About This Page
This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Acute liver failure (ALF): severe hepatic dysfunction + coagulopathy (INR >1.5) + encephalopathy in a patient WITHOUT pre-existing liver disease
- Commonest cause of ALF in the UK: paracetamol overdose. Other causes: viral hepatitis, drug reactions, autoimmune, Wilson disease, Budd-Chiari
- King's College criteria guide decision for emergency liver transplant listing (different criteria for paracetamol vs non-paracetamol)
- Hepatic encephalopathy: confusion → coma from ammonia accumulation. Treat precipitants + lactulose + rifaximin
- Contact regional liver transplant centre EARLY for any patient with acute liver failure — do not delay
Overview
Liver failure occurs when the liver loses its ability to perform essential synthetic, metabolic, and detoxification functions. Acute liver failure (ALF) is defined as the development of coagulopathy (INR >1.5) and hepatic encephalopathy in a patient without pre-existing chronic liver disease, within 26 weeks of symptom onset. It is further classified by onset: hyperacute (<7 days, e.g. paracetamol), acute (7–21 days), and subacute (21 days–26 weeks). Hepatic encephalopathy (HE) refers to a spectrum of neuropsychiatric abnormalities caused by accumulation of neurotoxins (primarily ammonia) due to impaired hepatic clearance and/or portosystemic shunting.
Epidemiology
Acute liver failure is relatively rare, with approximately 400–600 cases per year in the UK. Paracetamol overdose accounts for approximately 50–60% of UK ALF cases, making it the commonest cause. Non-paracetamol ALF has worse prognosis (higher transplant-free mortality). Hepatic encephalopathy occurs in up to 50% of patients with cirrhosis and is the defining feature of decompensation that most impacts quality of life. Overall, ALF has approximately 50% transplant-free survival.
Clinical Features
Symptoms
Jaundice (rapidly progressive in ALF)
Confusion, personality change, disorientation (encephalopathy grade I–II)
Drowsiness progressing to coma (encephalopathy grade III–IV)
Nausea, vomiting, anorexia
RUQ pain (hepatic capsule stretch)
Easy bruising or bleeding (coagulopathy)
Signs
Asterixis (flapping tremor) — grade II encephalopathy
Fetor hepaticus (sweet musty breath — from dimethyl sulphide)
Hyperreflexia progressing to hyporeflexia (deteriorating encephalopathy)
Jaundice (deep in ALF)
Tender hepatomegaly initially, then shrinking liver (massive necrosis)
Signs of cerebral oedema in ALF: papilloedema, hypertension, bradycardia (Cushing reflex)
Hypotension (multiorgan failure in severe ALF)
Investigations
First-line
LFTsMarkedly raised transaminases (often >1000 IU/L in ALF — especially paracetamol). Rising bilirubin. Falling albumin
Coagulation (INR/PT)INR >1.5 = defines liver failure. Do NOT correct with FFP unless actively bleeding (INR trend is a critical prognostic marker)
U&Es, glucose, lactate, ABGRenal impairment (hepatorenal), hypoglycaemia (impaired gluconeogenesis), metabolic acidosis (lactic acidosis in paracetamol OD — poor prognosis)
Paracetamol levelIn all cases of unexplained ALF (staggered overdose may be occult)
Ammonia levelArterial ammonia — correlates with encephalopathy severity. >150 µmol/L in ALF = high risk of cerebral oedema
Second-line
Liver screenHepatitis A/B/C/E serology, autoantibodies (ANA, SMA, IgG), caeruloplasmin and urinary copper (Wilson disease — especially if age <40 with haemolytic anaemia), ferritin
Abdominal USS with DopplerAssess liver size, hepatic vein patency (Budd-Chiari), portal vein thrombosis
King's College criteriaPredict need for transplant. Paracetamol: arterial pH <7.3 after resuscitation, OR (INR >6.5 + creatinine >300 + grade III–IV HE). Non-paracetamol: INR >6.5, OR ≥3 of: age <10 or >40, non-A/non-B hepatitis, jaundice >7 days before HE, bilirubin >300, INR >3.5
Specialist
CT headIf sudden neurological deterioration — assess for cerebral oedema (a major cause of death in ALF)
Liver biopsy (transjugular)If aetiology unclear — may show massive hepatic necrosis, autoimmune features, or Wilson disease
1
Acute liver failure — immediate
- Transfer/contact regional liver transplant centre EARLY — do not wait for King's criteria to be met
- HDU/ICU admission with continuous monitoring
- N-acetylcysteine (NAC): give for paracetamol OD (per Prescott protocol). Also beneficial in non-paracetamol ALF
- Correct hypoglycaemia: IV dextrose infusion (10–20% dextrose)
- Do NOT correct coagulopathy with FFP unless actively bleeding — INR trend is a vital prognostic marker
2
Hepatic encephalopathy
- Identify and treat precipitants: infection/SBP, GI bleeding, constipation, dehydration, electrolyte disturbance, sedative/opioid use, high-protein diet is NOT a cause
- Lactulose: oral or NG, titrate to 2–3 soft stools/day (reduces colonic ammonia production/absorption)
- Rifaximin 550 mg BD: add for recurrent HE (secondary prophylaxis — reduces readmissions by 50%)
- Avoid sedating medications (benzodiazepines, opioids) — worsen encephalopathy
- Nutrition: adequate protein intake (1.2–1.5 g/kg/day) — protein restriction is NOT recommended
3
Cerebral oedema (ALF)
- Nurse head up 30°
- Avoid stimulation, minimal handling
- IV mannitol 20% (1 g/kg) for clinical signs of raised ICP
- Hypertonic saline to maintain serum sodium 145–150 mmol/L (osmotic therapy)
- Consider intracranial pressure monitoring in grade III–IV HE
4
Liver transplant
- Emergency super-urgent listing if King's College criteria met (or equivalent poor prognostic markers)
- Transplant can be life-saving — 1-year post-transplant survival ~80%
- Contraindicated if: irreversible brain damage, uncontrolled sepsis, active substance misuse, extrahepatic malignancy
Complications
- Cerebral oedema: Major cause of death in ALF — from cytotoxic brain swelling due to astrocyte ammonia metabolism
- Multiorgan failure: Renal (HRS/ATN), cardiovascular (distributive shock), respiratory (ARDS)
- Coagulopathy and bleeding: But paradoxically also at risk of thrombosis (rebalanced haemostasis)
- Sepsis: Immune dysfunction in liver failure — high risk of bacterial and fungal infections
- Hypoglycaemia: From impaired hepatic gluconeogenesis — can be severe and require IV dextrose
UKMLA Exam Tips
- 1ALF = coagulopathy (INR >1.5) + encephalopathy + NO pre-existing liver disease — all three criteria required
- 2Paracetamol is the commonest cause of ALF in the UK. Always check paracetamol level in ANY unexplained ALF
- 3King's College criteria (paracetamol): pH <7.3 post-resuscitation, OR INR >6.5 + Cr >300 + Grade III/IV HE
- 4Do NOT correct INR with FFP unless actively bleeding — you lose your most important prognostic marker
- 5Asterixis (flapping tremor) = grade II hepatic encephalopathy. Ask patient to dorsiflex wrists with arms outstretched
- 6NAC works for paracetamol AND non-paracetamol ALF — give it in all cases
- 7Protein restriction does NOT prevent or treat hepatic encephalopathy — this is an outdated practice
- 8Contact transplant centre EARLY — do not wait for criteria to be fully met
practicetest your knowledge on liver failureApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — gastroenterology and beyond.
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