Acute Liver Disease & Acute Liver Failure ✅

⚠️ Acute liver disease is not the same as acute liver failure.
Acute liver disease may range from mild hepatocellular injury to life-threatening acute liver failure (ALF). ALF is defined by acute liver injury with impaired synthetic function, usually INR ≥1.5, plus hepatic encephalopathy, in a patient without known pre-existing cirrhosis.

🩺 Acute Liver Disease & Acute Liver Failure

• Acute liver injury: sudden hepatocellular injury with raised ALT/AST, but without encephalopathy.
• Acute severe hepatitis: severe liver injury with jaundice and coagulopathy, but no encephalopathy yet.
• Acute liver failure: acute liver injury with coagulopathy and hepatic encephalopathy.
• Acute-on-chronic liver failure: acute deterioration in a patient with known or previously unrecognised chronic liver disease.
• 🚨 ALF is a medical emergency because deterioration can be rapid, with cerebral oedema, hypoglycaemia, sepsis, renal failure and multiorgan failure.

📊 Classification of Acute Liver Failure

🧠 Causes of Acute Liver Disease & ALF

• 💊 Paracetamol toxicity: most important treatable cause in the UK; risk increased by delayed presentation, staggered overdose, alcohol misuse or malnutrition.
• 💊 Other drugs/toxins: antibiotics, antiepileptics, NSAIDs, statins, antituberculous therapy, herbal remedies, recreational drugs, Amanita phalloides mushrooms.
• 🦠 Viral hepatitis: HAV, HBV, HEV; also HSV, VZV, EBV, CMV and adenovirus, especially in pregnancy or immunosuppression.
• 🛡 Autoimmune hepatitis: may present acutely or as ALF.
• 🧬 Metabolic: Wilson disease, acute fatty liver of pregnancy, Reye syndrome.
• 🤰 Pregnancy-related: HELLP syndrome, acute fatty liver of pregnancy, severe pre-eclampsia.
• 🩸 Vascular/ischaemic: shock liver, Budd–Chiari syndrome, heatstroke, severe cardiac failure.
• 🍷 Alcoholic hepatitis: causes acute severe liver disease but often occurs on a background of chronic liver injury, so distinguish from true ALF.
• ❓ Indeterminate: no cause found despite investigation.

🩺 Clinical Features

• 🤢 Nausea, vomiting, anorexia, malaise and abdominal pain.
• 🟡 Jaundice, dark urine, pale stools and pruritus.
• 🧠 Encephalopathy: sleep disturbance, confusion, agitation, asterixis, reduced consciousness or coma.
• 🩸 Bleeding or bruising from coagulopathy.
• 🍬 Hypoglycaemia, especially in severe hepatocellular failure.
• 🫀 Right upper quadrant pain or tender hepatomegaly may occur.
• 🚫 Stigmata of chronic liver disease are usually absent in true ALF.

🧠 Hepatic Encephalopathy Grades

🩺 Acute Liver Failure vs Chronic Liver Disease

💡 Clinical tip: AST/ALT tell you about hepatocyte injury; INR, glucose, lactate, bilirubin trend and encephalopathy tell you about liver failure. A patient can have ALT >1000 without liver failure, but confusion plus INR elevation is an emergency.

🔎 Initial Investigations

🚑 Immediate Management

• 🚨 Escalate early: involve senior medical, ICU, hepatology and a liver transplant centre if ALF is suspected.
• 🔄 ABCDE assessment: protect airway, give oxygen if needed, support circulation and monitor mental state.
• 🛌 Admit to HDU/ICU if encephalopathy, rising INR, hypoglycaemia, acidosis, renal failure, severe vomiting, sepsis or rapid deterioration.
• 🍬 Prevent hypoglycaemia: frequent glucose checks and IV dextrose if needed.
• 💧 Fluids and electrolytes: correct hypovolaemia, sodium, potassium, phosphate and magnesium carefully.
• 🦠 Infection: culture and treat suspected sepsis promptly; avoid unnecessary delays.
• 🧠 Encephalopathy: avoid sedatives where possible; manage airway risk; treat cerebral oedema urgently if suspected.
• 🩸 Coagulopathy: do not correct INR routinely with FFP unless bleeding or before invasive procedures, because INR is a key prognostic marker.
• 🧪 Serial monitoring: INR, LFTs, glucose, lactate, pH, renal function, phosphate and conscious level.
• 🚫 Avoid hepatotoxins: alcohol, unnecessary paracetamol, NSAIDs and sedatives.

💊 Cause-Specific Treatment

• 💊 Paracetamol toxicity: give IV N-acetylcysteine immediately if indicated; do not wait if high suspicion or delayed presentation.
• 💊 Non-paracetamol ALF: N-acetylcysteine may still be considered early under specialist guidance.
• 🦠 HSV/VZV hepatitis: IV aciclovir if suspected, especially in pregnancy or immunosuppression.
• 🦠 Severe acute HBV: discuss nucleos(t)ide analogue therapy such as tenofovir or entecavir with hepatology.
• 🛡 Autoimmune hepatitis: corticosteroids may be considered by specialists after infection and sepsis are assessed.
• 🍄 Amanita mushroom poisoning: urgent toxicology/hepatology input; consider silibinin where available and transplant assessment.
• 🤰 Pregnancy-related disease: urgent obstetric, anaesthetic and hepatology input; delivery is definitive treatment for HELLP/acute fatty liver of pregnancy.
• 🧬 Wilson disease ALF: urgent transplant-centre discussion; prognosis without transplant is poor.
• 🩸 Budd–Chiari syndrome: anticoagulation and specialist consideration of thrombolysis, TIPS or transplant.
• 🫀 Ischaemic hepatitis: treat shock, hypoxia or cardiac failure.

👑 King’s College Criteria - Transplant Assessment

🚑 King’s College criteria help identify patients who may need urgent liver transplantation. They do not replace clinical judgement: discuss early with a liver transplant centre if ALF is suspected, especially with encephalopathy, rising INR, acidosis, renal failure or lactate elevation.

🧠 Cerebral Oedema & Raised ICP

• More common in hyperacute ALF and grade 3–4 encephalopathy.
• Warning signs: falling GCS, agitation, pupillary changes, hypertension/bradycardia, seizures or abnormal posturing.
• Manage in ICU with head-up positioning, avoidance of hypoxia/hypotension, controlled ventilation if intubated, and specialist osmotherapy such as hypertonic saline or mannitol.
• Avoid hyponatraemia and fever; maintain adequate cerebral perfusion.

⚠️ Complications

• 🍬 Hypoglycaemia.
• 🩸 Coagulopathy and bleeding.
• 🧠 Cerebral oedema and raised intracranial pressure.
• 🦠 Infection and sepsis.
• 🫘 Acute kidney injury and hepatorenal physiology.
• 🫁 Respiratory failure or aspiration.
• 🧪 Metabolic acidosis, lactate elevation and electrolyte abnormalities.
• 🫀 Multiorgan failure.

📝 Exam Pearls

• ⚠️ Acute liver injury becomes acute liver failure when there is coagulopathy plus encephalopathy.
• 🧪 ALT >1000 suggests paracetamol toxicity, viral hepatitis or ischaemic hepatitis.
• 🩸 INR is more important than ALT for assessing liver failure severity.
• 🍬 Always check glucose: hypoglycaemia can be life-threatening.
• 💊 Check a paracetamol level even if overdose is not disclosed.
• 🚑 Early transplant-centre discussion saves lives; do not wait until the patient is moribund.
• 🧠 Lactulose is standard for chronic hepatic encephalopathy, but in ALF the priority is ICU-level cerebral oedema and airway management.

🧠 Teaching Note

Acute liver failure is dangerous because the liver suddenly loses its ability to perform synthetic, metabolic and detoxifying functions. INR rises because clotting factors have short half-lives, glucose falls because hepatic glycogen and gluconeogenesis fail, and encephalopathy develops as toxins and inflammatory mediators affect the brain. Marked ALT/AST means hepatocytes are injured, but it does not by itself prove liver failure. The key bedside question is: is the patient coagulopathic, hypoglycaemic, acidotic or encephalopathic?

📚 References & UK Resources

• EASL Clinical Practice Guidelines – Acute Liver Failure
• RCEM Learning – Acute Liver Failure
• BNF/NICE – Poisoning, emergency treatment
• TOXBASE – UK poisons information
• NHS Blood and Transplant – Liver transplantation