Acute Liver Failure

• A rare syndrome defined by a rapid decline in hepatic

junction characterized by jaundice, coagulopathy
(INR>1.5), and hepatic encephalopathy in patients
with no evidence of prior liver disease.

• The interval from onset of jaundice to

encephalopathy = 24 – 26 weeks
 Epidemiology
• A study in 19 US, 1 Canadian and 2 UK centres
– found mean age of onset 38 year (range 17-79)
– More common in female (67%)
– 45% spontaneous recovery
– 25% required transplant
– 30% mortality

Lee WM, Squires RH Jr, Nyberg SL et. al. Acute Liver Failure: Summary of a workshop.
Hepatology. 2008: 47:1401-1415
 Etiology
• According to the same study:
Causes %
Acetaminophen hepatotoxicity 46%

Indeterminate 14%

Idiosyncratic drug-induced liver injury 11%

Acute hepatitis B 8%

Autoimmune hepatitis 6%

Shock liver 4%

Acute hepatitis A 3%

Lee WM, Squires RH Jr, Nyberg SL et. al.

Etiology:
 Pathophysiology
• Massive hepatic fibrosis  Organ failure
• Some cases have no hepatic necrosis eg: Fatty liver of
pregnancy and Reye’s syndrome
• Paracetamol is predominantly metabolized in the
liver through glucuronidation and sulphation, with a
small amount metabolized by the cytochrome P450
system.
• A toxic intermediate N-acetyl-p-benzoquinone imine
(NAPQI), generated vis cytochrome P450 pathway is
subsequently conjugated by glutathione.
• If overdosed, glutathione storage depleted, resulting
in direct hepatic injury by NAPQI.

• Induction of the P450 system through chronic

alcohol use or barbiturates and depletion of
glutathione stores in settings such as nutritional
deficiency may result in a greater propensity to
develop paracetamol hepatotoxicity.
Classification: Jaundice to
encephalopathy
 Classification: from onset of illness to
encephalopathy

• Fulminant if less than 8 weeks

• Late onset if between 8-26 weeks

 Risk factors
• Strong
– Chronic alcohol abuse
– Poor nutritional status
– Female sex
– Age >40 years
– Pregnancy
– Chronic hepatitis B
– Chronic pain and
narcotic use
• Weak
– Paracetamol and
antidepressant therapy
– Chronic hepatitis C
– HIV and hepatitis C co-
infection
 Clinical features
Mainly:
• Presence of risk factors
• Hepatotoxic medication
• Jaundice
• Hepatic encephalopathy
 Other features
• Absence of history of chronic liver disease
• Abdominal pain
• Nausea, vomiting
• Malaise
• Signs of cerebral edema
• Right upper quadrant tenderness
• Hepatomegaly
• Absence of signs of chronic liver disease
• Depression or suicidal ideation
• Exposure to hepatotoxins
• Illicit drug abuse and high-risk behaviors
 Investigations
Test
liver function tests
prothrombin time/INR
basic metabolic panel
FBC
Urinalysis
arterial blood gas
paracetamol (acetaminophen) level
urine toxicology screen
Result
hyperbilirubinaemia, elevated liver enzymes
elevated INR (>1.5)
elevated urea and creatinine, metabolic derangements
leukocytosis, anaemia, thrombocytopenia
urobilinogen positive
metabolic acidosis
may be elevated
may be positive for paracetamol (acetaminophen)
factor V level low (<20% to 30% of normal)

viral hepatitis serologies may be positive

autoimmune hepatitis markers may be positive (ANF, ASMA, LKM)

serum ceruloplasmin low (<50 mg/L [<5 mg/dL]) in Wilson's disease

Serum copper, urinary copper, slit- High copper, Kayser-Fleischer Rings

lamp eye examination

abdominal ultrasound with Doppler hepatic vessel thrombosis, hepatomegaly,

splenomegaly, hepatic surface nodularity

Cholangiography (MRCP or ERCP) Gallstone may be present

 Differential diagnoses
Points for the diagnosis Diagnoses Points against the
diagnosis
- Jaundice, coagulopathy Severe acute hepatitis - No hepatic
encephalopathy

- Jaundice, abdominal Cholestasis - No hepatic

pain, fever in case of encephalopathy
cholangitis - No coagulopathy

- Jaundice, abdominal Hemolysis - No coagulopathy

pain due to sickle cell - No hepatic
hepatopathy in case of encephalopathy
sickle cell anemia
 Treatment
• Early transfer to a specialized transplant unit
• Conservative treatment
– Vital signs monitoring
– Neurological status monitoring (ICP, GCS)
– Monitor fluid, blood glucose, electrolyte and
cultures
– Liver transplantation assessment
• Treat the cause
– Paracetamol overdose – N-acetyl cysteine
– Budd-Chiari syndrome – anticoagulant
– Amanita mushroom poisoning – IV fluid + gastric
lavage + activated charcoal
– Autoimmune hepatitis – methylprednisolone
– Acute hepatitis B – oral nucleoside or nucleotide
analogue
– Acute Wilson’s disease – decrease serum copper
(plasmapheresis)
 References
• Davidson’s Principles and Practice of Medicine 21st
Ed.
• BestPractice BMJ: Acute liver failure