Wilson's disease is an inherited disorder that causes copper to accumulate in the liver and other organs. This document discusses the pathophysiology, clinical manifestations, diagnosis, and treatment of Wilson's disease. It provides guidelines from the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. Key points include that Wilson's disease should be considered for any unexplained liver or neurological conditions, a low ceruloplasmin level supports the diagnosis, treatment is lifelong chelation therapy or zinc, and liver transplantation may be needed for decompensated cirrhosis.
6. KF Ring
Neuropsychiatric: 99% .
Hepatic : 30 to 50 %
KF rings are not specific
for WD.
They may be found in
other chronic
liver disease, PBC, PSC,
AIH, and familial
cholestatic syndromes.
7. PSYCHIATRIC PRESENTATIONS
15-20% of patients may present with
purely psychiatric symptoms .
◦ Phobias ,
◦ compulsive behaviors,
◦ aggressive and antisocial behaviors
◦ Schizophrenia
◦ Psychosis
◦ Cognitive decline
8. HEPATIC PRESENTATION
Acute hepatitis,
Chronic liver disease— portal HTN.
Autoimmune hepatitis.
Fulminant hepatic failure, with sev.
coagulopathy and encephalopathy .
Recurrent bouts of hemolysis may
predispose to the development of
gallstones .
Wilson disease is rarely complicated by
hepatocellular carcinoma.
11. MRI appearance in WD
a. ‘Face of giant panda’
sign;
b. MRSS: decreased NAA
and therefore a
decreased ratio with
other products
c. Bright lateral putamen
or claustral sign;
d. Pallidal hyperintensity
12. Unexplained CLD
Diagnosis of WD
KF Ring +
CPN
< /
24h.U.cu>
40
KF Ring +
CPN=20
24h.U.cu>4
0
Liver biopsy-
histology &cu
quantification
Molecular
testing
KF Ring-
CPN <20
24h.U.cu=>4
0
KF Ring –
CPN<20
24h.U.cu >40
>250mcg
/g
70-
250mcg/g
<50
mcg/g
Other
diagnosis
13. Neuropsychiatric +-
CLD
Diagnosis WD
KF Ring +
CPN>=20
24hU.cu>
40
KF Ring +
CPN>20
24hU.cu<40
Other Dx
KF Ring-
CPN <20
24hU.cu>40
KF Ring +
CPN <20
24hU.cu>40
Liver biopsy cu
quantification
Molecular
testing
>25070-
250
17. DISEASE SEVERITY ASSESMENT BY
NAZAR PROGNOSTIC INDEX…
Scores< 7 medical theraphy
>9 immediate LT
7-9 clinical judjment – Rx or
LT???(trientine & Zinc acetate)
With Rx-LFT usually recovers in about 1
year..
Neurologic & psychiatric mane. usually
improve after 6-24 months….
Residual liver damage may persist.
18. Family Screening
Biochemical Testing
◦ Children of patient: Begin at age 2 if asymptomatic,
repeat once in 5 years unless reason to pursue
further.
Siblings of patient:
◦ Physical examination and brief history of any liver
or neurological symptoms.
◦ Liver Function Tests: ALT, AST, Albumin, Bilirubin.
◦ Ceruloplasmin and Serum Copper.
◦ 24 hour urine copper
◦ Slit-lamp exam of the eyes for Kayser-Fleischer ring
◦ If no K-F rings, abnormal liver functions tests, and
low ceruloplasmin: liver biopsy.
20. Wilson’s disease should be considered in
any individual with liver abnormalities
or neurological movement disorders
of uncertain cause.
Age alone should not be the basis for
eliminating a diagnosis of Wilson’s disease
GRADE II-2, A, 1
AASLD Class I, Level B
21. Wilson’s disease must be considered in
any patient with unexplained liver
disease in combination with
neurological or neuropsychiatric
disorders
GRADE II-2, A, 1
AASLD Class I, Level B
22. Kayser-Fleischer rings should be
sought by slit-lamp examination by a
skilled examiner.
The absence of Kayser-Fleischer rings
does not exclude the diagnosis of
Wilson’s disease, even in patients with
predominantly neurological disease
GRADE II-2, A, 1
AASLD Class I, Level B
23. Neurologic evaluation and imaging of the
brain, preferably by MR imaging, should
be considered prior to treatment in all
patients with neurologic Wilson’s disease
and should be part of the evaluation of
any patient presenting with neurological
symptoms consistent with Wilson’s
disease
GRADE II-2, B, 1
AASLD Class I, Level C
24. A low serum ceruloplasmin
level(<50mg/dl) should be taken as
evidence for the diagnosis of WD.
Borderline levels require further
evaluation.
Serum ceruloplasmin within the normal
range does not necessarily exclude the
diagnosis
GRADE II-2, A, 1
AASLD Class I, Level B
25. Basal 24-hour urinary excretion of copper
>1.6 μmol/>100micg is typical in
symptomatic patients.
>0.6mic may indicate WD & needs Ix.
Penicillamine challenge test is rec. in pt
with <1.6mic
In children with mild hepatic disease
basal 24-hour urinary excretion of copper can
only be mildly elevated or may even be
in the normal range.
Lowering the threshold to >0.64 μmol/24 hr
may be useful for detecting asymptomatic
patients but this will be less sensitive and will
overlap with patients with other liver injury
GRADE II-2, B, 1
AASLD Class I, Level C
26. Hepatic parenchymal copper content
>4 μmol/g or >200micg dry weight
provides critical diagnostic information
and should be obtained in cases where
the diagnosis is not straightforward and
in younger patients.
In untreated patients, normal hepatic
copper content (<0.64-0.8 μmol/g dry
weight) almost always excludes a
diagnosis of Wilson’s disease
GRADE III, B, 2
AASLD Class I, Level B
27. Mutation analysis with specific allelic
probes or by whole-gene sequencing is
currently possible and available.
Specific testing for known mutations or
screening of first-degree relatives of
patients with haplotype analysis should be
the primary mode for Wilson’s disease
GRADE II-2, B, 1
AASLD Class I, Level B
28. Initial treatment for symptomatic patients
with Wilson’s disease should include a
chelating agent (D-penicillamine or
trientine).
Trientine may be better tolerated
GRADE II-1, B, 1
AASLD Class I, Level B
29. Zinc may have a role as a line therapy in
neurological patients
GRADE II-2, C, 2
AASLD Class II, Level C
30. Treatment of presymptomatic patients or
those with neurological disease on
maintenance therapy can be accomplished
with a chelating agent or with zinc
GRADE II-1, B, 1
AASLD Class I, Level B
31. Treatment is lifelong and should not be
discontinued, unless liver transplantation
is performed
GRADE II-1, B, 1
AASLD Class I, Level B
32. If zinc is used, careful monitoring of
transaminases is needed, with changing
to chelators if these laboratory
parameters are increasing
GRADE C1
AASLD Class I, Level B
33. Patients should avoid intake of foods and
water with high concentrations of copper,
especially during the year of treatment
GRADE II-3, B, 2
AASLD Class I, Level C
34. Patients with acute liver failure due to
Wilson’s disease should be treated with
liver transplantation when the revised
King’s score is 11 or higher.
GRADE II-2, B, 1
AASLD Class I, Level B [41
35. Patients with decompensated cirrhosis,
unresponsive to chelation treatment,
should be evaluated promptly for liver
transplantation
GRADE II-2, B, 1
AASLD Class I, Level B
36. Treatment for Wilson’s disease should be
continued during pregnancy, but
dosage reduction is advisable for D-
penicillamine and trientine
GRADE II-3, B, 1
AASLD Class I, Level C
37. For routine monitoring, serum copper
and ceruloplasmin, liver enzymes an
international normalized ratio, functional
parameters, complete blood count and
urine analysis as well as physical and
neurologicalexaminations should be
performed regularly, at least twice
annually
GRADE II-2, B, 1
AASLD Class I, Level C
38. The 24-hour urinary copper excretion on
medication and after 2 days of
cessation of therapy should be
measured at least yearly.
The estimated serum non-ceruloplasmin
bound copper may be another useful
parameter to control therapy
GRADE II-3, B, 1
AASLD Class I , Level C
39. REFFERENCES-
EASL Clinical Practice Guidelines: Wilson’s
disease-European Association for the
Study of the Liver-june 2012
AASLD PRACTICEGUIDELINES-Diagnosis
and Treatment of Wilson Disease:An
Update-Eve A. Roberts and Michael L.
Schilsky-2012 vol 56
Harrison’s principles of Internal medicine-
18th edition