Aims: The histochemical demonstration of hepatic copper is important i
n the diagnosis of Wilson's disease (WD). Conflicting results have bee
n published with regard to the ability of different histochemical meth
ods to demonstrate copper storage in the liver, Therefore, we evaluate
d the diagnostic value of three available histochemical methods in a l
arge series of patients affected by WD. Methods and results: Seventy-n
ine consecutive liver needle biopsies, from 74 patients, 39 males and
35 females, aged 4-60 years (mean age 28.5 years) were stained with or
cein, rhodanine and using Timm's method. On the basis of the histologi
cal picture, liver biopsies were subdivided into three groups: group A
, steatosis: group B, interface hepatitis; group C, chronic hepatitis
with bridging fibrosis and/or cirrhosis, In group Al 30.4% of the case
s were positive using Timm's method, vs 13.2% using the rhodanine and
17.5% using the orcein method. In group B, Timm's method was positive
in 40.1% while rhodanine and orcein showed positivity in 26.7%. In gro
up C, the Timm's method stained 58.6%, rhodanine 36.6% and orcein 29.3
% positively, Conclusions: Our data show that: (1)Timm's silver stain
is the most sensitive method for the demonstration of copper in all ca
ses of WD; (2) rhodanine and orcein have minor value in the diagnosis
of WD, especially in the early stages of the disease; (3) to increase
the diagnostic value of histochemistry for copper multiple histochemic
al stains in serial sections are required: and (4) although hepatic co
pper concentration is highest in the early stages of WD, the histochem
ical demonstration fails in a large number of cases.