| Chronic liver disease
| Alkaline phosphatase (ALP)
| Liver Function Tests
| Ascites Assessment and Management
| Budd-Chiari syndrome
| Autoimmune Hepatitis
| Primary Biliary Cirrhosis
| Primary Sclerosing Cholangitis
| Wilson disease
| Hereditary Haemochromatosis
| Alpha-1 Antitrypsin (AAT) deficiency
| Non alcoholic steatohepatitis (NASH)
| Spontaneous Bacterial Peritonitis
| Alcoholism and Alcoholic Liver Disease
- HH is a condition caused by continued absorption of iron from the upper small intestine, despite normal, and then increased,total body iron.
- This leads to accumulation of iron in the tis-sues as the body has no means of getting rid of excess iron
- Autosomal recessive disease. Mutation on the gene for the HFE protein on Chromosome 6.
- Affected are homozygous for the C282Y mutation or C282Y/H63D.
- Homozygous 1:200 and a heterozygous frequency of 1:8 in Northern Europeans
- Most common single gene disorder in whites
- HFE codes for MHC class I like molecule which interacts with Beta2 microglobulin.
- Leads to increased iron uptake leading to cell injury and necrosis and fibrosis and cirrhosis develops.
- Less than 10% of those homozygous develop liver disease.
- Body iron rises from 4g to 40 g and induces Liver fibrosis.
- Females given some protection by menstruation
- 1/220 of Northern European ancestry are homozygous for mutation
- 1/11 are heterozygous; thus disease is very common
- Excessive deposition of iron, usually deposited in liver, pancreas and heart
- Normal iron is 0.5 g in liver and 98% of that in hepatocytes
- GH may exceed 50 g in liver (normal 2 - 6 g)
Prussian Blue stain shows iron within hepatocytes, initially heavy periportal parenchymal iron deposition with sparing of Kupffer cells
- Fatigue, malaise, apathy, weight loss
- Abdominal pain - hepatomegaly
- Secondary diabetes (pancreas deposition)
- Hypogonadism is seen due to pituitary disease
- Right and left heart failure and arrhythmias
- Dilated cardiomyopathy.
- Melanin deposition in skin with grey or bronzed look
- Arthritis - chondrocalcinosis, Testicular atrophy
- High Serum Ferritin (SF) levels > 500 ug/L
- Fasting Serum transferrin saturation (serum iron/(TIBC or Transferrin) x 100%) > 50% and often > 90%
- LFT's may be normal or elevated ALT and AST
- Low Total iron binding capacity Raised Serum Iron - elevated
- Genotyping by PCR for HFE mutations in selected patients
- Liver biopsy is no longer required for diagnosis but may be required to assess the severity of fibrosis in GH patients with SF >1000 mcg/l and/or ele-vated transaminases.
- Transient elastography could be used to select which patients from this group require liver biopsy.
- Testosterone low as FSH and LH low
- MRI - T2 Gradient return echo (GRE) shows Iron overload in liver and pancreas
- Check Negative HCV or HBV if risks
- Cirrhosis, Hepatocellular carcinoma
- Liver failure, Diabetes
- All adult patients of north European ancestry with unexplained raised SF and random Tsat (>300 mcg/l and>50% males; >200mcg/l and >40% females) and normal FBC should have molecular testing for HFEGH.
- Family screening should include parents (if available), siblings, partner andchildren (over the age of consent).
- Extended family screening is not recommended if an individual is identified as a C282Y/H63D compound heterozygote
- Patients who present with serum ferritin (SF) >1000 mcg/l and any with raised transaminases should be referred to a hepatologist for fibrosis assessment and exclusion of cirrhosis.
- All fit GH patients with biochemical ironloading should undergo weekly venesection until SF 20-30 mcg/l and Tsat <50%. This can be done at a blood donation centre. Keep SF <50 mcg/l and Tsat <50%.
- Venesection of 500 ml weekly for first 2 years limited only by an Iron deficiency anaemia
- This is followed by life long monthly or quarterly venesection
- Continue until transferrin saturation < 50% and ferritin level < 50 ng/ml
- Screen all first-degree relatives with Iron and transferrin saturation
- Screening of family members should be with HFE gene if the index case is C282Y/C282Y or H63D/C282Y.
- Patients with confirmed cirrhosis monitor with alpha-fetoprotein(AFP) and hepatic ultrasound every 6 months