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The second of this four-part review encompasses the inpatient management of hepatic encephalopathy (HE) in patients with decompensated cirrhosis, acute-on-chronic liver failure (ACLF) and acute liver failure (ALF). The management of overt HE in cirrhosis consists of excluding alternative causes of altered mental state, identifying and correcting precipitants, instigating nutritional support and initiating pharmacological therapy. The presence of HE in combination with other organ failures defines ACLF, and these patients are frequently managed in the intensive care setting. Aside from the treatment of precipitants and organ support in ACLF, there is an emerging role for emergency liver transplantation in highly selected patients. ALF is characterised by the development of severe hepatocellular injury accompanied by coagulopathy and HE, in patients usually without pre-existing chronic liver disease. The often rapid development of hyperammonaemia in ALF may culminate in cerebral oedema and intracranial hypertension, which is specific to this syndrome and, as such, management of HE in ALF differs from that in cirrhosis. A package of neuroprotective care is delivered, including specific monitoring for cerebral oedema, and osmotic therapy is employed for surges in intracranial pressure. Specific ammonia-lowering therapies recommended include continuous renal replacement therapy and therapeutic plasma exchange, with emergency liver transplantation the definitive treatment in the absence of liver regeneration and spontaneous recovery. Independent of underlying aetiology, patients with grade 3–4 HE should be managed in the intensive care unit due to risk of airway compromise and aspiration.