Write a short note on acute liver failure.

Definition

Acute liver failure (ALF, fulminant hepatic failure) is the development of severe acute liver injury with coagulopathy (INR ≥ 1.5) and hepatic encephalopathy in a patient without pre-existing liver disease, evolving within 26 weeks of the onset of illness.

Subclassification by the interval between jaundice and encephalopathy carries prognostic weight:

• Hyperacute (< 7 days) — typically paracetamol and viral hepatitis; highest rate of cerebral oedema but the BEST spontaneous survival
• Acute (8–28 days)
• Subacute (29 days–12 weeks) — less cerebral oedema but worst prognosis, often from drug injury and seronegative hepatitis

Aetiology

Clinical Features

• Jaundice, often deepening rapidly.
• HEPATIC ENCEPHALOPATHY — the defining feature, graded I to IV, with asterixis in early grades and coma in grade IV.
• Coagulopathy with bleeding — the INR is the key marker and must not be corrected prophylactically, as it is the main index of progression.
• CEREBRAL OEDEMA AND RAISED INTRACRANIAL PRESSURE — the leading cause of death in hyperacute failure: hypertension with bradycardia, abnormal pupillary responses, decerebrate posturing, and papilloedema (late).
• Hypoglycaemia — from failure of gluconeogenesis and glycogen depletion; profound and recurrent, and a frequent avoidable cause of death.
• Metabolic acidosis with hyperlactataemia; hyponatraemia, hypokalaemia, hypophosphataemia.
• Circulatory failure — vasodilated, hyperdynamic circulation resembling sepsis.
• Acute kidney injury — hepatorenal, acute tubular necrosis, or direct paracetamol nephrotoxicity.
• Sepsis — bacterial and fungal infection is very common, and fever and leucocytosis are often absent.
• Respiratory failure and ARDS; pancreatitis; adrenal insufficiency.

Investigations

• INR/prothrombin time and sensorium — the two measurements that must be repeated frequently; both determine prognosis and transplant listing.
• Liver function tests, glucose (hourly initially), arterial blood gas with lactate, ammonia, electrolytes, renal function, phosphate.
• Aetiological workup: paracetamol level, viral serology (anti-HAV IgM, HBsAg with anti-HBc IgM, anti-HEV IgM), autoantibodies and immunoglobulins, caeruloplasmin, serum and urinary copper, pregnancy test, toxicology, and Doppler ultrasound of hepatic veins for Budd–Chiari.
• CT head to exclude other causes of encephalopathy and assess cerebral oedema.
• Blood, urine and sputum cultures — surveillance cultures, given the frequency of occult sepsis.

Management

Acute liver failure is managed in an intensive care unit, ideally in a transplant centre — early transfer is essential and often left too late.

1. Specific therapy where available

• N-acetylcysteine — for paracetamol poisoning, and it also improves outcome in NON-paracetamol acute liver failure; give it early in all cases.
• Antivirals for hepatitis B; aciclovir for herpes; penicillin and silibinin for *Amanita*; chelation and consideration of transplant in Wilson's disease; urgent delivery in acute fatty liver of pregnancy and HELLP.
• Withdraw all hepatotoxic drugs.

2. Supportive care — the substance of management

• Neurological: nurse head-up at 30°, avoid stimulation, maintain normocapnia and normothermia (or mild hypothermia), hypertonic saline or mannitol for raised intracranial pressure; lactulose has limited evidence in ALF; sedation for grade III–IV; intubate and ventilate for grade III–IV encephalopathy.
• Metabolic: infuse dextrose continuously and check glucose hourly — hypoglycaemia is easily missed in a sedated patient; correct electrolytes and phosphate.
• Coagulopathy: do NOT correct the INR prophylactically — it is the principal prognostic marker and correcting it blinds you to the trend. Give vitamin K, and use plasma or factor concentrates only for active bleeding or before an invasive procedure.
• Infection: low threshold for empirical broad-spectrum antibiotics and antifungals, since sepsis precipitates deterioration and can preclude transplantation; surveillance cultures.
• Renal: avoid nephrotoxins; continuous renal replacement therapy (preferred over intermittent, for haemodynamic and intracranial stability).
• Circulatory: fluids and vasopressors; hydrocortisone for vasopressor-resistant hypotension.
• Nutrition: early enteral feeding with adequate protein — protein restriction is not indicated.
• Stress ulcer prophylaxis.

3. Liver transplantation — the definitive treatment

Refer EARLY to a transplant centre — before the patient becomes too unstable to transfer. Listing is guided by the King's College Criteria:

• Paracetamol-induced: arterial pH < 7.3 after resuscitation, OR the triad of INR > 6.5, creatinine > 3.4 mg/dL and grade III–IV encephalopathy; a raised arterial lactate is an additional early indicator.
• Non-paracetamol: INR > 6.5 alone, OR any three of: age < 10 or > 40 years, unfavourable aetiology (drug reaction, seronegative hepatitis), jaundice-to-encephalopathy interval > 7 days, INR > 3.5, bilirubin > 17.5 mg/dL.