ALF is not simply a hepatic emergency — it causes a cascade of severe multisystem complications that each require active management. The degree to which these complications occur determines prognosis and the need for emergency transplantation.

Hepatic Encephalopathy

Hepatic encephalopathy (HE) in ALF results from the accumulation of ammonia and other gut-derived neurotoxins in the systemic circulation (due to failure of hepatic detoxification), combined with inflammatory mediators crossing the blood-brain barrier and causing astrocyte swelling and cerebral oedema. It is graded I–IV: Grade I (subtle changes in personality, mild confusion), Grade II (drowsy but rousable, disoriented), Grade III (deeply drowsy, incoherent, aggressive), Grade IV (coma, unresponsive).

Grade III-IV encephalopathy carries a high risk of cerebral oedema and raised ICP. These patients should be intubated for airway protection, nursed with head up at 30°, and monitored for ICP elevation. ICP monitoring should be considered in patients with Grade IV encephalopathy, particularly if transplant is being planned. Management includes lactulose to reduce intestinal ammonia production, rifaximin, protein restriction (mild, not complete), and treatment of precipitating factors.

Coagulopathy

The liver synthesises all coagulation factors except von Willebrand factor. ALF therefore causes profound coagulopathy — the prothrombin time and INR are the most sensitive markers of synthetic function and the key prognostic parameters. A rapidly rising INR is both a diagnostic marker of ALF and an indication for transplant assessment. Paradoxically, ALF also reduces the production of anticoagulant proteins (protein C, protein S, antithrombin), so patients may be in a state of ‘rebalanced’ haemostasis and are not necessarily auto-anticoagulated — VTE prophylaxis should still be considered.

Coagulopathy should not be corrected with fresh frozen plasma (FFP) unless active bleeding is occurring or an invasive procedure is required, because this masks the INR as a prognostic marker and risks volume overload. Vitamin K should be given to all ALF patients in case there is a dietary or absorption component to the coagulopathy.

Renal Failure

Acute kidney injury occurs in 40–50% of patients with ALF, most commonly as hepatorenal syndrome (HRS — functional renal failure from renal vasoconstriction mediated by splanchnic vasodilation) or as direct drug-induced tubular toxicity (particularly in paracetamol poisoning). Management includes ensuring adequate circulating volume, stopping nephrotoxic drugs, and renal replacement therapy if required. Renal failure in the context of ALF is associated with a very poor prognosis without transplantation.

Hypoglycaemia

Profound hypoglycaemia is a distinctive and dangerous feature of ALF, resulting from failure of hepatic glycogenolysis and gluconeogenesis. Blood glucose must be monitored at least hourly in Grade II–IV encephalopathy and 10% or 50% dextrose given promptly to maintain glucose above 4 mmol/L. Hypoglycaemia in ALF can be sudden and severe and must never be allowed to occur.

Infection

Bacterial infection — particularly spontaneous bacterial peritonitis, pneumonia, and line-related bacteraemia — occurs in up to 80% of ALF patients. This is partly due to impaired hepatic immune function (Kupffer cell dysfunction), translocation of gut bacteria, and the multiplicity of invasive devices. Fungal infection is also common. A low threshold for antibiotic treatment is appropriate — fever, rising white cell count, or unexplained deterioration should prompt blood cultures and broad-spectrum antibiotics.