Management of hepatic encephalopathy

Definition and classification. Brain dysfunction caused by liver failure and/or portosystemic shunting, ranging from subclinical impairment to coma. Type A — acute liver failure; Type B — portosystemic bypass without intrinsic liver disease; Type C — cirrhosis. Severity is graded by the West Haven criteria I–IV; covert HE comprises minimal HE plus grade I.

Identify and treat precipitants — the mainstay of management. Infection (SBP, urinary and chest), gastrointestinal bleeding, constipation, dehydration and excessive diuresis, hypokalaemia and hyponatraemia, sedatives and opioids, alcohol binge, portal vein thrombosis, TIPS and hepatocellular carcinoma. In an older patient always exclude other causes of delirium, subdural haematoma, hypoglycaemia and drug toxicity.

Diagnosis. Essentially clinical — asterixis, reversal of the sleep-wake cycle, disorientation, constructional apraxia and fetor hepaticus. A raised venous ammonia supports the diagnosis but does not confirm it; a normal ammonia makes HE unlikely, and levels should not be used to monitor treatment. Covert HE is detected with psychometric tests — the Animal Naming Test, PHES battery or Stroop smartphone app. Image the brain when the picture is atypical.

First-line treatment. Lactulose 30 mL two or three times daily, titrated to produce 2–3 soft stools per day; in comatose patients give as a retention enema (300 mL lactulose in 700 mL water). It acidifies the colon, converting absorbable ammonia to non-absorbable ammonium, and acts as an osmotic laxative. Monitor for dehydration, hypernatraemia and aspiration — over-treatment with lactulose can itself precipitate HE.

Second-line agents and adjuncts. Rifaximin 550 mg twice daily added to lactulose reduces recurrence and hospitalisation and is the agent of choice for secondary prophylaxis after a second episode of overt HE. Alternatives: L-ornithine L-aspartate, oral branched-chain amino acids, polyethylene glycol for rapid clearance, and zinc if deficient. Neomycin and metronidazole are effective but should be avoided long term in the elderly (ototoxicity, nephrotoxicity, neuropathy).

Nutrition and general care. Protein restriction is obsolete and harmful. Give 1.2–1.5 g/kg/day protein with 35 kcal/kg, favouring vegetable and dairy protein, in small frequent meals with a late evening snack to avoid overnight catabolism. Protect the airway and manage in ICU for grades III–IV; avoid benzodiazepines (flumazenil only for proven benzodiazepine ingestion); advise about driving and falls; consider TIPS reduction or occlusion or embolisation of large spontaneous shunts for recurrent HE; and refer for liver transplantation.

AASLD/EASL Practice Guidance (2022) and subsequent evidence — the treatment goal has shifted from clearing the acute episode to preventing recurrence, with lactulose plus rifaximin as standard secondary prophylaxis. Routine screening for covert HE is now recommended because it independently predicts falls, road traffic accidents, poor quality of life and progression to overt HE; and sarcopenia is recognised as an independent driver of HE (muscle is the main extra-hepatic site of ammonia detoxification), making nutritional therapy a specific treatment rather than merely supportive care. Faecal microbiota transplantation is promising but remains investigational.