Acute Liver Failure
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Acute Liver Failure
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Amanita phalloides
O (Latin for ‘phallic
toadstool’; also known as
the ‘death cap’) is a lethal
cause of jaundice.
O It is the most toxic
mushroom known.
O After ingestion (its benign
appearance is confusing),
amatoxins induce hepatic
necrosis
O leaving few options other
than transplantation.
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Clinical assessment
O Cerebral disturbance (hepatic encephalopathy and/or cerebral
oedema) is the cardinal manifestation of acute liver failure,
O but in the early stages this can be mild and episodic,
O and so its absence does not exclude a significant acute liver injury
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As the liver fails, nitrogenous waste (as ammonia) builds up in the
circulation and passes to the brain, where astrocytes clear it (by
processes involving the conversion of glutamate to glutamine).
This excess glutamine causes an osmotic imbalance and a shift of fluid
into these cells—hence cerebral oedema.
What else could be clouding consciousness?
Hypoglycaemia; sepsis; trauma; postictal
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Clinical assessment
O Cerebral oedema may occur due to increased intracranial
pressure,
O causing unequal or abnormally reacting pupils, fixed pupils,
O hypertensive episodes, bradycardia,
O hyperventilation, profuse sweating,
O local or general myoclonus,
O focal fits or decerebrate posturing.
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Clinical assessment
O Papilloedema - rare and is a late
sign.
O More general symptoms -
weakness,nausea and vomiting.
O Right hypochondrial discomfort
- occasional feature.
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Clinical assessment
O Patient may be jaundiced
O but jaundice may not be present at the outset (e.g. in
paracetamol overdose),
O and there are a number of exceptions, including Reye’s syndrome,
in which jaundice is rare.
O Occasionally, death may occur in fulminant cases of acute liver
failure before jaundice develops.
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Clinical assessment
O Fetor hepaticus (a distinctive
‘mousy’ odour of dimethyl
sulphide on the breath, which is
evidence of portosystemic
shunting (with or without
encephalopathy)) can be present.
O Asterixis/flap (a coarse flapping
tremor when the arms are
outstretched and hands dorsiflexed)
O Constructional apraxia (difficulty
drawing a figure) (cannot copy a 5
pointed star?)
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Flapping tremor.
O Jerky forward movements every
5–10 secs,
O when arms are outstretched and
hands are dorsiflexed,
O suggest hepatic encephalopathy.
O The movements are coarser than
those seen in tremor.
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Number connection test
O These 25 numbered circles can
normally be joined together
within 30 secs.
O Serial observations may provide
useful information, as long as the
position of the numbers is varied
to avoid the patient learning their
pattern.
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Clinical assessment
O The liver is usually of normal size, later smaller.
O Hepatomegaly is unusual and
O In the presence of a sudden onset of ascites, suggests
venous outflow obstruction as the cause (Budd–Chiari
syndrome).
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Clinical assessment
O Splenomegaly is uncommon and never prominent.
O Ascites and oedema are late developments and may be a
consequence of fluid therapy.
O Other features are related to the development of complications
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Complications of acute liver
failure
O Encephalopathy and cerebral oedema
O Hypoglycaemia
O Metabolic acidosis
O Infection (bacterial, fungal)
O Renal failure
O Gastrointestinal bleeding
O Multi-organ failure
(hypotension and respiratory failure)
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Investigations to determine the
cause of acute liver failure
O Toxicology screen of blood and urine
O HBsAg, IgM anti-HBc
O IgM anti-HAV, Anti-HEV
O HCV, cytomegalovirus, herpes simplex, Epstein–Barr virus
O Caeruloplasmin, serum copper, urinary copper, slit-lamp eye
examination
O Autoantibodies: ANA, ASMA, LKM, SLA
O Immunoglobulins
O Ultrasound of liver and Doppler of hepatic veins
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Investigations to determine the
cause of acute liver failure
O (ANA = antinuclear antibody;
O anti-HBc = antibody to hepatitis B core antigen;
O ASMA = anti-smooth muscle antibody;
O HAV = hepatitis A virus;
O HBsAg =hepatitis B surface antigen; HCV = hepatitis C
virus; HEV = hepatitis E virus;
O IgM= immunoglobulin M;
O LKM = liver–kidney microsomal antibody;
O SLA = solubleliver antigen)
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Suggested management of abnormal
LFTs in asymptomatic patients
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Suggested management of abnormal
LFTs in asymptomatic patients
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Investigations
O Plasma aminotransferase activity is particularly high after
paracetamol overdose, reaching 100–500 times normal,
O but falls as liver damage progresses and
O is not helpful in determining prognosis
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Investigations
O Plasma albumin remains normal unless the course is
prolonged.
O Percutaneous liver biopsy is contraindicated because of the
severe coagulopathy,
O but biopsy can be undertaken using the transjugular route if
appropriate.
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Investigations
Neuro physiology:
O EEG,
O evoked potentials (and neuroimaging) have a limited
role.
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Adverse prognostic criteria in
acute liver failure*
Paracetamol overdose
• H+ > 50 nmol/L (pH < 7.3) at or beyond 24 hours following the
overdose
Or
• Serum creatinine > 300 μmol/L (≅ 3.38 mg/dL)
O plus prothrombin time > 100 secs
O plus encephalopathy grade 3 or 4
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Adverse prognostic criteria in
acute liver failure*
Non-paracetamol cases
• Prothrombin time > 100 secs
Or
• Any three of the following:
O Jaundice to encephalopathy time > 7 days
O Age < 10 or > 40 years
O Indeterminate or drug-induced causes
O Bilirubin > 300 μmol/L (≅ 17.6 mg/dL)
O Prothrombin time > 50 secs
Or
• Factor V level < 15% and encephalopathy grade 3 or 4
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Adverse prognostic criteria in
acute liver failure*
O *Predict a mortality rate of ≥ 90% and
O are an indication for referral for possible liver transplantation.
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Management
O Patients should be managed in a specialized unit.
O Transfer criteria to specialized units for patients
with acute liver injury
• INR >3.0
• Presence of hepatic encephalopathy
• Hypotension after resuscitation with fluid
• Metabolic acidosis
• Prothrombin time (seconds) > interval (hours) from
overdose (paracetamol cases)
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Management: ALF
O Nurse with a 20° head-up tilt in ITU.
O Protect the airway with intubation
O Insert an NG tube to avoid aspiration and remove any
blood from stomach.
O Insert urinary and central venous catheters to help
assess fluid status.
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Monitoring in acute liver failure
Cardiorespiratory
O Pulse
O Blood pressure
O Central venous pressure
O Respiratory rate
Neurological
O Intracranial pressure monitoring (specialist units)
O Conscious level
Fluid balance
O Hourly output (urine, vomiting, diarrhoea)
O Input: oral, intravenous
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O Daily weights
Monitoring in acute liver failure
Blood analyses
O Arterial blood gases
O Peripheral blood count (including platelets)
O Sodium, potassium, HCO3−, calcium, magnesium
O Creatinine, urea
O Glucose (2-hourly in acute phase)
O Prothrombin time
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Monitoring in acute liver failure
Infection surveillance
O Cultures: blood, urine, throat, sputum, cannula sites
O Chest X-ray
O Temperature
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Management: ALF
O 10% glucose IV, 1L/12h to avoid hypoglycaemia. Do blood
glucose every 1–4h.
O Treat the cause, if known (eg GI bleeds, sepsis, paracetamol
poisoning)
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Management: ALF
O If malnourished, get dietary help: good nutrition can decrease
mortality.
O Give thiamine and folate supplements
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Wernicke’s encephalopathy
O Thiamine (vitamin B1) deficiency with a classical triad of
O 1 confusion 2 ataxia and 3 ophthalmoplegia (nystagmus,
lateral rectus, or conjugate gaze palsies).
O inadequate dietary intake, ↓GI absorption, and impaired
utilization of thiamine resulting in focal areas of brain
damage, including periaqueductal punctate haemorrhages
(mechanism unclear).
O Always consider this diagnosis in alcoholics:
O it may also present with memory disturbance, hypotension,
hypothermia, or reduced consciousness
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Wernicke’s encephalopathy
O Diagnosis: Primarily clinical. Red cell transketolase activity
↓(rarely done).
O Treatment: Urgent replacement to prevent irreversible Korsakoff ’s
syndrome
O Give thiamine (Pabrinex®), 2 pairs of high potency ampoules
IV/IM/8h over 30min for 2d, then 1 pair OD for a further 5d.
O Oral supplementation (100mg OD) should continue until no longer
‘at risk’ (+ give other B vitamins). Anaphylaxis is rare.
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Wernicke’s encephalopathy
O If there is coexisting hypoglycaemia, make sure thiamine is
given before glucose,
O as Wernicke’s can be precipitated by glucose administration to a
thiamine-deficient patient
O Prognosis:
O Untreated, death occurs in 20%, and Korsakoff ’s psychosis
occurs in 85%
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Korsakoff ’s syndrome
O Hypothalamic damage & cerebral atrophy due to thiamine
(vitamin B1) deficiency (eg in alcoholics).
O May accompany Wernicke’s encephalopathy.
O There is ↓ability to acquire new memories, confabulation
(invented memory, owing to retrograde amnesia), lack of insight
& apathy.
O Rx: See Wernicke’s
O Rarely recover.
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Management: ALF
O Treat seizures with phenytoin (p826).
O Phenytoin infusion: 15–18mg/kg IVI (roughly 1g if 60kg, and 1 .
5g if 80kg; max 2g),
O at a maximum rate of 50mg/min (don’t put diazepam in same
line: they don’t mix).
O Beware ↓BP and do not use if bradycardic or heart block.
Requires BP and ECG monitoring.
O 100mg/6–8h is a maintenance dose (check levels).
O Haemofiltration or haemodialysis, if renal failure develops
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Hepatorenal syndrome (HRS)
O Cirrhosis + ascites + renal failure ≈ HRS—if other causes of renal
impairment have been excluded.
O Abnormal haemodynamics causes splanchnic and systemic
vasodilation, but renal vasoconstriction.
O Bacterial translocation, cytokines, and mesenteric angiogenesis
cause splanchnic vasodilation,
O and altered renal autoregulation is involved in the renal
vasoconstriction.
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Hepatorenal syndrome (HRS)
Types of HRS:
HRS 1 is a rapidly progressive deterioration in circulatory and
renal function (median survival <2wks), often triggered by other
deteriorating pathologies.
O Terlipressin resists hypovolaemia.
O Haemodialysis may be needed.
HRS 2 is a more steady deterioration (survival ~6 months).
O Transjugular intrahepatic portosystemic stent shunting may be
required (TIPS).
O Other factors in cirrhosis may contribute to poor renal function.
O Dehydration, covert alcohol use, infection (eg spontaneous
peritonitis), occult GI bleed
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Hepatorenal syndrome (HRS)
O Transplants: Liver transplant may be required.
O After >8–12wks of pre-transplant dialysis, some may be
considered for combined liver–kidney transplantation.
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Management: ALF
O Try to avoid sedatives and other drugs with hepatic
metabolism
O Consider PPI as prophylaxis against stress ulceration, eg
omeprazole 40mg/d IV/PO.
O Liaise early with nearest transplant centre regarding
appropriateness.
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Management: ALF
Treat complications
O Cerebral oedema: On ITU: 20% mannitol IV; hyperventilate.
O Ascites: Restrict fluid (<1.5L/D), low-salt diet(40-100mmol/D),
weigh daily (weight loss of ≤1/2kg/d).
O diuretics (spironolactone 100mg/24h PO; ↑dose as tolerated
(max 400mg/24h)).
O If response is poor, add furosemide ≤120mg/24h PO;
O Do U&E (watch Na+) often.
O Therapeutic paracentesis with concomitant albumin infusion (6–
8g/L fluid removed) may be required.
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Treat complications: ALF
O Bleeding: Vitamin K 10mg/d IV for 3d, platelets, FFP +
blood as needed ± endoscopy.
O Blind Rx of infection: Ceftriaxone 1–2g/24h IV, not
gentamicin (↑risk of renal failure).
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Treat complications:ALF
O ↓Blood glucose: If ≤2mmol/L or symptomatic, Rx 50mL of 50%
glucose IV; check often.
O Encephalopathy: Avoid sedatives; 20° head-up tilt in ITU;
correct electrolytes;
O lactulose 30–50mL/8h (aim for 2–4 soft stools/d) is catabolized
by bacterial flora to short-chain fatty acids which ↓colonic pH
and trap NH3 in the colon as NH4+ ;
O Rifaximin 550mg/12h is a non-absorbable oral antibiotic that ↓
numbers of nitrogen forming gut bacteria.
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Acute Liver Failure
Worse prognosis
O if Grade III–IV encephalopathy,
O age >40yrs,
O albumin <30g/L, ↑INR,
O drug-induced liver failure,
O late-onset hepatic failure worse than fulminant failure.
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Paracetamol poisoning
O 12g (=24 tablets) or 150mg/kg in adults may be fatal.
O If the patient weighs >110kg, calculate ingested dose
using a body weight of 110kg to avoid underestimating
toxicity.
O If the patient is malnourished then 75mg/kg can kill.
Signs and symptoms
O None initially, or vomiting ± RUQ pain.
O Later: jaundice and encephalopathy from liver damage
(the main danger) ± acute kidney injury (AKI).
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Paracetamol poisoning
Management
O General measures:
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Paracetamol poisoning
O GI decontamination is recommended in those presenting <4h
after overdose: give activated charcoal 1g/kg (max 50g).
O Glucose, U&E, LFT, INR, ABG, FBC, HCO3-; blood paracetamol
level at 4h post-ingestion.
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Paracetamol poisoning
O If <10–12h since overdose, not vomiting, and plasma paracetamol
is above the line on the graph, start acetylcysteine.
O If >8–24h and suspicion of large overdose (>7.5g) err on the side of
caution and start acetylcysteine, stopping it if level below
treatment line and INR/ALT normal.
O If ingestion time is unknown, or it is staggered, or presentation is
>15h from ingestion, treatment may still help. Get advice.
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Paracetamol poisoning
O Acetylcysteine is given by IVI:
O 150mg/kg in 5% glucose over 15–60min;
O then 50mg/kg in 500mL of 5% glucose over 4h;
O then 100mg/kg/16h in 1L of 5% glucose.
O Rash is a common SE: treat with chlorphenamine + observe;
O do not stop unless anaphylatoid reaction with shock, vomiting,
and wheeze (occur <10%).
O An alternative (if acetylcysteine unavailable) is methionine
2.5g/4h PO for 16h (total: 10g), but absorption is unreliable if
vomiting
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Paracetamol poisoning
O Ongoing management
• Next day do INR, U&E, LFT. If INR rising, continue acetylcysteine
until <1.4.
• If continued deterioration, discuss with the liver team. Don’t
hesitate to get help.
• Consider referral to specialist liver unit guided by eg King’s College
criteria
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Hepatitis A
O RNA virus.
O Spread: Faecal–oral or shellfish.
O Endemic in Africa and S America, so a problem for travellers.
O Most infections are in childhood.
O Incubation: 2–6wks.
O Symptoms: Fever, malaise, anorexia, nausea, arthralgia—then:
jaundice (rare in children),
O hepatosplenomegaly, and adenopathy.
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Hepatitis A
O Tests: AST and ALT rise 22–40d after exposure (ALT may be
>1000IU/L), returning to normal over 5–20wks.
O IgM rises from day 25 and means recent infection.
O IgG is detectable for life.
O Rx: Supportive. Avoid alcohol. Rarely, interferon alfa for
fulminant hepatitis.
O Active immunization: With inactivated viral protein. 1 IM dose
gives immunity for 1yr (20yrs if further booster is given at 6–12
months).
O Prognosis: Usually self-limiting. Fulminant hepatitis is rare.
Chronicity doesn’t occur.
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Hepatitis E virus (HEV)
O RNA virus. Similar to HAV; common in Indochina (commoner in
older men and also commoner than hepatitis A in UK);
O mortality is high in pregnancy.
O It is associated with pigs.
O Epidemics occur (eg Africa).
O Vaccine is available in China (not Europe).
O Inv: Serology.
O Rx: Nil specific.
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Hepatitis B Virus, HBV
O DNA virus.
O Spread: Blood products, IV drug abusers (IVDU), sexual, direct
contact.
Risk groups:
O IV drug users and their sexual partners/ carers;
O health workers; staff or residents of institutions/prisons;
O haemophiliacs; haemodialysis (and chronic renal failure);
O men who have sex with men; sexually promiscuous;
O foster carers; close family members of a carrier or case;
O babies of HBSAg +ve mothers; adopted child from endemic area.
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Hepatitis B Virus, HBV
O Endemic in: Far East, Africa, Mediterranean.
O Incubation: 1–6 months.
O Signs: Resemble hepatitis A but arthralgia and urticaria are
commoner.
O Tests: HBSAg is present 1–6 months after exposure.
O HBeAg is present for 1½–3 months after acute illness and implies
high infectivity.
O HBSAg persisting for >6 months defines carrier status and occurs
in 5–10% of infections;
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Hepatitis B Virus, HBV
O biopsy may be indicated unless ALT↔ and HBV DNA
<2000iu/mL.
O Antibodies to HBCAg (anti-HBc) imply past infection;
O antibodies to HBSAg (anti-HBs) alone imply vaccination.
O HBV PCR allows monitoring of response to therapy
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Hepatitis B Virus, HBV
O Complications: Fulminant hepatic failure, cirrhosis, HCC,
cholangiocarcinoma, cryoglobulinaemia, membranous
nephropathy, polyarteritis nodosa.
O Rx: Avoid alcohol. Immunize sexual contacts.
O Refer all with chronic liver inflammation (eg ALT ≥30IU/L),
cirrhosis, or HBV DNA >2000IU/mL for antivirals (eg tenofovir,
entecavir).
O Aim - to clear HBSAg and prevent cirrhosis and HCC (risk is ↑↑
if HBSAg and HBeAg +ve).
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Leptospirosis (Weil’s disease)
O spirochaetes belonging to the subgroup Leptospira interrogans.
O Chronic renal infection of carrier animals: rodent, cattle, pigs.
O Spread by water/soil/food contaminated by infected animal
urine.
O Presentation:
O Incubation ~7d (2–30d).
O 1st (acute/septicaemic) phase: fever, non-specific flu-like
symptoms. Mild/subclinical in ~90%.
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Leptospirosis (Weil’s disease)
O Followed by recovery or 2nd (immune/ leptospiruric) phase:
conjunctival suffusion, myalgia (↑CK), jaundice, meningitis, uveitis,
AKI, pulmonary haemorrhage, ARDS, myo/pericarditis.
O (Weil’s disease described in 1886: fever, jaundice splenomegaly,
renal failure, CNS symptoms. Term now applied to all severe
disease.)
O Diagnosis:
O Culture (blood/CSF) +ve during 1st phase.
O Serology. PCR.
O Treatment: Doxycycline, penicillin.
O Conflicting evidence of benefit for steroids in severe disease.
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Alcoholism
O Fatty liver: Acute/reversible, but may progress to cirrhosis if
drinking continues (also seen in obesity, DM, and with
amiodarone).
O Alcoholic hepatitis: 80% progress to cirrhosis (hepatic failure in
10%).
O Cirrhosis: 5yr survival is 48% if drinking continues (if not, 77%).
Biopsy: Mallory bodies ± neutrophil infiltrate
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Managing alcoholic hepatitis
O The patient: Malaise; ↑TPR; anorexia; D&V; tender
hepatomegaly ± jaundice; bleeding; ascites.
O Blood: ↑WCC; ↓platelets (toxic effect or hypersplenism);
↑INR; ↑AST; ↑MCV; ↑urea.
O Jaundice, encephalopathy or coagulopathy ≈ severe hepatitis.
O Most need hospitalizing; urinary catheter and CVP monitoring
may be needed.
O Screen for infections ± ascitic fluid tap and treat for SBP
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Managing alcoholic hepatitis
O Stop alcohol consumption: for withdrawal symptoms, if
chlordiazepoxide by the oral route is impossible, try lorazepam IM.
O Vitamins: vit K: 10mg/d IV for 3d.
O Thiamine 100mg/d PO (high-dose B vitamins can also be given IV
as Pabrinex®—1 pair of ampoules in 50mL 0.9% saline IVI over ½h).
O Optimize nutrition (35–40kcal/kg/d non-protein energy). Use ideal
body weight for calculations, eg if malnourished.
O Don’t use low-protein diets even if severe encephalopathy is
present. Give >1.2g/ kg/d of protein; this prevents
encephalopathy, sepsis, and some deaths.
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Managing alcoholic hepatitis
O Daily weight; LFT; U&E; INR. If creatinine ↑, get help with HRS
O ↓Na+ is common, but water restriction may make matters worse.
O Steroids may confer benefit in those with severe disease.
O The Maddrey Discriminant Factor (DF) = (4.6 ˣ patient’s
prothrombin time in sec – control time) + bilirubin (μmol/L)
roughly reflects mortality.
O If Maddrey score >31 and encephalopathy then consider
prednisolone 40mg/d for 5d tapered over 3wks.
O CI: sepsis; variceal bleeding.
O The largest study to date (STOPAH) showed only a non-significant
trend towards benefit with this regimen.
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Managing alcoholic hepatitis
O Prognosis: Mild episodes hardly affect mortality;
O if severe, mortality ≈ 50% at 30d.
O 1yr after admission for alcoholic hepatitis, 40% are dead...a
sobering thought.
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Autoimmune hepatitis (AIH)
Tests
O Serum bilirubin, AST, ALT, and ALP all usually ↑,
O hypergammaglobulinaemia (esp. IgG),
O +ve autoantibodies (see table 6.12).
O Anaemia, ↓WCC, and ↓platelets indicate hypersplenism.
O Liver biopsy: Mononuclear infiltrate of portal and periportal areas
and piecemeal necrosis ± fibrosis; cirrhosis ≈ worse prognosis.
O MRCP: Helps exclude PSC if ALP ↑ disproportionately.
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Autoimmune hepatitis (AIH)
O Diagnosis
O Depends on excluding other diseases (no lab test is
pathognomonic).
O Diagnostic criteria based on IgG levels, autoantibodies, and
histology in the absence of viral disease are helpful.
O Sometimes diagnosis is a challenge—there is overlap with other
chronic liver disease: eg PBC, PSC and chronic viral hepatitis.
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Autoimmune hepatitis (AIH)
O Management
O Immunosuppressant therapy: Prednisolone
O Liver transplantation
O Prognosis
O 10yr survival ~80%
O The presence of cirrhosis at presentation reduces 10yr survival
from 94% to 62%.
O Overlap syndromes: AIH-PBC (primary biliary cholangitis)
overlap is worse than AIH-AIC (autoimmune cholangitis).
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Wilson’s disease/
hepatolenticular degeneration
O Rare (3/100 000) inherited disorder of copper excretion
with excess deposition in liver and CNS (eg basal ganglia).
O It is treatable, so screen all with cirrhosis.
O Genetics An autosomal recessive disorder of a copper
transporting ATPase, ATP7B.
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Wilson’s disease
O Physiology Total body copper content is ~125mg.
O Intake ≈ 3mg/day (absorbed in proximal small intestine).
O In the liver, copper is incorporated into caeruloplasmin.
O In Wilson’s disease, copper incorporation into caeruloplasmin
in hepatocytes and excretion into bile are impaired.
O Copper accumulates in liver, and later in other organs.
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Wilson’s disease
O Signs
O Children present with liver disease(hepatitis, cirrhosis, fulminant liver
failure);
O Young adults often start with CNS signs: tremor; dysarthria,
dysphagia; dyskinesias; dystonias; dementia; Parkinsonism; ataxia/
clumsiness.
O Mood: Depression/mania; labile emotions; ↕libido; personality
change.
O Cognition: ↓Memory; slow to solve problems; ↓IQ; delusions;
mutism.
O Kayser–Fleischer (KF) rings: Copper in iris (see 6 in following list);
they are not invariable.
O Also: Haemolysis; blue lunulae (nails); arthritis; hypermobile joints;
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grey skin.
Kayser–Fleischer ring
O caused by copper deposition in Descemet's membrane in the
cornea.
O It appears as a greenish-brown pigment at the corneoscleral
junction and frequently requires slit-lamp examination for
identification.
O It may be absent in young children.
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Wilson’s disease
Tests
O Equivocal copper studies need expert interpretation.
O 1. Urine: 24h copper excretion is high, eg >100mcg/24h
(normal <40mcg).
O 2. ↑LFT: non-specific (but ALT >1500 is not part of the picture).
O 3. Serum copper: typically <11μmol/L.
O 4. ↓Serum caeruloplasmin: <200mg/L (<140mg/L is
pathognomonic)—beware incidental low values in protein-
deficiency states (eg nephrotic syndrome, malabsorption).
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Wilson’s disease
O 5. Molecular genetic testing can confirm the diagnosis.
O 6. Slit lamp exam: KF rings: in iris/Descemet’s membrane
O 7. Liver biopsy: ↑Hepatic copper (copper >250mcg/g dry
weight); hepatitis; cirrhosis.
O 8. MRI: degeneration in basal ganglia, fronto-temporal,
cerebellar, and brainstem.
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Wilson’s disease
Management
O Diet: Avoid foods with high copper content (eg liver, chocolate,
nuts, mushrooms, legumes, and shellfish).
O Check water sources (eg wells, pipes) for copper.
O Drugs: Lifelong penicillamine (500mg/6–8h PO for 1yr,
maintenance 0.75–1g/d).
O SES: nausea, rash, ↓WCC, ↓Hb, ↓platelets, haematuria,
nephrosis, lupus.
O Monitor FBC and urinary copper and protein excretion.
O Liver transplantation: If severe liver disease.
O Screen siblings: Asymptomatic homozygotes need treating.
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Wilson’s disease
O Prognosis
O Pre-cirrhotic liver disease is reversible;
O CNS damage less so.
O There are no clear clinical prognostic indicators.
O Fatal events: liver failure, bleeding, infection.
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Thank You
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