Flashcards in Metabolic liver disease Deck (17):
What is Wilson's disease?
genetic disorder in which copper accumulates in the tissues - mainly the liver and basal ganglia of the brain
What are the genetics of Wilson's disease?
due to mutations in the Wilson disease protein (ATP7B) gene on chromosome 13
autosomal recessive - 1/100 are carriers
What are the characteristic features of Wilson's disease?
abnormal transaminases and bili
Keiser-Fleischer rings - pathognomonic
Low ceruloplasmin - major copper-carrying protein in the blood
elevated urine copper (24 hour collect)
paradoxically low serum copper levels
How is Wilson's disease diagnosed?
Liver biopsy - A level of 250 μg of copper per gram of dried liver tissue confirms Wilson's disease
early findings show steatosis with progression on to fibrosis and cirrhosis
What are the neuropsychiatric symptoms of Wilson's disease?
initial mild cognitive deterioration and clumsiness and behavioural change
'wing beating tremor'
cognitive - frontal lobe disorder and subcortical dementia
Depression, anxiety and psychosis
How do people present with Wilson's disease?
- liver disease and neuropsychiatric symptoms are the main features that lead to diagnosis
- young people with abnormal LFTs
- Some are identified only because relatives have been diagnosed with Wilson's disease
5% are diagnosed with fulminant hepatic failure, usually in the context of a haemolytic anaemia
What are the liver complications of Wilson's disease?
Chronic liver disease
Cirrhosis -> portal HTN, ascites, encephalopathy, varices, splenomegaly
Risk of development to HCC is low even if cirrhotic
What other organ's can be affected in Wilson's disease?
Eyes - Keiser-Fleischer rings: accumulation of copper in the cornea
Kidneys - RTA
Heart - cardiomyopathy from copper accumulation
Hypoparathyroidism, recurrent miscarriage, infertility
What is the treatment for Wilson's disease?
low copper diet
- Penicillamine - binds copper which is then excreted in the urine
-> SEs include worsening of neuropsychiatric symptoms, drug-induced lupus, myasthenia -> stop
- Trientine hydrochloride if unable to have penicillamine
Zinc can be used as maintenance once copper level have normalised
Patients who are asymptomatic are still treated to prevent long-term sequellae
- mainly in people with fulminant liver failure
- failure to respond to medical treatment
- advanced chronic liver disease
- avoided in severe neuropsychiatric illness, in which its benefit has not been demonstrated
What is the pathophysiology behind Haemochromatosis?
Mutations in HFE gene cause increased release of Hepcidin by the liver
Hepcidin increases iron absorption from duodenal cells causing iron overload
What are the most common alleys causing hereditary haemochromatosis
C282Y (major risk allele) and H63D (minor risk allele)
- mis-sense mutations
What is the prevalence of HH allele mutations and phenotypic disease?
Mutations - 40% (highest in caucasion population)
Phenotypic disease in 0.3%
What are the clinical features of iron overload?
chronic liver disease
- hepatomegaly, abnormal LFTs, fibrosis, cirrhosis risk of HCC
- 2nd, 3rd MCPs
- T1DM (consider in later onset), hypogonadism – decreased libido, gynaecomastia, amenorrhoea
– cardiomyopathy, CHF, arrhythmias
What is the most sensitive initial screening test for haemochromatosis?
Transferrin saturation > 45%
- this will detect almost all C282Y homozygotes
the combination of a normal transferrin saturation and a normal ferritin has a NPV of 97%
What are other causes of iron overload other than HH?
- Iron loading anaemias
o Thalassaemia major
o Sideroblastic anaemia
o Chronic haemolytic anaemia
- Multiple transfusions
What is the treatment and targets for HH?
Venessection to target ferritin 50 - 100 whilst maintaining Hb/HCT not less than 80%