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a total of 300 subjects seen from 1948 to 2000, Dr. John Walshe stated that the prin-
cipal cause of death in WD was a diagnostic failure [48]. The importance of diagno-
sis and prompt treatment institution in patients with WD is clear; thus, its exclusion
in evaluating patients with liver disease is warranted, regardless of hepatic
comorbidities.
Clinical Manifestations
Patients with WD may present without any signs or symptoms of liver disease. Most
patients present after the age of three, considered to be due to the large capacity of
the liver to accumulate copper. The most common presentation in children is liver
disease, usually between ages from 10 to 13 years, much earlier than the age at
which neurological manifestations become clinically apparent [49]. Ten percent of
the patients present with psychiatric manifestations, 35% with neurological disease,
and 45% with liver disease. Hemolytic anemia, cardiomyopathy, and altered thyroid
function are some of the other manifestations of the disease. The hepatic abnormali-
ties accompanying them should lead to the diagnosis [50].
Patients may exhibit physical ndings of liver disease; azure lunulae, i.e., blue
lunula due to copper deposition, in nails is described [51].
The Kayser–Fleischer (KF) ring is described as a dark band of pigment in the
Descemet membrane of greenish yellow to golden brown color, which is comprised
of copper [52]. In a study that included 55 patients with WD prior to treatment, KF
rings were documented in 55%, with a proportion of 90% with neurological mani-
festations exhibiting this nding [53]. Sunower cataracts is another ophthalmo-
logical manifestation of WD [54]; they were documented in 1.2% of 81 newly
diagnosed patients with WD with a mean age of 32.3±11.8years 42% of whom
had neurological manifestations [55]. This type of cataract is described as a thin,
centralized opacication under the anterior capsule and occupying one-third to one-
half of the anterior lens pole surface area, with opacications emanating from the
center that give the impression of sunower [55].
A study that examined retrospectively the documented neurological examina-
tions of a group of 119 patients reported that symptoms tended to start at a mean age
of 19 years, with a range from 7 to 37, with dysarthria being the rst one in 91% of
patients, gait abnormalities in 75%, risus sardonicus in 72%, dystonia in 69%, rigid-
ity in 66%, tremor in 60%, dysphagia in 50%, chorea in 16%, and athetosis in 14%;
seizures and pyramidal signs were present in less than 5% of patients [56]. The cli-
nician must be cognizant of WD’s signs, labeled “A Great Masquerader” by the
authors of a publication from a retrospective study of 50 patients referred to a uni-
versity hospital and private clinic in Tehran from 1984 to 2004 [57]. The median age
of onset of neurological symptoms or both hepatic and neurological manifestations
ranged from 10 to 38years, with a mean of 16, in contrast to patients with initial
ndings of liver disease, who exhibited neurological symptoms at a mean age of 18
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years, with a range from 11 to 34, with dysarthria being the most common, i.e., in
80% of patients, as described in the prior study [56]. Drooling was present in 48%
of patients, 44% had limb tremors, abnormal gait, alone or in combination with
psychiatric and sleep alterations, and 42% had dystonia. Of note, a review of WD
that included studies conducted over 66years reported that 30–40% of patients have
psychiatric manifestations at the time of diagnosis, and 20% had seen a psychiatrist
prior to the diagnosis of WD [58]. As documented in these two studies, manifesta-
tions of WD tend to become apparent before age 40; however, late clinical presenta-
tions are well documented [59].
The clinical and genetic characterization of 46 of 1223 (3.8%) patients, 1053 of
whom were index cases, and 170 siblings, who manifested clinically after the age of
40 was described [59]. Thirty-one (67.4%) patients presented with neurologic
symptoms at a mean age of 44.5years, with a range from 40 to 52; 15 (32.6%), 9 of
whom were women, presented with liver disease at a mean age of 47years, with a
range from 40 to 58, and 2 (4.3%) were asymptomatic siblings. One patient’s
hepatic presentation was fulminant, with the rest having abnormal liver tests, hepa-
tomegaly, or both. Of note, from the 13 patients from whom liver histology was
available and who presented with liver test abnormalities, 10 had cirrhosis, 2 chronic
hepatitis, 1 steatosis, and 1 did not have any histological abnormalities. Twenty-
seven of the 46 index cases had mutations on both chromosomes and included
H1069Q/H1069Q in 13, and in one chromosome in another 13. The authors con-
cluded that WD could be “overlooked.” The clinical characteristics of patients who
presented after age 40in this study were similar to those of the patients who present
early in life, which suggested that other factors inuence WD’s clinical expression.
Conversely, the case of a 9-month-old baby who exhibited abnormal liver panel was
diagnosed with WD by genetic testing [60] and that of a 10-year-old boy who pre-
sented with a 3-month history of leg muscle cramps has been described. Again, as
previously stated, “the principal cause of death in Wilson (‘s) disease was diagnostic
failure” [48].
Acute Liver Failure
By denition, acute liver failure is the loss of liver function in patients without prior
liver disease [61–64]; as inferred, it is characterized by hepatitis, associated with
hepatic synthetic dysfunction, and hepatic encephalopathy developing over less
than 8–12 weeks [64]. In WD, however, acute liver failure can be a presentation in
patients with chronic liver disease, i.e., brosis and sometimes, cirrhosis. Acute
liver failure from WD is fatal in the majority of patients without liver transplanta-
tion; accordingly, early recognition and transfer to a liver transplantation center are
fundamental in the management of patients who present with this complication.
Prognostic indeces to predict survival in patients with acute liver failure from WD
have been developed [65, 66].
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Five percent of the patients referred for liver transplantation because of acute
liver failure have WD.The female-to-male ratio of patients with acute liver failure
due to WD is 2:1 to 4:1. A study that included 140 patients with acute liver failure,
16 of whom had WD, 17 had treated chronic WD, and 29 other chronic liver dis-
eases documented that a ceruloplasmin level of less than 20mg/dl by the oxidase
method had a diagnostic sensitivity of 21%, and specicity of 84%; when measured
by nephelometry, the sensitivity was 56% and specicity 63%. Serum copper levels
were higher than 200 micrograms/dl in all patients with acute liver failure from
WD.A serum alkaline phosphatase to total bilirubin ratio less than 4, had a sensitiv-
ity of 94% and a specicity of 96%, while an AST-to-ALT ratio greater than 2.2 had
a sensitivity of 94% and a specicity of 86% with the combination of all tests giving
a diagnostic accuracy of 100% [67].
Liver Histology
The liver histology in patients who present with acute hepatitis exhibits ballooned
hepatocytes, acidophilic bodies, cholestasis, and scant lymphocytic inltration. The
pre-cirrhotic liver in WD shows anisonucleosis, focal necrosis, few sinusoidal aci-
dophilic bodies, and moderate to marked steatosis. Glycogenated bodies, steatosis,
moderate to marked copper accumulation, and Mallory bodies are seen in periportal
hepatocytes [68]. In young, asymptomatic patients, copper accumulates itself in the
cytoplasm of the hepatocytes. In contrast, in patients who present symptoms and
signs of the disease, copper is widely distributed including inside the lysosomes. In
the cirrhotic stage, copper is limited to the lysosomes. The p- dimethylaminobenzylidene
rhodanine gives reproducible staining ndings.
Cirrhosis in WD tends to be macronodular, but it can be mixed, with minimal
bile ductular proliferation noted in the nodules’ brous bands. Mallory bodies can
be found in the periphery of the cirrhotic nodules.
Mitochondrial abnormalities were reported as distinctive in WD and included
heterogeneity of size and shape, increased matrix density, separation of inner from
outer membranes, and enlarged intercisternal spaces [68]. In association with che-
lating therapy with DPA for three to ve years, mitochondrial abnormalities were
documented to be less notable than at baseline or absent [69].
Laboratory Findings
Patients can exhibit increased serum activity of transaminases or ndings sugges-
tive of portal hypertension from cirrhosis with or without hepatic synthetic dysfunc-
tion; typically, serum activity of alkaline phosphatase is low or in the low limits
of normal.
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Diagnostic Investigations
The specic laboratory ndings in WD are ceruloplasmin concentration less than
20mg/dl, serum free or non-ceruloplasmin-bound copper less than 100 micrograms/
dl, hepatic copper content greater than 250 micrograms/gram of dry weight, and
urinary copper content greater than 100 micrograms per 24h. Genetic testing is
done to identify mutations in the ATP7B gene. Guidance on the diagnosis and treat-
ment of WD is available from the American and the European Associations for the
Study of Liver Diseases [70, 71].
Imaging Studies
Magnetic resonance imaging (MRI) of the brain has provided the feature now rec-
ognized as typical of WD, the “face of the giant panda” sign. It has been recognized
to distinguish WD from other early onset extrapyramidal disorders. A retrospective
review that included images from 100 patients identied, specically in patients
with WD, the following ndings: (1) “Face of giant panda” sign in 14.3%, (2) tectal
plate hyperintensity in 75%, (3) central pontine myelinolysis-like abnormalities in
62.5%, and concurrent signal changes in basal ganglia, thalamus, and brainstem in
55.3%. The authors concluded that in addition to “Face of giant panda” sign, hyper-
intensities in the tectal-plate and central pons, and simultaneous involvement of
basal ganglia, thalamus, and brainstem are “virtually pathognomonic” of WD [72].
Resolution of MRI ndings in the globus and caudate regressed in association with
liver transplantation over 2 years of follow-up in a 28-year-old patient [73].
Transient Elastography
The experience in transient elastography with FibroScan® is still limited; however,
a value of 6.6kPa is considered suggestive of mild and moderate brosis, whereas
a value higher than 8.4 is indicative of severe brosis. More studies are now neces-
sary to conrm the usefulness of FibroScan® in managing chronic therapy for WD
patients [74].
Screening inWilson’s Disease
Siblings and rst-degree relatives of patients with diagnosed WD must be screened
for the disease.
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Clinical manifestations of liver and neurological disease, alone or in combina-
tion should trigger suspicion for WD; in children, sudden poor school performance
and behavioral problems should be considered indications for excluding the disease.
The clinical investigations include hepatic panel, hemogram, serum ceruloplas-
min, 24-h urine for copper, serum copper, and referral to ophthalmology for slit
lamp examination to exclude KF rings. Liver biopsy for copper quantitation and
genetic testing can be included, according to published guidelines [70, 71]. In
regards to liver histology, a biopsy is recommended when the combination of clini-
cal signs and laboratory tests are not conclusive, or to exclude hepatic comorbidities
[75]. The Leipzig score (Table 12.1) was developed to facilitate the diagnosis of
WD; diagnostic algorithms have been derived from that score [70, 76, 77]. In
patients with symptoms suggestive of WD, including extrapyramidal symptoms, KF
rings, and low serum ceruloplasmin, a score between 0 and 3, should be followed by
a 24-h urine collection of copper. If the urine copper concentration is greater than
1.6 micromols/24hr. (100 microg/24hr) (0.64 micromoles per day in children), a
Table 12.1 Leipzig Score for the diagnosis of Wilson’s Disease (WD) [76]
Clinical ndings suggestive of WD
Additional
Investigations
Points Points
KF rings Liver copper concentration (in the
absence of cholestasis)*
Present 2 > 4 micromol/g 2
Absent 0 0.8–4 micromol/g 1
Normal (0.8 micromoles/g) − 1
*Rhodadine-positive granules 1
Neurologic symptoms or typical brain
magnetic resonance imaging ndings
24-hour urine for copper
▫
Severe 2 Normal 0
Mild 1 1–2 x ULN 1
Absent 0 > 2 x ULN 2
Normal at baseline with an increase
5 X ULN after DPA
2
Serum ceruloplasmin Genetic analysis
Normal (>0.2g/L) 0 Mutations in 2 both chromosomes 4
0.1–0.2g/L 1 Mutations in 1 chromosome 1
< 0.1g/ml 2 No mutations 0
Hemolytic anemia, Coomb’s negative
Present 1
Absent 0
▫: in the absence of acute hepatitis in regards to the urine collecdtion
DPA: D-penicillamine
*If the concentration of liver copper is not available
Summation of Scores
4 or more: diagnosis established
3: possible diagnosis; additional tests required (e.g., genetic testing, hepatic copper concentration)
2 or less: diagnosis is unlikely
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liver biopsy for copper quantitation with a value of fewer than 4 micromoles per
gram excluding WD in patients with a score of 0–1 but, in patients with a score
equal or less than 3, mutation analysis is recommended for diagnosis. One of two
mutations conrms the diagnosis, with an increase in the score to at least 4. In
patients with a hepatic copper concentration greater than 4 micromols/g, a score
increases to at least 4, which conrms the diagnosis.
Treatment for WD should be started immediately after diagnosis.
Treatment
The American and European Associations for the Study of Liver Diseases have cre-
ated guidelines for the treatment of WD [70, 71].
The starting dose of DPA is 250–500mg/day, increased by 250mg weekly, to a
maximum of 1000 to 1500mg per day in divided doses, taken 1 h before or 2 h after
meals. The dose for children is 250mg daily, with a maximum of 20mg per kg, in
divided doses. After the initial decoppering, which tends to occur between four to 6
months after initiation of treatment, a maintenance dose of 750–1000mg per day in
two divided doses is sufcient during the maintenance phase, usually after 4–6
months. The therapeutic response to changes in the maintenance dose usually will
not become evident for 4–6 weeks [70, 71]. DPA can be administered during preg-
nancy. DPA can be associated with pyridoxine deciency because of pyridoxine
kinase inhibition; thus, pyridoxine is supplemented at doses of 25 to 50 mg orally
per day during treatment [70, 71].
DPA can be associated with sensitivity reactions characterized by fever, rash,
lymphadenopathy, bone marrow suppression, and proteinuria; follow-up is impor-
tant to identify any side effects that can present after years of therapy. If these com-
plications occur, the drug should be discontinued and the patient treated with an
alternative medication.
Trientine (trimethylene tetramine dihydrochloride) is a chelating agent promot-
ing urinary copper excretion; it also prevents intestinal absorption of copper by
inducing metallothionein. Trientine is used at a starting dose of 20mg/kg per day in
children and adults, in divided doses, not to exceed 1500mg per day, with a main-
tenance dose of 15mg/kg also in divided doses, to be taken 1 h before or 2 h after
meals. Side effects include hemorrhagic gastritis, dysgeusia, sideroblastic anemia,
and rarely, hypersensitivity reactions and bone marrow suppression [70, 71].
Zinc acetate in children weighing less than 50kg is given at a dose of 25mg
three times a day. In others, including adults, the recommended dose is 50mg of
elemental zinc three times a day. Zinc should be taken on an empty stomach, at least
1 h before or 2–3 h after meals, and separated from beverages, other than water, by
at least 1 h [70, 71].
The use of DPA in pregnancy is accepted based on clinical experience [78]; how-
ever, zinc and trientine are also documented as safe [79, 80].
Maintenance doses are determined by measuring the excretion of copper in a
24-h urine collection, with a target of fewer than 0.6 micrograms per day [81].
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In patients who present with liver disease, not in acute liver failure, the initial
treatment is the pharmacological removal of copper from the blood and tissues and
to increase its excretion [70, 71]. Maintenance therapy aims to prevent copper accu-
mulation, which can be accomplished by the continuous use of DPA, and by the
administration of zinc salts. In this regard, zinc interferes with the absorption of
copper by inducing the synthesis of metallothionein in intestinal epithelial cells
leading to increased preferential binding of dietary copper to the latter in these
intestinal cells, which are shed subsequently as part of the rejuvenation process of
the intestine. Although zinc prevents further copper accumulation, its capability to
decopper is less than that of DPA, and thus, it does not mobilize copper from laden
tissues [82].
The course of disease in patients on treatment with oral chelators for WD was
examined retrospectively in a cohort study that included 405 patients, of whom 238
were women. Changes in medication were common, leading to the analysis of 471
chelator monotherapies, 326 on DPA, and 141 on trientine. Liver transplantation
was performed in 9 of the 326 (2.8%) patients treated with DPA, and in 3 of the 141
(2.2%) treated with trientine. Adverse events were signicantly more common in
the patients receiving DPA than in those receiving trientine. After 4 years of therapy,
4 patients from the 333 (1.2%) who had been treated with oral chelators experienced
worsening of liver function. Improvement of liver function was experienced by over
90% of patients. Eighty-eight of 143 patients (62%) exhibited neurological improve-
ment after 4 years of treatment, with 38% not demonstrating any benets, ndings
that may suggest that the neurological impairment was permanent. Of note, neuro-
logical deterioration was observed signicantly less frequently in patients given
DPA rst (6 of 295) than in those given trientine rst (4 of 38); P=0.018. These
ndings suggest that chelating agents are effective therapies for most patients with
WD [83].
Transient impairment of neurological function can be associated with the initial
treatment with DPA in 20% of the patients at the beginning of the chelation period,
which appears to be related to the copper bound to ceruloplasmin versus free cop-
per, which is what causes toxicity, and which, as a result of oral chelators, changes
in proportion, resulting in a relative increase of free copper. This idea is supported
by studies documenting an association between high free copper pool and neuro-
logical deterioration; specically, a study that included ve patients with WD and
who exhibited neurological worsening on trientine therapy over 8 weeks showed
signicant spikes in the concentration of free serum copper, in contrast to patients
who did not worsen, in whom no free copper spikes were documented [84].
Long-term zinc monotherapy in symptomatic patients with WD was studied in
17 subjects with a mean age of 18years, ranging from 13 to 26, whose clinical pre-
sentation was hepatic in 7, neurological in 5, and combined in another 5, followed
up on treatment for a median of 14years, with a range from 2 to 30. Zinc mono-
therapy was reported as good in patients with neurological complications; however,
in patients with cirrhosis, it did not prevent decompensation of liver disease [85].
These ndings contrast to those from a retrospective study in which 288 patients
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were followed for 17 years; it was documented that hepatic symptoms developed in
196 patients (68.1%) and neuropsychiatric in 99 (34.4%), with increased failure to
improve liver disease in zinc monotherapy, i.e., in 14 of 88 (16%) versus 4 of 313
(1.3%). The actuarial survival, without transplantation, was calculated to favor che-
lating agents as compared to zinc. These data suggested that chelating agents are
better than zinc in the prevention of deterioration of liver disease. Thus, monitoring
the clinical course to determine if changes in therapy should be made is recom-
mended for zinc managed patients with WD [86].
Patients diagnosed with WD should be started on chelating therapy. No studies
comparing DPA versus zinc are available; thus, the choice of therapy depends on the
clinician’s experience and the patient’s choice; however, monitoring the effect of
decoppering is required. Adequate decoppering may take 1–3 years to change to
maintenance therapy. On maintenance with DPA, the excretion of less than 0.6mg
per 24h off medication is a practice followed by some investigators [81]. Of note,
it is documented that 36% of children who have achieved acceptable decoppering
with DPA or zinc have increased serum activity of transaminases [87].
Thirty-one percent of patients have been reported to discontinue DPA because of
side effects, including nephrotoxicity, hematological abnormalities, and elastosis
perforans serpiginosa [83]. In this regard, tetrathiomolybdate, which acts by form-
ing a tripartite complex with copper and protein, preventing the absorption of
endogenously secreted and dietary copper, is being studied for the management of
WD and reported to be well tolerated versus trientine [88, 89].
Adherence to therapy is fundamental in managing patients with WD [90];
patients can regress to a copper-laden state and go into liver failure if the cessation
of treatment occurs [91]. Unaffected relatives without ndings of WD must also be
treated lifelong [70].
The follow-up of stable patients consists of physical examination, hemogram,
serum electrolytes, renal function, serum copper, and 24-h urine collection for cop-
per every 6 months. Bone marrow suppression tends to suggest overtreatment,
which required dose adjustment.
A considerable proportion of patients, i.e., 50.5% from a sample of 210 con-
tacted by mail or identied retrospectively, still reported neurological symptoms;
31.3% were treated with anticholinergics and botulinum toxin to treat dystonia, and
anticonvulsants to treat tremor [92].
Under maintenance therapy, the development of hepatic and neurological decom-
pensation, or recurrence of clinical ndings, including KF rings, suggest suboptimal
control of copper accumulation for which reassessment is required.
It is recommended that patients avoid foodstuff rich in copper, for which referral
to a nutritionist is encouraged.
The exclusion of WD in patients with liver disease is fundamental as the disease
is treatable and dreadful complications can be prevented with treatment.
The reader is referred to ClinicalTrials.gov to identify clinical trials in WD.
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Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is uncommon in WD.From a median follow-up of
15 years (range 0.1–51.2), a study that included 130 patients with WD documented
that two patients from the sample developed HCC, one in spite of appropriate
decoppering after 50years of diagnosis, and another with newly diagnosed WD.Of
the 74 patients with cirrhosis (57%), 64% compensated, and 36% decompensated,
20% improved, 46% remained stable, and 24% deteriorated, with no data presented
in 10%. The estimated annual risk for HCC was reported as 0.09% (95% condence
interval [CI]: 0.01–0.28), with analysis of cirrhotic patients documenting an annual
risk for HCC of 0.14% (95% CI: 0.02–0.46). The results of the meta-analysis were
reported to show an annual risk for HCC of 0.04% (95% CI: 0.01–0.10) and a mor-
tality rate of 2.6 per 10,000 person-years (95% CI: 0.7–7.0) [93]. These results
coincide with those of a retrospective review that included 1186 patients, 14 of
whom developed hepatobiliary malignancies including HCC in 8 and intrahepatic
cholangiocarcinoma in 6, with a calculated prevalence of 1.2% and an incidence of
0.28 per 1000 person-years. Of note, the analysis of the tumor did not show abnor-
mal copper concentration [94]. However, a retrospective study explored the inci-
dence of intraabdominal malignancies in patients with WD, in two specialty clinics
in the United Kingdom and Sweden. The study included 303 patients followed from
1955 to 2002. The frequency of HCC was 4.2% in patients followed between 10 and
19 years, 5.3% in patients followed between 20 and 29years, and 15% in patients
followed between 30 and 39years, with no tumors identied after 40years of fol-
low- up. The types of malignancies included HCC, cholangiocarcinoma, and poorly
differentiated adenocarcinomas of undetermined primary site. These authors did
support the idea of screening patients with WD for malignancies, i.e., intraabdomi-
nal malignancies. In regards to HCC, screening in patients with cirrhosis is an estab-
lished practice.
Liver Transplantation
The indication for liver transplantation in WD is decompensated liver disease and
acute liver failure, the latter mostly in children; however, liver transplantation in
patients with neuropsychiatric involvement is controversial.
A retrospective multicenter study from liver transplant centers in Italy that cov-
ered the period of 2006–2016 documented a proportion of 0.4% of transplants done
because of WD, comprised of 29 adult patients, 18 of whom were women, average
aged 29years, with a range from 19 to 60, with a median MELD score of 27, with
a range of 6–49 at the time of transplantation. Seventeen patients (63%) had decom-
pensated liver disease at the time of transplantation versus two (7%) who underwent
transplantation for neurological complications. The documented survival post pro-
cedure was 88% at 1 year, and 83% at ve, with the uncommon resolution of
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neuropsychiatric symptoms early post-transplant. These data were interpreted to
indicate a low number of liver transplantation for patients with WD in Italy; uncer-
tainty regarding the improvement of neuropsychiatric complications remains [95].
Long-term results from liver transplantation conducted in France from 1985 to
2009 for WD were documented in a retrospective review of 121 procedures, indicat-
ing that acute liver failure was a rare indication. Actuarial survival rates were 87%
at 5, 10, and 15years. The study group was comprised of 75 adult patients, with a
median age of 29years, a range from 18 to 66, and 46 children, with a median age
of 14 years, and a range from 7 to 17. The indications for liver transplantation were
fulminant liver failure in 64 (53%), with a median age of 16 years, range from 7 to
53, end-stage liver disease in 50 (41%), with a median age of 31.5years and a range
from 12 to 66, and severe neurological complications in seven (6%), with a median
age of 21.5years, and a range from 14 to 42, with a post transplantation follow-up
ranging from 0 to 23.5months, with a median of 72. The prognosis was worse in
patients transplanted for fulminant and subfulminant liver failure, nonelective, pre-
liver transplantation renal insufciency, and liver transplantation prior to 2000 than
liver transplantation for other indications. It was reported that there was improved
renal function with no patient having stage III kidney disease. The results were
interpreted to reect good outcomes post liver transplantation in patients with WD,
including those with renal insufciency [96].
The large European experience with liver transplantation in children with WD
was documented from a retrospective cohort study that included data from all
patients transplanted for WD and enrolled in the European Liver Transplant Registry
from January 1968 until December 2013. Three hundred and thirty-eight children,
57% of whom were girls, underwent LT at 80 different centers in Europe. The
median age at liver transplantation was 14 years (interquartile range [IQR],
11.2–16.1 years) with a median post-liver transplantation follow-up of 5.4years
(IQR, 1.0–10.9years). As documented in other studies, the survival rates were high,
reported as 87%, 84%, and 81% at 1, 5, and 10 years post liver transplantation,
respectively, with overall survival reported to have improved over the last decades
[46]. Similar good post-liver transplantation outcomes were reported in the pediat-
ric population [97]. A literature review from 1971 that concerned 290 patients docu-
mented that decompensated liver disease and acute liver failure were the main
indications for LT, with a 1-year survival of 91.9% and 88.2% at 5 years, with a
reported excellent quality of life. Retransplantation was done in 16 patients due to
graft rejection [97].
References
1. Wilson AAK.Progressive lenticular degeneration: a familial nervous disease associated with
cirrhosis of the liver. Brain. 1912;34:295–509.
2. Barbosa ER, Machado AA, Cancado EL, Deguti MM, Scaff M.Wilson’s disease: a case report
and a historical review. Arq Neuropsiquiatr. 2009 Jun;67(2B):539–43.
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