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Chapter 5: Disorders of the liver 211

accumulates in the tissues as haemosiderin particularly Wilson’s disease
within the liver, pancreas, pituitary, heart and skin.
Definition
Hepatocyte necrosis leading to cirrhosis.

Inherited disorder causing copper accumulation in the
Islet cell death, leading to diabetes mellitus.

liver, brain, kidney, cornea and bone.
Cardiomyopathy and heart failure.

Pituitary and gonadal abnormalities.

Prevalence
Rare; 1 in 50,000 of the population.
Clinical features
Pigmentationoftheskin(duetoincreasedmelanin),dia- Age
betes and hepatomegaly is the classical description of the May present at any age. Unusual before 5 years.
disease. Arthritis due to calcium pyrophosphate deposi-
tion may occur, usually affecting the knees and meta- Sex
M = F
carpophalangeal joints. Other presenting features in-
clude pituitary dysfunction, cardiac enlargement and/or
Aetiology
failure.
Inherited in an autosomal recessive manner. The muta-
tion is in a copper-transport ATPase gene on chromo-
Macroscopy/microscopy some 13.
The tissues appear rusty brown. The iron is mainly
around the portal tracts. Portal fibrosis is seen, prior Pathophysiology
to cirrhosis. In Wilson’s disease the mutation is thought to affect the
excretion of copper from hepatic lysosomes into the bile.
Excess copper in the hepatocytes causes lipid to collect
Complications
in the cytoplasm. There is increasing inflammation and
There is a high risk of hepatocellular carcinoma if cir-
fibrosis and untreated, it progresses to cirrhosis.
rhosis develops.
Clinical features
Investigations Heterozygous individuals are asymptomatic and usually
Diagnosed on liver biopsy. have a completely normal copper balance. In homozy-
1 Liver function tests may be normal. gotes, the condition may present with acute hepatitis or
2 Serum iron is high, with >90% saturation of total iron may remain clinically silent until cirrhosis is established
binding capacity. or neurological symptoms develop including reduced
3 Serum ferritin is a measure of the total body iron con- performance at school, clumsiness or slurred speech.
tent and is useful for follow-up. Kayser–Fleischer rings (green/brown rings around the
edge of the cornea) are a late diagnostic sign, but are
variably present.
Management
Regular venesection reduces the iron load and the risk
Microscopy
of cirrhosis and hepatocellular carcinoma. Other man-
Excess copper can be seen in the liver using special stain-
ifestations are treated symptomatically, e.g. insulin for
ing. Itis ∼2–20 × normal, but this also occurs in chronic
diabetes, testosterone for gonadal failure. First degree
cholestatic disorders, such as primary biliary cirrhosis.
relatives should undergo screening with serum ferritin
levels.
Investigations
Reduced serum copper and ceruloplasmin levels (not
Prognosis specific and 25% of patients will have normal levels).
The earlier the diagnosis and treatment, the better the Urinary copper is high and increases markedly following
prognosis. With treatment, symptoms tend to improve, atest dose of d-penicillamine. A slit-lamp examination
including diabetes. However, cirrhosis is not reversible. of the eyes should be performed.