Definition and Causes
the development of hepatic encephalopathy in a patient without pre-existing liver disease. The liver must fail rapidly (typically within 26 weeks of the onset of jaundice), and the encephalopathy must develop within this time frame. This distinguishes ALF from acute-on-chronic liver failure (ACLF), where there is underlying cirrhosis.
In the UK, the most common causes of ALF are paracetamol overdose (accounting for over 50% of cases), idiosyncratic drug reactions (antibiotics, anticonvulsants, herbal remedies), acute viral hepatitis (hepatitis A, B, E — hepatitis C rarely causes ALF), autoimmune hepatitis, Wilson’s disease (in young patients presenting with haemolytic anaemia and liver failure), Budd-Chiari syndrome, and pregnancy-related liver disease (acute fatty liver of pregnancy, HELLP syndrome).
| Cause | Typical Presentation | Key Investigation |
| Paracetamol overdose | History of overdose; often 48–72h post-ingestion | Serum paracetamol level; paracetamol-protein adducts |
| Drug-induced (non-paracetamol) | Recent new medication; exclude other causes | Drug history; liver biopsy if diagnosis unclear |
| Hepatitis A | Travel history; shellfish exposure; contact with jaundiced person | HAV IgM |
| Hepatitis B | IV drug use, sexual exposure, vertical transmission | HBsAg, HBcAb IgM; HBV DNA |
| Autoimmune hepatitis | Young woman; other autoimmune disease; high IgG | ANA, ASMA, LKM antibody; high IgG; biopsy |
| Wilson’s disease | Young patient; haemolytic anaemia; Kayser-Fleischer rings; low ALP | Serum caeruloplasmin; 24h urine copper; slit-lamp examination |
| Budd-Chiari syndrome | Hepatomegaly; ascites; hypercoagulable state | Doppler USS liver; CT hepatic veins |