Overview Acute liver failure is a rare but life-threatening critical illness that occurs most often in patients who do not have preexisting liver disease. Acute liver failure is seen most commonly in previously healthy adults in their 30s and presents unique challenges in clinical management. The clinical presentation usually includes hepatic dysfunction, abnormal liver biochemical values, and coagulopathy; encephalopathy may develop, with multiorgan failure and death occurring in up to half the cases

• Travelling overseas - hepatitis
• Age
• Cardiorespiratory failure
• Mental illness

Clinical Presentation of Acute Liver Injury

• Jaundice (defining feature)
• Pruritis
• Symptoms of hepatic encephalopathy (Grading Encephalopathy is Important!)
• Abdominal pain
• Nausea/vomiting
• Malaise

Clinical Examination of Acute Liver Failure

• Signs of hepatic encephalopathy (Grading is important!)
  • Confusion, somnolence, coma
  • Hyperreflexia
  • Nystagmus
  • Asterixis
  • Clonus

• Jaundice
• Vesicular skin lesions - herpes simplex virus
• Kayser-Fleisher rings - Wilson disease
• Fever
• Right upper quadrant tenderness and hepatomegaly
• Ascites
• Signs of intravascular volume depletion, such as orthostatic hypotension
• Features of preeclampsia, such as hypertension (HELLP syndrome)

Acute hepatic failure is defined by a rapid decline in hepatic function characterised by jaundice, coagulopathy (INR >1.5), and hepatic encephalopathy in patients with no evidence of prior liver disease. Therefore:

• First exclude underlying chronic liver disease (ex. cirrhosis). The following signs suggest chronic liver disease or cirrhosis is underlying acute presentation:
  • Splenomegaly
  • Spider angiomata
  • Palmar errythema
  • Ascites

• Severe acute hepatitis
• Cholestasis

Determining the aetiology of acute liver failure requires a combination of history taking, laboratory tests, and imaging studies.

• Paracetamol hepatotoxicity (50% - most common in developed countries)
  • Equally divided between intentional and unintentional cases
• Idiosyncratic drug-induced liver injury (11%)
• Viruses - Common in developing countries
  • Hepatitis A
  • Hepatitis B
  • Hepatitis E
• Autoimmune hepatitis
• Ischaemic hepatitis - patients with underlying cardiac/respiratory failure
• Pregnancy related syndrome
• Budd-Chiari syndrome
• Mushroom ingestion - Amanita phalloides
• Wilson's disease
• Malignancy

Bedside

• ECG
• Blood glucose - may be dangerous low

Serology

• LFT - Often elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)
• Prothrombin time/INR
  • INR >1.5 is a defining feature of ALF
• EUC - renal failure is often a complication
• Serum Ammonia - may be dramatically elevated → risk of intracranial hypertension
• FBC
• Coagulation studies
• ABG
• Amylase/Lipase
• Paracetamol level
• Viral Hepatitis serology (Hep A, B, C, D, E)
• ANA - for autoimmune hepatitis
• Ceruloplasmin - if Wilson disease suspected

Imaging

• Chest X-ray
• CT abdomen- for evidence of Budd Chari syndrome and also in cases of severe encephalopathy
• Liver ultrasound +/- Fibroscan - if chronic liver disease suspected

Initial resuscitation 

• ABCD
• Determination of aetiology
• Assessment of the severity of the disease and the associated prognosis
  • Investigations specified above
• Treatment of specific cause
  • Acute acetaminophen overdose is treated with N-acetylcysteine
  • Hepatitis - oral nucleoside or nucleotide analogue
  • Suspected mushroom (Amanita phalloides) poisoning
    • IV fluids + gastric lavage + activated charcoal
    • benzylpenicillin
    • acetylcysteine
  • Autoimmune hepatitis - glucocorticoids

Supportive Treatment

• Monitoring - Daily laboratory testing
  • LFTs
  • Coagulation profile
  • FBC
  • EUC
  • ABG
  • CMP
  • Glucose
• Prevention or treatment of complications
  • Cardiovascular
    • Hypotension - Vasopressors (noradrenaline)
    • Decrease cardiac output and right ventricular failure - assess with echocardiogram
  • Respiratory - 30% 0f cases
    • Pulmonary oedema
    • Infection
  • Neurological
    • Encephalopathy - sedate and prophylactic osmotherapy → ↓ammonia →↓intracranial hypertension
    • Intracranial hypertension - hyperventilation to induce hypocapnia →↓intracranial hypertension
      • ?Lactulose
    • Seizures → Lamotrogine
  • Metabolic and renal - 50% of cases common in the elderly
    • Hypoglycaemia - dextrose infusion
    • Hyponaturaemia - Hypertonic saline
    • Hypokalaemia - KCl IV
    • Acute renal failure
  • Haematological
    • Coagulopathy - Vitamin K, Fresh frozen plasma
• Liver transplantation when spontaneous survival is considered unlikely
• Possible use of liver support devices

Complications

•  Cardiovascular
  • Hypotension
  • Decrease cardiac output and right ventricular failure
• Respiratory - 30% 0f cases
  • Pulmonary oedema
  • Infection
• Neurological
  • Encephalopathy
  • Intracranial hypertension
• Metabolic and renal - 50% of cases common in the elderly
  • Hypoglycaemia
  • Hyponaturaemia
  • Acute renal failure
• Haematological
  • Coagulopathy

Prognosis Only 40 percent of patients with acute liver failure recover spontaneously, leaving many in need of a liver transplantation, and even those who do eventually recover are often gravely ill

Liver transplantation The decision to proceed with liver transplantation depends upon the probability of spontaneous hepatic recovery. Results in average 1-yr survival rates of about 80%. Transplantation is thus recommended if prognosis without transplantation is worse

UpToDate
NEJM - Acute Liver Failure 2014