Pediatric Liver Disease

Question 1

What is physiologic jaundice?

Answer 1

Enhanced BR production due to large RBC mass, shortened RBC life span or inefficient erythropoiesis
Decreased albumin binding
Decreased hepatic uptake/binding due to decreased lignin
Decreased conjugation
Decreased secretion

Question 2

Neonatal cholestasis: Describe intrhepatic (2) and extrahepatic (2) causes

Answer 2

Neonatal cholestasis is an emergency

Intrahepati causes: Neonatal hepatitis and alagille syndrome
Extrahepatic: choledochal cyst and biliary atresia

Question 3

Describe the epidemiology of biliary atresia

Answer 3

Most common cause of infantile cholestatic jaundice
Only occurs in infants
Leading indication for liver tx

Question 4

Biliary Atresia: What are the classifications?

Answer 4

Idiopathic isolated biliary atresia (80%)
Malformation related (20-30%)

Question 5

Biliary Atresia: presentation

Answer 5

Well appearing child with echoic stools and dark urine, mild icterus, hepatosplenomegaly

Lab: Elevated conjugated BR, ALT, GGT

Question 6

What are tests that are run in case of neonatal cholestasis?

Answer 6

Ultrasound: detect abnormalities (choledochal cyst, bile duct stones, perforation of common bile duct, polysplenia)
Disida scintiscan to look out excretion and rule out biliary atresia 
Percutaneous liver biopsy
Operative cholangiogram (gold standard)

Question 7

What is histological finding on biopsy of biliary atresia? (3)

Answer 7

Bile duct proliferation
Ductal bile plugs
Portal fibrosis

Question 8

What is treatment strategy for biliary atresia?

What factors influence outcome? (2)
What measurement signals success/failure?

Answer 8

Kasai hepatoportoenterostomy– outcome is influenced by age at surgery (

Question 9

What are the complications associated with biliary atresia? (list)

Answer 9

Persistent jaundice
Intratable pruritis
Ascending cholangitis
portal hypertension, splenomegaly
Variceal hemorrhage
Fat-soluble vitamin deficiencies
Failure to grow
Liver tx (chronic liver failure)

Question 10

Describe models for pathogenesis of biliary atresia

Answer 10

Perinatal: environmental factors, inflammatory response, genetic predisposition (Notch, HLA, immune)==>Immune response
Embryonic: Genetic predisposition, abnormal biliary development, common bile duct obstruction==>Bile flow injury

Question 11

What is candidate gene for biliary atresia?

Answer 11

Deletion of GPC1 on chromosome 2 results in abnormal biliary development

Question 12

Glyogen storage disease: Presentation (2), biopsy findings

Answer 12

Hepatomegaly and hypoglycemia

On biopsy, observe glycogen granules in hepatocytes on PAS stain. In some types of GSD may also see glycogen in muscle

Question 13

Which storage disease is associated with hepatosplenomegaly?

Answer 13

Riemann Pick Disease– abnormal lipids accumulate in reticuloendothelial cells

Some types have neurologic involvement

Question 14

How do patients with tyrosinemia present?

How can you improve liver function?

Answer 14

Coagulapathy, early liver failure or cirrhosis
High risk of HCC

Improve liver function via drug to block metabolic pathway

Question 15

What are leading inherited causes of cirrhosis in kids? (5)

Answer 15

A1AT deficiency
PFIC
CF
Wilson's disease
Hemochromatosis

Question 16

What is major leading cause of inherited cirrhosis in adults?

Answer 16

Hemochromatosis….A1AT ranked second

Question 17

What is A1-Antitrypsin deficiency?

Answer 17

Autosomal recessive deficiency in serum protease inhibitor that inhibits neutrophil elastase in lung

Question 18

What is presentation of A1AT deficiency?

Answer 18

Early emphysema in 3rd/4th decade

A subset develop liver disease due to accumulation of mutant protein in hepatocytes– observe neonatal hepatitis, chronic hepatitis, cryptogenic cirrhosis, HCC

Question 19

A1AT Deficiency: Diagnosis

Which phenotype of A1AT is associated with liver/pulmonary disease?

Answer 19

PCR stuff to identify protein phenotypes–
PIMM=full functional activity
PIZZ=liver/pulmonary disease

Question 20

How is A1AT deficiency managed? (4)

Answer 20

No smoking
Treat complications
Monitor for HCC
Liver/lung tx

Question 21

What is a new approach for A1AT?

Answer 21

Enhance autophagy==>carbamazepine to destroy cells with protein accumulation

Question 22

What is Wilson Disease?

Answer 22

Copper accumulation in liver and brain due to defective hepatic excretion of copper (gene is ATP7B on chromosome 13)

Question 23

Describe copper trafficking in Wilson Disease

Answer 23

Defective ATP7B cannot transport copper into golgi for exocytosis and transport via ceruloplasmin.

Accumulation of copper in cytoplasm causes mitochondrial damage and cellular damage

Question 24

What is clinical presentation of Wilson Disease?

Answer 24

Hepatic disease at school age: elevated ALT/AST, hepatomegaly, chronic hepatitis, cirrhosis, fulminant hepatitis, autoimmune hepatitis appearing

Neuro: dystonia with rigidity, tremors, dysarthria, dysphonia, gait disturbance, choreiform movements

Other: renal disease, psych disease, cardiomyopathy, arthritis

Question 25

Wilson Disease: Diagnosis

Answer 25

Ceruloplasmin level (

Question 26

Wilson Disease: Treatment (4)

Answer 26

Oral chelating agents (penicillamine, trientene, tetrathiomolybdate)
Zinc: blocks Cu absoprtion
Liver tx: fulminant/chronic liver disease
Low copper diet and antioxidants

Question 27

What is genetic hemochromatosis?

How common is it?

Answer 27

Autosomal recessive disorder resulting in deposition of iron in parenchymal cells and cell damage and functional abnormalities

Prevalence: 1/200 white people (less than 1/300 are symptomatic)

Question 28

Describe normal iron homeostasis

What is the role of hepcidin?

Answer 28

Iron absorption tightly controlled by enterocytes
Recycling by macrophages
Storage by hepatocytes

Hepcidin=hormone synthesized in liver based on iron levels, infection, inflammation, anemia

Question 29

What factors are important in having clinical manifestations of disease? (4)

Answer 29

Diet, blood loss, alcohol

HFE mutation

Question 30

What is the classic triad of hereditary hemochromatosis?

What are other symptoms may be visible

Answer 30

Hepatomegaly, DM, skin pigmentation

Abdominal pain, weakness, lethargy, arthralgias, cardiac disease, infections may also be signs

Question 31

What is epidemiology of hereditary hemochromatosis? Age, sex

Answer 31

Mean age=50yo

M>W (blood loss due to menses may be protective)

Question 32

Diagnostic criteria for hereditary hemochromatosis

Answer 32

Slightly elevated serum Fe
High transferrin saturation
Very high ferritin
Very high hepatic Fe content

Question 33

What is therapy for hemochromatosis?

Answer 33

Removal of Fe by phlebotomy weekly/biweekly

This does not improve fixed tissue complications so it is important to identify disease early and start treatment