal jaundice is a common finding, jaundice in the first 24 hours is always pathological.

– This may be due to haemolytic disorders, infection, or metabolic liver disorders like Crigler-Najjar syndrome.

– The problem with this is that is can lead to raised levels of unconjugated bilirubin in the blood.

– As this is fat soluble, it can cross the blood brain barrier is very neurotoxic and cause irreversible neurological symptoms. 

Biliary Atresia

This is a condition where there is progressive fibrosis and obliteration of the biliary tree, which impedes the outflow of bile.

– Consequently, the bile starts to back-up and resembles a cholestatic picture.

– As the hepatocytes still function and can conjugate the bilirubin, this leads to a conjugated bilirubinaemia (so less risk of kernicterus)

– Bile is very hepatotoxic and leads to progressive degradation of the liver.

– If left untreated, this will progress onto early onset liver cirrhosis and portal hypertension

Symptoms:

– Mild jaundice in the first few weeks of life

– Cholestasis signs –> pale stools, dark urine

– Normal birthweight which is then followed by poor levels of growth and appetite

– Hepatomegaly with later splenomegaly (due to portal hypertension)

– If left untreated signs of liver cirrhosis

Tests:

– Blood test shows high ALP, ALT, and high levels of conjugated bilirubin

– Ultrasound shows biliary tract distension with a contracted or absent gallbladder

– ECRP –> fails to outline a normal biliary tree

Management:

– 1st line is Kasai procedure – This is a Hepatoportoenterostomy (loop of jejunum anastomosed to cut surface of porta hepatis)

– If unsuccessful, liver transplant maybe required

Genetic Liver Diseases

This is a group of autosomal recessive disorders which lead to errors in bilirubin conjugation, uptake, or excretion by the liver.

– The ones which lead to an Unconjugated hyperbilirubinaemia are much more serious as this can cross the BBB to cause neurological problems.

Gilbert’s Syndrome

This is a syndrome which is due to a mild deficiency of UDP-glucoronyltransferase (enzyme that conjugates Bilirubin)

Gene:

UGT1A1 

Inheritance:

Autosomal Recessive

Symptoms:

– Jaundice in times of stress e.g illness, exercise or fasting

– It is a mild condition

-Most people are asymptomatic except in times of stress

Blood Test:

Raised unconjugated bilirubin

Management:

Usually does not require treatment

Crigler-Najjar

This is a syndrome where there is an absolute deficiency of UDP-glucoronyltransferase

– Type 1 is absolute deficiency

– Type 2 is severe but not absolute deficiency

Gene:

UGT1A1

Inheritance:

Autosomal Recessive

Symptoms:

– This gives a very severe neonatal jaundice

– Very important to treat as it can lead to kernicterus

-Type 1 has a high child mortality

Blood Test:

Raised unconjugated bilirubin 

Management:

Treated with phototherapy and liver transplant

Dubin-Johnson Syndrome

This is a syndrome where where this is defective hepatic excretion of bilirubin

– It is more common in the Iranian Jewish population

Gene:

MRP2

Inheritance:

Autosomal Recessive

Symptoms:

Does not give symptoms except a black liver

Blood Test:

Raised conjugated bilirubin

Management:

Usually no treatment is required

Rotor Syndrome

This is a syndrome similar to Dubin-Johnson. The problem here is that there is defective hepatic uptake and storage of bilirubin.

Gene:

SLCO1B1/3

Inheritance:

Autosomal Recessive

Symptoms:

Similar to Dubin-Johnson syndrome but does not give a black liver

Blood Test:

Raised conjugated bilirubin

Management:

Usually no treatment is required