Metabolic, Inherited Liver Disease: Waters

Question 1

Understand the mechanisms of hemochromatosis

Answer 1

Most common genetic condition in Caucasians. 1:200
Less hepcidin (regulates Fe levels), more Fe absorbed from duodenum.
Higher hepcidin = v Fe abs.
Lower hepcidin = ^ Fe abs.

Human hemachromatosis protein encoded by HFE gene. “HFE= High Fe”
C282Y gene mutation. Homozygotes def. have disease. 15% w/ dz will not have this mutation.

Excess Fe in tissues increases oxidative stress and free radicals.
Susceptible tissues have high # of transferrin receptors: heart (restrictive cardiomyopathy), liver (cirrhosis, hepatocellular carcinoma), pancreas (diabetes), thyroid

Question 2

Understand the mechanisms of Wilson’s disease.

Answer 2

1:100,000
Excessive Cu deposition
Complications: Chronic hepatitis, cirrhosis, acute liver failure. Psych issues. Kidney failure. Hemolytic anemia.
ATPase deficiency—> low cerulosplasmin, high free Cu in plasma, high Cu in liver, high urine Cu
Classically: a young person with psych issues and ALF.
LOOK FOR COPPER ACCUMULATION IN THE CORNEA (Kayser-Fleischer ring)!!

Question 3

Review the mechanisms of a1-antitrypsin deficiency and the hepatic complications.

Answer 3

Genetic defect in a1-antitrypsin TRANSPORT.
Phenotypes:
MM- good MZ- bad ZZ- really bad
Leads to low a1AT levels in serum and lung, but excess in liver.
Suspect in pts w/ emphysema w/ liver dz.

Question 4

How do you dx hemochromatosis?

Answer 4

Calculate for excess plasma Fe:
Serum Fe/Serum transferrin X 100
> 45%, suspect Fe overload

Question 5

Serum ferritin > 1000mcg/L predicts:

Answer 5

advanced fibrosis/cirrhosis

Question 6

Tx for hemochromatosis:

Answer 6

Removal of excess Fe: 
-therapeutic phlebotomy
- Fe chelating agents, bind Fe and remove through urine. (Desferoxamine IV)
Avoid vit. C (incr. Fe abs)
Avoid EtOH

Question 7

Dx for Wilson’s dz?

Tx for Wilson’s dz?

Answer 7

Dx: Serum ceruloplasmin, Serum free Cu, 24 hr urine Cu, liver biopsy

Chelation in mild dz
Liver transplantation in severe dz

Question 8

Dx for a1-AT deficiency?

Tx for a1-AT deficiency?

Answer 8

Dx: liver biopsy, genotype

Tx:
Lung: replace enzyme.
Liver: transplant, treat cirrhosis.