The document provides information on Wilson's disease, including: 1) Wilson's disease is an inherited disorder of copper metabolism caused by mutations in the ATP7B gene. This leads to copper accumulation in the liver, brain, kidney, and cornea. 2) Clinical presentations can include hepatic (e.g. cirrhosis), neurological (e.g. movement disorders), psychiatric, and ocular features like Kayser-Fleischer rings. 3) Diagnosis involves low serum ceruloplasmin, elevated urinary copper, genetic testing, and liver biopsy. Treatment involves chelation therapy and sometimes liver transplantation for severe cases.

1. WILSON’S DISEASE
Dr Sagar P kabadi
MBBS MD (Gen Medicine) Fellowship In therapeutic Endoscopy
BGS Global Hospitals, Dept Of Medical Gastroenterology,Bangalore

2. History
 The disease bears the name of the British physician Samuel
Alexander Kinnier Wilson (1878–1937), a neurologist who
described the condition, including the pathological changes in the
brain and liver, in 1912.
 Kinnear Wilson first described Wilson’s Disease as a progressive,
lethal neurologic dysfunction with liver cirrhosis and a corneal
abnormality, the Kayser-Fleischer(KF) rings.
 In this disease, inadequate hepatic copper excretion leads to copper
accumulation in the liver, brain, kidney and cornea.

3.  Copper, a component of several essential enzymes, is toxic to cells when present in excess.
 Dietary intake of copper generally exceeds the required physiological amount, and hence
mechanisms to control influx and efflux from cells must maintain an appropriate balance.
 The body contains 110 mg of Cu, predominantly in the muscles (28 mg), bones (46 mg),
and connective tissues.The Cu pool in the musculoskeletal system is in constant exchange
with plasma.
 Plasma contains approximately 1 mcg/mL of cu, of which 60–95% is bound to
ceruloplasmin. Ceruloplasmin is a source of Cu for peripheral organs, where Cu is an
essential cofactor for many enzymes.
 Normal dietary Cu intake is 1.5–5 mg in 24 h, 50–60% of which is unabsorbed and
excreted in feces; 25–40% is absorbed from the duodenum, stored by enterocytes and
bound to metallothioneins in a nontoxic form.
 From this intestinal pool, 75% flows through the portal system with albumin or
transcuprein and is taken up by the liver. The remaining 25% is bound to albumin in the
circulation.

4.  20% of Cu is re-excreted back into the gastrointestinal tract through bile and
80% is transported to the periphery, bound to ceruloplasmin.
 The biliary excretion is approximately 2.5 mg/d. Near-similar amounts are
excreted from other secretions (saliva, gastric, pancreatic, and intestinal fluid).
Two human disorders of copper transport are known :
i.e Menkes Disease - a X linked defect in transport of copper from the the
intestine that leads to copper deficiency,
Other is Wilson’s Disease, an autosomal recessive disorder of copper overload.

5. Epidemiology
 Estimated prevalence in most population is about 1 in 30,000
 One of the highest prevalence ever noted was from a small island called
Crete, Greece.
 Men and women, are equally affected by this disease, though women are
more likely than men to develop acute Liver Failure due to Wilson’s
Disease.

6. Copper Metabolism
 Dietary copper is absorbed in the upper intestine, it is loosely bound to albumin
& histidine, and is transported to variety of tissues.
 Portal blood flow directs most copper to liver.
 Trace amounts of copper are required for essential enzymes that affect
• Connective tissue & elastin cross-linking (Lysyl oxisade)
• Free radical scavenging ( superoxide dismutase)
• Electron transfer ( cytochrome oxisade)
• Pigment production ( Tyrosinase)
• Neurotransmission ( dopamine β-mono-oxygenase)

7.  Molecular copper is never free within a cell.
 Copper in hepatocytes & other cells are bound to metalochaperones, &
low molecular weight proteins that specifically deliver copper to target
molecule.
 In the liver, copper is incorporated to apoceruloplasmin to produce
ceruloplasmin. More than 90% of copper in plasma is an integral part of
ceruloplasmin, an α2 glycoprotein that contains 6 molecules of copper &
has a molecular weight of 132kd.

9.  Normal Serum concentration of ceruloplasmin in adults, as measured by
immunochemical or enzymatic techniques, is 200-400mg/L,
Rising from a very low level at birth to 300-500mg/L in first years of life.
 Because it is an acute phase reactant, ceruloplasmin is elevated by
- Inflammation ( including inflammatory hepatic disease)
- Pregnancy, and use of exogenous estrogen
 Majority of ingested copper is excreted by bile, a very small excretion occurs
through urine.

10. Genetics
 Wilson’s Disease(WD) is caused by mutations to the gene coding for ATPase copper
transporting beta polypeptide (ATPase 7B), which is located in chromosome 13.
 ATP7B is relatively a large gene at around 80kb, and it contains 21 exons.
 A variety of mutations(over 300) have been identified in in ATP7B gene of WD patients, that
include insertion, deletion, splice site and point mutations.
 Frame shift deletions and nonsense mutations that cause a truncation of translated protein
product usually result in severe form of disease because of loss of functional protein.

11. Model of a hepatocyte showing major proteins in the copper transport pathway. Low-molecular-weight copper
chaperones (ATOX1, COX17, and CCS) deliver copper to specific target proteins (ATP7B, cytochrome oxidase,
and superoxide dismutase, respectively). SCO1 transports copper across the mitochondrial membrane. ATP7B
(shown as a channel) traffics from the trans-Golgi network (TGN) to cytoplasmic vesicles that deliver copper to
the bile canaliculus. COMMD1 may be involved in excretion of copper into bile.

12.  The Wilson ATPase(ATP7B) has at atleast 2 intercellular functions :
- Participating in synthesis of enzymatically active ceruloplasmin & Expediting biliary
excretion of copper.
 It is localized in trans-golgi network & traffiks to cytoplasmic vesicles in presence of
increased copper.
 When intracellular concentrations of copper are elevated, Wilson ATPase is found near
apical (bile cannicular) membrane in hepatocytes, consistent with its proposed function of
facilitating excretion of copper via bile.

13.  Additional proteins are involved in intracellular disposition of copper.
Loosely bound to intracellular metallochaperones ( also called copper
chaperones), copper is transported to specific proteins, such as superoxide
dismutase in cytoplasm & various copper-containing proteins in
mitochondria.
 The metallochaperone antioxidant 1 copper chaperone (ATOX1) transports
copper to the Wilson ATPase.

14.  H1069Q and R778L mutation is one of the most commonest mutations with an allelic frequency
of 10 to 40 percent.

15. Pathology
 Histologic findings in liver – include liver steatosis, focal necrosis, glycogenated
nuclei in hepatocytes and sometime apoptotic bodies.
 As parenchymal changes progresses, through repeated episodes of lobular
necrosis, peri-portal fibrosis occurs.
 Later when cirrhosis occurs, It is usually macro-nodular.

16. Early in the course of Wilson disease, hepatocellular copper is bound mainly to metallothionein and is distributed diffusely in the
cytoplasm of hepatocytes; therefore histochemical stains for copper are negative. As the disease progresses, the copper content
exceeds the storage capacity of metallothionein, and copper is deposited in lysosomes. Lyosomal aggregates of copper can be
detected by special staining techniques for copper or copper-binding protein (such as rubeanic acid or orcein, respectively). In
the cirrhotic liver, some areas may have no stainable copper at all.
If the clinical presentation mimics autoimmune hepatitis, a liver biopsy specimen may reveal classic histologic features such as
interface hepatitis. Inflammation may be severe. Mallory (Mallory-Denk) bodies may be found. In patients who present with
fulminant hepatic failure, histologic findings confirm pre-existing liver disease; cirrhosis may be present; and parenchymal
copper is located mainly in Kupffer cells rather than hepatocytes.

17. *Richard K Gilroy, MBBS, FRACP Associate Professor, Medical Director of Liver Transplantation and Hepatology,
Department of Internal Medicine, Kansas University Medical Center

18. Clinical Features
 Hepatic Presentation
 Neurologic Presentation
 Psychiatric presentation
 Ocular
 & other system involvement.

19. Hepatic Presentation
 Hepatic presentation more common in younger patients than older, and WD diagnosis must be
considered as a possible diagnosis in any child, symptomatic or not, with hepatomegaly,
persistently elevated aminotransferases levels, or evidence of fatty liver.
 Symptoms maybe vague & non-specific, such as fatigue, anorexia or abdominal pain.
 Occasionally patients present with self-limited clinical illness that resembles acute hepatitis
with malaise, anorexia, nausea, jaundice, elevated aminotransferase and abnormal coagulation
tests, also some may have unexplained hemolysis.
 Or some may have well established chronic liver disease with hepato-splenomegaly, ascites,
congestive splenomegaly, low serum albumin and abnormal coagulation tests

20.  WD maybe indistinguishable from AIH. As in AIH, onset maybe acute.
Fatigue, malaise, arthropathy rashes may occur, lab findings may suggest elevated
aminotransferases levels, greatly increased serum IgG levels, and detectable non-specific
autoantibodies, such ANA & ASMA.
 WD must be specifically ruled out because the treatment of the 2 disease are entirely different.
 In contrast to ALF, a fulminant hepatic failure is typically characterized by disproportionately
low aminotransferases levels at the onset of clinically onset of disease.

21.  In adults who present with Wilsonian fulminant liver failure, the combination
of a ratio of the alkaline phosphatase level to the total bilirubin level of less
than 4 and a ratio of the aspartate aminotransferase (AST) to alanine
aminotransferase (ALT) level of greater than 2.2 can be extremely helpful for
making the diagnosis.
 These patients may require urgent Liver transplantation, because they do not
respond to chelation therapy, albumin dialysis and related techniques may serve
as temporary measures until liver transplantation can be performed.

22. Neurologic Presentation
 It can occur in 2nd or 3rd decades but has been reported in children as young as 6-10
years of age.
 Most patients with a neurologic presentation have hepatic involvement.
 Neurologic presentation has 2 main patterns : Movement disorders and dystonia
 Movement disorders occur early – in the form of tremors, poor co-ordination, and
loss of fine motor control.
 Spastic disorders which occur later include dysarthria, drooling, and swallowing
difficulty.
 Seizures are uncommon , and intellect is unaffected.
 MRI is the most sensitive imaging to evaluate further.

23. Psychiatric Presentation
 As many as 20% of patients may present with purely psychiatric symptoms.
 These symptoms are highly variable, although depression is common.
 Phobias & compulsive behaviours have been reported, aggressive or anti-social
behavior may also be found.

24. Ocular Presentations
 Classic Kayser-Fleischer ring is caused by copper
deposition in Descemet’s membrane of cornea, they
occur because fluid-streaming favours accumulation
near the limbus, especially at superior & inferior
poles, and eventually circumferentially around iris.
 KF rings are visible on direct inspection only when
iris pigmentation is light and copper deposition is
heavy, careful slit-lamp examination is mandatory.

25.  KF rings maybe absent in 40-60% of patients with exclusive hepatic
involvement & in pre-symptomatic patients.
 Most patients with Neuro-psyhchiatric involvement have KF rings, only 5%
do not.
 KF rings is not specific for wilsons disease, it can also be seen in patients with
prominent cholestatic component, such as PSC, PBC or familial cholestatic
syndromes.

27. Involvement of other systems
 Episodes of hemolytic anemia can result from sudden release of copper into the blood.
 Renal disease, mainly fanconi’s syndrome, maybe prominent.
 Nephrolithiasis, Arthritis, musculo-skeletal pains, osteoporosis & osteo-chondritis dessicans may also
be associated.
 Copper deposition in muscles may cause rhabdomylosis, in heart it can lead to cardiomyopathy &
arrythrymias
 Ammenorhea, testicular pathology, infertility, spontaneous abortions can also occur
 Rarely, pancreatitis can also occur due to deposition of copper in pancreas.

28. Approach to Diagnosis
 Classic patient with WD, whether displaying hepatic or neurological findings, maybe
considered to be someone between 6-40years of age, with serum ceruloplasmin levels
<5mg/dl & definite KF rings.
 Age is no longer diagnostic criteria.
 Presence of CLD or typical neurological symptoms, also low serum ceruloplasmin levels &
elevated basal 24-hour copper excretion is highly suggestive of WD.
 Measurement of 24-hour urinary copper excretion after administration of d-penicillanmine
maybe definitive
 Typical ocular findings complete clinical findings but are not essential.

29.  Percutaneous Liver Biopsy is useful in assessing severity of liver disease, but it may have
to be delayed in patients with severe liver dysfunction
 Ultimately molecular genetic analysis is the only convincing and reliable diagnostic
procedures.
 Mutation analysis is done by high-throughput sequencing of either selected or all exons of
gene, supplemented by sequencing of promoter region, close examination of exon/intron
boundaries, & exclusion of large deletions by multiplex ligation – dependent probe
amplification(MLDA) technology.

30. Pre-symptomatic Diagnosis off First-degree relatives
 In the absence of genetic analysis, screening should include physical
examination, liver biochemical tests, serum copper & ceruloplasmin levels,
basal 24hr urinary copper levels and careful slit-lamp examination.
 Children >6years of age who appear unaffected, must be screened at regular
intervals.

31.  Genetic screening by flanking markers, or by direct mutation analysis, is the most
reliable way to identify an affected 1st degree relative when patients DNA is
available for mutation analysis.
 The most useful genetic markers are stretches of di-nucleotides or tri-nucloetides
that show extensive variability in normal population, so that parents within
anyone family will carry different alleles of these markers.
 For deceased patients, tissue from autopsy or biopsy material can be used

32. Biochemical parameters in WD

33.  While a diagnosis is made by low serum ceruloplasmin levels, KF rings,
and elevated urinary copper excretion, additional tests maybe required to
treat patients with intermediate results.
 Such as MRI brain and Liver biopsy.
 Genetic testing also has a role in diagnosis of WD, but because of large
number of mutations seen in WD, it is generally reserved for those in
whom diagnosis cannot be made in anyother testing modalities, or to
screen family members when the mutation in ATP7B in the proband is
unknown.

34. Leipzig Classification for Wilson’s Disease

35. In 2006, Nazer's score (serum bilirubin, international normalized ratio(INR), and serum
albumin) was modified to add 2 parameters (AST and white blood cell count) to the score and
renamed it as New Wilson's Index (NWI).
An NWI score was associated with non-survival without liver transplantation. In a study from
South India, NWI and Pediatric End-Stage Liver Disease/Model for End-Stage Liver Disease
(MELD) were found to have modest accuracy in predicting outcomes in WD
Wilson’s Disease: Clinical Practice Guidelines of the Indian National Association for Study of the Liver, the Indian Society of Pediatric Gastroenterology, Hepatology
and Nutrition, and the Movement Disorders Society of India ; Aabha Nagral* ,y , Moinak S. Sarma z et al

36. MRI BRAIN –
showing hyperintensities in bilateral basal ganglia, thalamic region by T2
weighted images

37. *Mazumder MW1, Karim MB, Rukunuzzaman M. Et al

39. Treatment
 Once the diagnosis is confirmed, starting treatment early is critical and better
is the outcome.
 Patient should eliminate copper-rich foods such as organ meats, shellfish, nuts,
chocolate & mushrooms
 Main stay of treatment is by 3 drugs
1. D-penicillamine
2. Trientine
3. Zinc sulphate

40. D-penicillamine
 Is a sulfhydryl containing amino acid cysteine substituted with 2 methyl groups,
greatly increases urinary excretion of copper.
 Neurological symptoms may worsen initially after treatment with d-
penicillamine, most but not all recover with its continued usage.
 Substituting trientine or zinc reduces the risk. A febrile reaction with rash and
proteinuria develops in some patients within 7-10 days of beginning treatment.
Although treatment with d-penicillamine can be re-started again with
glucocorticoids, changing to alternative chelator is preferred.

41.  Adverse reactions include : the skin include various types of rashes,
pemphigus, and elastosis perforans serpiginosa. Hypothyroidism has been
reported. Other side effects vary from minor (loss of taste, gastrointestinal
upset, and arthralgias) to severe (proteinuria, leukopenia, or
thrombocytopenia).
 Aplastic anemia occurs rarely and does not always reverse when
penicillamine is stopped
 Nephrotic syndrome, Goodpasture’s syndrome, a myasthenia syndrome, and
a systemic disease that resembles systemic lupus erythematosus have all been
reported

42.  These severe side effects require immediate discontinuation of penicillamine and use of a
different chelator. Whether lifelong treatment with penicillamine is free of adverse
consequences is not yet clear.
 Patients who have taken penicillamine for 30 to 40 years may have chronic skin changes
with loss of elastic tissue.
 Whether the antifibrotic effect weakens other connective tissues is not known.
 Theoretically, chronic depletion of other trace metals may occur. In view of these side
effects, penicillamine should be used in the lowest effective dose

43.  Concomittant use of NSAIDs and other nephrotoxic drugs may increase the
risk of renal damage.
 Pyridoxine 25mg must be supplemented, since penicallamine increases the
requirement of vitamin b6.

44. Trientine
 Or Triethylene tetramine dihydrochloride – 2nd line of treatment.
 Trientine differs chemically from d-penicillamine in lacking sulfyhydrl groups.
Copper is chelated by forming a stable complex with the four constituent nitrogens in a planar
ring. Trientine increases urinarycopper excretion and may interfere with intestinal absorption.
Trientine is a less potent chelator than penicillamine, but the difference is not clinically
important.
Trientine produces little significant toxicity in patients with Wilson disease—apart from causing
occasional gastritis and inducing iron deficiency, apparently by chelating dietary iron. Trientine
is highly effective, even in patients with advanced liver fibrosis or as initial treatment in children.

45. Oral Zinc
 Mechanism of action is entirely different from that of the chelators.
 In pharmacologic doses, zinc interferes with the absorption of copper from the
gastrointestinal tract and increases the excretion of copper in the stool. The postulated
mechanism of action is through the induction of metallothionein in enterocytes.
 The metallothionein has a greater affinity for copper than for zinc and preferentially binds
copper from the intestinal contents.
 Once bound, the copper is not absorbed but is lost in the feces as enterocytes are shed during
normal turnover.
 Additionally, zinc may interfere with lipid peroxidation and enhance the availability of
glutathione.

46.  Problems with zinc therapy include gastritis, which is a common side effect, and
uncertainty about dosing.
 Using a zinc salt other than zinc sulfate may minimize gastritis; any zinc salt is equally
acceptable for the treatment of Wilson disease.
 Food interferes with the effectiveness of zinc, and some investigators recommend that no
food be eaten for one hour before or after a dose of zinc is taken

47.  Ammonium tetrathiomolybdate may be especially suitable for treatment of
severe neurologic Wilson disease because, unlike penicillamine, it is not
associated with early neurologic deterioration. Tetrathiomolybdate interferes
with the absorption of copper from the intestine and binds to plasma copper
with high affinity.
 Antioxidants may be a useful adjunct for preventing tissue damage.
 For pregnant patients with Wilson disease, treatment must be continued
throughout pregnancy. Postpartum hepatic decompensation is a risk if treatment
is stopped completely during pregnancy. Although many successful pregnancies
have occurred during treatment with penicillamine, the drug is officially
classified as a teratogen, trientine is a safer alternative

49. Consensus Statements on Treatment of WD Drug Therapy
 1. A chelating agent should be used for symptomatic patients with hepatic WD. DP is preferred
because of easy availability, cost, and efficacy
 2. Pre-symptomatic patients/those with hepatic disease on maintenance therapy/symptomatic
patients with neuroWD can be treated with zinc or chelating agent
 3. Lifelong treatment is necessary unless the patient has had a liver
 4. MARS and TPE can be offered to patients with ALF especially in the presence of
encephalopathy and is a good bridge therapy to LT, should the patient not show prompt
recovery
 5. DP is an effective chelator although associated with several side effects

50. Total Plasma Exchange / Dialysis
 Wilsonian crisis (hemolytic crisis and acute liver failure [ALF] in Wilson’s disease) is fatal and
almost all patients ultimately need a timely liver transplantation to save their lives.
 * A case report of a 7 year old boy, with Severe hemolysis and impending ALF that made a
rapid recovery with prompt initiation of plasmapheresis combined with continuous plasma
filtration adsorption (CPFA) and chelation therapy. Rapidly efficient removal of copper,
bilirubin, and albumin-binding toxins by hybrid blood purification alleviated hemolysis and
liver injury and successfully bridged the patient over the critical period to late liver
transplantation. Moreover, a review of the literature was performed examining the use of
plasmapheresis, molecular adsorbent recirculation system, single-pass albumin dialysis,
Combined with Continuous Plasma Filtration Adsorption Rescues Severe Acute Liver Failure
in Wilson’s Disease before Liver Transplantation
* Continuous veno-venous hemodiafiltration in Wilson disease (KARGER) 2019, Vol.47, No. 1-3

51.  SPAD is a form of albumin dialysis which utilizes a standard continuous hemodialysis system
with the addition of albumin to a standard dialysate. The albumin-containing dialysate allows
for improved clearance of protein-bound substances like non-ceruloplasmin-bound copper,
which is elevated in Wilsonian liver failure.
 It is one of four methods available to provide extracorporeal liver support, the others being
MARS, the Prometheus dialysis system, and PLEX combined with hemodialysis. While the
utility of MARS and the Prometheus dialysis system requires the added cost of purchasing
specific new equipment and staff training, SPAD is not difficult to set up and does not require
special filters/adsorbers or specific new equipment. Several case reports have reported the
efficacy of using SPAD as supportive treatment to successfully bridge patients with fulminant
Wilsonian liver failure to liver transplantation.
*Single Pass Albumin Dialysis and Plasma Exchange for Copper Toxicity in Acute Wilson Disease Bakhsh S.a,b · Teoh C.W.a,c · Harvey E.A.a,c · Noone
D.G.a,c

52. *Saudi Journal Of Liver/kidney transplantation 2018

53.  Unlike MARS, where the albumin solution is regenerated by removing protein-bound
substances through an activated charcoal column and an anion exchange resin, the albumin
dialysate in SPAD is discarded after a single pass, necessitating a large supply of albumin.
One strategy to conserve albumin and limit the cost of SPAD would be to reduce the
clearance, and the slower dialysate flow rates may improve dissociation of copper off
binding sites and across the membrane. Although the MARS has been used successfully to
bridge patients with WD to liver transplantation, analysis of the albumin dialysate in one of
the patients reported on by Sen et al. suggested that the MARS was saturated with copper
after the initial few hours, with no significant copper removal thereafter, presumably as there
is no cation exchanger in the circuit, potentially limiting its effectiveness for the treatment of
copper-related hemolysis.
 In contrast, SPAD has a potential advantage based on continuous removal of copper without
saturation of the albumin-binding capacity. Patients in this study, SPAD with a 4.5% (45 g/L)
albumin dialysate reduced serum copper levels by 28.7% and stabilized hemolysis and
multiorgan failure, bridging to a successful liver transplantation.
*Single Pass Albumin Dialysis and Plasma Exchange for Copper Toxicity in Acute Wilson Disease Sen ,Bakhsh S.a,b · Teoh C.W.a,c · Harvey E.A.a,c · Noone D.G.a,c

54.  PLEX is useful for removing protein-bound substances that are poorly removed via
conventional dialysis. An added advantage in this clinical situation is the replenishment of
coagulation factors with plasma replacement. The efficacy of PLEX in removing excess
copper in patients with fulminant WD has been illustrated in several case reports .Also in
another study serum copper levels were reduced by 47% after the first PLEX, confirming its
efficacy.
 However, significant acute kidney injury in a hemodynamically unstable child necessitated
the initiation of continuous renal replacement therapy, which influenced our decision to add
SPAD to effect a more sustained reduction in serum copper levels. In combination, a sustained
54.4% reduction of serum copper levels was achieved, together with stabilization of
hemolysis, bilirubin levels, and multiorgan failure for 4 days, bridging the patient to a
successful liver transplantation. As the patient also had a concomitant acute kidney injury, the
addition of SPAD allowed for an improvement of his fluid and acid-base management.
* Hilal T, Morehead RS. Fulminant Wilson’s Disease Managed with Plasmapheresis as a Bridge to Liver Transplant. Case Rep Med.
2014;2014:672985

55.  The clinical utility of SPAD alone and SPAD in combination with PLEX as potentially effective
measures to reduce serum copper levels, stabilize hemolysis, and improve the clinical status of
patients with fulminant WD as a bridge to liver transplantation; however, further clinical studies are
needed to confirm its efficacy. PLEX is widely available and effective in reducing serum copper
levels. However, rebound rises in serum copper levels between exchanges can occur. The addition of
SPAD may prevent such rebound and has the added advantage of removing small-molecular-weight
solutes that cause hepatic coma, managing fluid overload, and correcting electrolyte and acid-base
abnormalities .
* Hilal T, Morehead RS. Fulminant Wilson’s Disease Managed with Plasmapheresis as a Bridge to Liver Transplant. Case Rep Med. 2014;2014:672985

56. Indications for Liver Transplantation
 1. Patients with fulminant presentation with hepatic encephalopathy or hemolytic crisis
 2. New Wilson's Index has been used as a predictor of LT (for both acute or chronic
presentation). Rising bilirubin, advanced hepatic encephalopathy, and acute hemolysis have
been suggested as better predictors for LT and need validation
 3. Living donor liver transplant from heterozygous sibling is effective and safe for both donor
and recipient
 4. Liver transplantation is not indicated for isolated severe neurological WD. When the liver is
also diseased, the decision should be individualized because significant neurological disease is
a predictor of poor outcome
* Consensus statements on treatment of WD 2018

57. Prognosis
 Patients with early hepatic disease have a generally favorable prognosis as long as treatment
is consistent and well tolerated.
 Fulminant Hepatic failure necessitates LT.
 Outcome is favorable with 1 year survival rates of 80-90%.
 Patients with neuro-psychiatric manifestations have poorer outcomes after LT and adhere
poorly to medical regimens, therefore LT must be reserved for patients who present with
severe DCLD that is unresponsive to therapy or with fulminant hepatic failure.
 Quality of life in WD patients maybe compromised because of drug toxicity, deficiencies of
trace elements may occur with any chelation therapy, but its clinical importance varies.

59. References
 Sleisenger book of Gastroenterology 10th edition
 *Richard K Gilroy, MBBS, FRACP Associate Professor, Medical Director of Liver
Transplantation and Hepatology, Department of Internal Medicine, Kansas University Medical
Center
 *Mazumder MW1, Karim MB, Rukunuzzaman M. Et al
 Plasmapheresis Combined with Continuous Plasma Filtration Adsorption Rescues Severe
Acute Liver Failure in Wilson’s Disease before Liver Transplantation Zhang Y. · Li L. · Zhang
X. · Xu W. · Guo Q. · Zhou J. Author affiliations Blood Purif 2019;47:120–125 and continuous
veno-venous hemodiafiltration in Wilson disease (KARGER) 2019, Vol.47, No. 1-3
 Journal of Clinical and Experimental Hepatology | January/February 2019 | Vol. 9 | No. 1 | 74–98

60.  *Single Pass Albumin Dialysis and Plasma Exchange for Copper Toxicity in Acute Wilson
Disease Bakhsh S.a,b · Teoh C.W.a,c · Harvey E.A.a,c · Noone D.G.a,c
 AASLD guidelines 2018
 JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY
 Wilson’s Disease: Clinical Practice Guidelines of the Indian National Association for Study of
the Liver, the Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition, and the
Movement Disorders Society of India ; Aabha Nagral* ,y , Moinak S. Sarma z et al

61. THANKYOU 