Acute Liver Failure
A life-threatening emergency — rapid recognition, N-acetylcysteine, and transplant assessment
Acute liver failure (ALF) is a rare but life-threatening condition in which rapid deterioration of liver function causes coagulopathy and encephalopathy in a patient without pre-existing liver disease. It is a medical emergency requiring immediate specialist management and early consideration of liver transplantation. Careful evaluation of the cause, severity, and trajectory is essential from the moment of presentation.
What is Acute Liver Failure?
Acute liver failure is defined as the development of coagulopathy (INR ≥1.5) and any degree of hepatic encephalopathy in a patient without pre-existing chronic liver disease, within 26 weeks of the onset of illness. It is classified by the time from jaundice to encephalopathy: hyperacute (0–7 days, e.g. paracetamol overdose), acute (8–28 days), and subacute (4–26 weeks). The distinction matters because hyperacute ALF, despite the most severe encephalopathy, often has the best spontaneous survival. Massive hepatocyte necrosis results in failure of detoxification, protein synthesis, and metabolic function.
Common Causes
The most common cause in the UK is paracetamol overdose (intentional or accidental), accounting for approximately 50% of all cases. Other important causes include viral hepatitis (hepatitis A, B, E — particularly in pregnancy), drug-induced liver injury (DILI) from antibiotics, antituberculosis drugs, or herbal preparations, Wilson's disease presenting acutely, autoimmune hepatitis, Budd-Chiari syndrome, ischaemic hepatitis ('shock liver'), and acute fatty liver of pregnancy. In a significant proportion of cases no cause is identified (seronegative or non-A non-E hepatitis).
Clinical Features and Complications
Jaundice is usually the presenting feature, followed by coagulopathy (prolonged PT/INR) and then encephalopathy as the condition progresses. Complications include cerebral oedema (leading to raised intracranial pressure and brainstem herniation), acute kidney injury (hepatorenal syndrome or direct tubular injury in paracetamol overdose), hypoglycaemia (from failure of hepatic gluconeogenesis), infections (including sepsis and fungal infections), metabolic acidosis, and haemodynamic instability. Hepatic encephalopathy grades from I (mild confusion) to IV (coma). Grade III–IV encephalopathy represents critical illness requiring ICU care.
Management
All patients with ALF should be managed in, or transferred to, a specialist liver unit. N-acetylcysteine (NAC) is given intravenously in all cases of paracetamol-induced ALF — it replenishes glutathione and prevents further hepatocyte injury. It should be given even if presentation is delayed beyond 24 hours. There is also emerging evidence for NAC benefit in non-paracetamol ALF. Specific antidotes or treatments are given for other causes where available: antivirals for hepatitis B, chelation therapy for Wilson's disease, and steroids for autoimmune hepatitis. Supportive care in ICU includes: correction of hypoglycaemia (10% or 50% IV dextrose), fresh frozen plasma (FFP) or vitamin K only if actively bleeding or before procedures, management of cerebral oedema (head elevation, mannitol, hypertonic saline, intracranial pressure monitoring), renal replacement therapy (haemofiltration), prophylactic antibiotics and antifungals, and haemodynamic support with vasopressors if required. This article has been prepared following careful evaluation of NICE, BSG, and King's College Hospital criteria for acute liver failure management.
King's College Criteria and Transplant
Liver transplantation is the only definitive treatment for ALF not responding to medical management. The King's College Criteria (KCC) are used to identify patients unlikely to survive without transplantation. For paracetamol-induced ALF, transplant is considered if: arterial pH <7.3 after resuscitation, or all three of: PT >100 seconds, creatinine >300 µmol/L, and Grade III–IV encephalopathy. For non-paracetamol ALF: INR >6.5, or any three of: age <10 or >40, drug-induced/seronegative aetiology, jaundice-to-encephalopathy interval >7 days, bilirubin >300 µmol/L, INR >3.5. All patients meeting KCC should be urgently listed for a superurgent liver transplant.