Hepatic encephalopathy

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Hepatic encephalopathy ranges from subtle attention or psychomotor impairment to disorientation, stupor and coma. Overt disease is usually graded clinically with the West Haven framework: grade I includes altered attention or sleep pattern, grade II lethargy and disorientation with possible asterixis, grade III marked confusion or somnolence while responsive to stimuli, and grade IV coma. Grading is imperfect and inter-observer variation matters, so record concrete behaviour, orientation, Glasgow Coma Scale and airway protection rather than only a label.

An episode usually reflects interaction between impaired hepatic clearance or portosystemic shunting and a precipitant. Infection, spontaneous bacterial peritonitis, gastrointestinal blood in the bowel, constipation, renal dysfunction, excessive diuresis, vomiting, hyponatraemia or hypokalaemia, opioid or benzodiazepine exposure and recent TIPSS are high-yield causes. A patient can have more than one. Encephalopathy is therefore managed by simultaneous supportive care, systematic investigation and correction of triggers, not by laxative prescription alone.

After recovery, recurrence prevention includes a clear bowel plan, medication reconciliation, nutrition, alcohol support where relevant and rapid access for early cognitive change. Rifaximin is recommended by NICE within its marketing authorisation for reducing recurrence of overt episodes. Persistent disability despite apparently adequate therapy warrants specialist reassessment for an alternative neurological diagnosis, an unrecognised portosystemic shunt or advanced liver disease requiring transplant discussion.

Key points

Hepatic encephalopathy is a clinical neuropsychiatric syndrome caused by liver insufficiency or portosystemic shunting after competing explanations have been considered.
Asterixis supports metabolic encephalopathy but is neither specific to liver disease nor reliably present in deep coma.
Search actively for infection, gastrointestinal bleeding, constipation, dehydration, acute kidney injury, electrolyte disturbance and medicines that depress cognition.
A venous ammonia concentration does not confirm, exclude or grade overt encephalopathy; a normal result should prompt diagnostic reconsideration.
Lactulose is titrated to regular soft stools, not profuse diarrhoea, because over-treatment can worsen dehydration, hypokalaemia and encephalopathy.
Rifaximin is used with specialist oversight to reduce recurrent overt episodes, commonly alongside lactulose, rather than to replace precipitant treatment.
Avoid routine protein restriction; provide adequate energy and protein with dietetic help because sarcopenia reduces extrahepatic ammonia handling.
Recurrent or persistent encephalopathy should trigger review of adherence, constipation, sedating medicines, large spontaneous shunts, TIPSS and transplant suitability.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Liver failure or portosystemic shunting

Decompensated cirrhosis and large spontaneous or created shunts reduce hepatic clearance of gut-derived neuroactive substances before systemic circulation.

Inflammatory and gastrointestinal precipitants

Infection, gastrointestinal bleeding and constipation commonly increase toxin production or amplify brain vulnerability, often without a single dominant trigger.

Circulatory, metabolic and medicine triggers

Dehydration, acute kidney injury, electrolyte disturbance, sedatives and excess diuresis can precipitate or worsen cognitive dysfunction.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Neurotoxin accumulation
Ammonia and other gut-derived substances bypass or overwhelm hepatic detoxification and reach the systemic circulation and brain.
2
Astrocyte and neurotransmitter dysfunction
Intracerebral ammonia metabolism alters astrocyte volume, energy handling and inhibitory neurotransmission, impairing attention, behaviour and consciousness.
3
Inflammatory amplification
Systemic infection and cytokines increase blood-brain vulnerability and synergise with toxins, explaining deterioration despite an imperfect relationship with ammonia concentration.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Early behavioural change

Relatives may notice reversed sleep, slowed responses, irritability, poor handwriting or errors with familiar tasks before the patient recognises impairment. Establish the person's usual cognition and functional baseline.

Overt disorientationRed flag

Disorientation to time or place, inappropriate behaviour, lethargy and asterixis suggest overt encephalopathy, but fever, focal signs, head injury or meningism should redirect urgent investigation.

Threatened airwayRed flag

Marked somnolence, absent protective reflexes, recurrent vomiting or coma creates aspiration risk. Escalate early for airway protection and monitored care rather than repeatedly giving oral treatments.

Precipitant clues

Ask about melaena, haematemesis, fever, dysuria, abdominal pain, stool frequency, vomiting, diuretic changes, missed lactulose, alcohol, opioids, benzodiazepines and recent procedures.

Covert impairment

Difficulty driving, working or managing medicines without overt disorientation may reflect covert encephalopathy, but specialist psychometric assessment is needed because sleep disorders and depression can mimic it.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Bedside glucose and physiological observationsFirst step
Why
Detect immediately reversible coma and quantify acute physiological compromise.
Interpretation and limitations
Correct hypoglycaemia at once and investigate its cause. Hypoxia, hypotension, fever or hypothermia points toward systemic illness and determines the urgency of airway, sepsis and critical-care management.
02
FBC, renal profile, electrolytes and liver tests
Why
Find bleeding, infection, kidney injury and metabolic precipitants while defining hepatic reserve.
Interpretation and limitations
Falling haemoglobin, leucocytosis, rising creatinine, hyponatraemia or hypokalaemia can each precipitate deterioration. INR and bilirubin inform severity but do not prove that confusion is hepatic.
03
Cultures, chest assessment and diagnostic ascitic tap
Why
Identify occult infection, including spontaneous bacterial peritonitis, in decompensated cirrhosis.
Interpretation and limitations
Send blood and urine cultures when indicated and perform prompt paracentesis for new or worsening ascites or decompensation. An ascitic neutrophil count of at least 250 cells/mm³ supports SBP and requires immediate local-protocol therapy.
04
Venous or arterial ammonia
Why
Provide a contextual biochemical measurement when the diagnosis remains uncertain.
Interpretation and limitations
Values correlate poorly with clinical grade and handling errors are common. Do not use a raised result as proof; a normal result in apparent overt encephalopathy should make the team reconsider alternatives.
05
CT brain when clinically indicated
Why
Exclude haemorrhage, infarction, mass effect or injury when features are atypical.
Interpretation and limitations
Imaging is not mandatory for every familiar episode, but focal neurology, seizure, trauma, anticoagulation, severe headache or non-response lowers the threshold substantially.
06
Medication and toxicology review
Why
Identify prescribed, non-prescribed or withdrawal-related contributors to reduced consciousness.
Interpretation and limitations
Opioids, benzodiazepines, gabapentinoids, antihistamines and alcohol may amplify encephalopathy. Reversal agents require standard emergency indications and monitoring; an apparent response does not end the precipitant search.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Sepsis-associated delirium

Fever, hypotension, focal infection or inflammatory trajectory may explain confusion, though infection commonly precipitates true hepatic encephalopathy and both can coexist.

Alcohol withdrawal or Wernicke encephalopathy

Autonomic overactivity, tremor, hallucinations or nutritional ocular and gait signs require specific treatment rather than assuming every altered state is hepatic.

Intracranial or metabolic disease

Focal neurology, head injury, hypoglycaemia, hypercapnia, sodium disturbance or drug toxicity prompts urgent targeted testing and imaging.

Additional chapter-specific clues

Neurological alternativeRed flag

A focal deficit, unequal pupils, seizure, sudden severe headache, trauma or prolonged failure to improve is atypical and may justify urgent brain imaging or neurological review.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01StabiliseManage overt deteriorationFirst stepA person with cirrhosis or portosystemic shunting develops new disorientation, somnolence or coma.

1Perform ABCDE assessment, check glucose, record Glasgow Coma Scale and West Haven features, obtain intravenous access, and call for senior help if airway protection is doubtful.
2Stop or withhold non-essential sedatives and nephrotoxic or volume-depleting medicines while assessing bleeding, sepsis, renal injury, electrolyte imbalance and recent alcohol or drug exposure.
3AlternativeStart enteral lactulose when the airway and route are safe, using local guidance for an alternative route if swallowing is unsafe, while treating each identified precipitant in parallel.
4EscalationEscalate grade III–IV disease, shock, respiratory compromise, acute liver failure or failure to improve to critical care and the regional hepatology or transplant service.

02SearchFind the precipitantOvert encephalopathy is suspected, even when the presentation resembles previous episodes.

1Take a collateral history covering stools, bleeding, infection symptoms, intake, vomiting, diuretic use, medication adherence, recent TIPSS, constipation and psychoactive substances.
2Obtain targeted blood tests, cultures and imaging, and perform diagnostic paracentesis promptly when ascites is present because SBP can be clinically subtle.
3Reassess after initial treatment; persistent fever, focal signs, seizure or unexpectedly slow recovery requires renewed investigation rather than simply increasing laxative exposure.

03PreventReduce recurrent episodesThe patient has recovered from an overt episode or has repeated admissions.

1Agree an individual lactulose plan targeting two or three soft stools daily, explain how to respond to diarrhoea, and involve carers where capacity or memory is unreliable.
2After recurrent overt encephalopathy, discuss rifaximin through the liver service, reconcile interacting medicines and address nutrition, sarcopenia, constipation and alcohol-related needs.
3Review for large spontaneous shunts, post-TIPSS encephalopathy and transplant candidacy when recurrence continues despite adherence, and document driving and occupational advice appropriate to impairment.

Key medicines and prescribing safety2 treatments · regimens, roles and cautions

Reduces intestinal nitrogen absorption and is first-line enteral therapy for overt episodes and ongoing prevention when tolerated.

Lactulose oral solution

Initially 30–45 mL three or four times daily for hepatic encephalopathy, then adjust to produce two or three soft stools daily; follow the current SmPC and local acute pathway.

Protect the airway before oral administration. Excess dosing causes diarrhoea, dehydration, hypernatraemia or hypokalaemia; avoid in gastrointestinal obstruction or perforation and reassess abdominal distension or pain.

Reduces recurrence after overt episodes, usually as add-on therapy where lactulose is also being used and tolerated.

Rifaximin 550 mg tablets

Take 550 mg twice daily when prescribed by the specialist service to reduce recurrence of overt hepatic encephalopathy; review continued need and adherence according to the local pathway.

It is not rescue monotherapy for coma or untreated precipitants. Check the current SmPC for hypersensitivity, severe skin reactions, C. difficile diarrhoea, warfarin INR effects and important P-glycoprotein interactions.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Airway loss and aspiration

Progressive somnolence or coma removes airway protection, allowing gastric contents or blood to enter the lungs and cause respiratory failure.

Falls, injury and functional decline

Disorientation and impaired coordination cause trauma, driving restriction, dependence and loss of confidence even between overt episodes.

Recurrent decompensation

Repeated episodes increase admissions, malnutrition and caregiver burden and may signal a need for transplant assessment or shunt review.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Record consciousness, orientation, asterixis, respiratory status and bowel output frequently during an acute episode, with closer monitoring as clinical grade increases.
Trend renal function, sodium, potassium, glucose, haemoglobin and infection markers while correcting the precipitant and avoiding iatrogenic volume depletion.
Review lactulose effect by stool consistency and frequency rather than by ammonia concentration, and reduce it if diarrhoea or dehydration develops.
After discharge, document recurrence, adherence, constipation, weight, muscle loss, driving implications and the patient's or carer's early-warning plan.
For rifaximin, monitor clinical recurrence and treatment tolerance; use additional laboratory monitoring where interacting medicines or comorbidity requires it.
Escalate repeated admissions or persistent cognitive impairment for specialist shunt, TIPSS and transplant assessment rather than accepting progressive disability as inevitable.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Ammonia is contextual

Ammonia participates in pathophysiology, but its circulating concentration is affected by sampling and overlaps substantially between clinical grades; examine the patient and search for triggers.

Blood becomes substrate

An upper gastrointestinal bleed delivers a large nitrogen load into the bowel, so occult bleeding may present as encephalopathy before dramatic haematemesis is seen.

Muscle protects cognition

Skeletal muscle metabolises ammonia; malnutrition and sarcopenia therefore increase vulnerability and explain why indiscriminate protein restriction can be counterproductive.

Asterixis is not exclusive

Negative myoclonus can appear in uraemia, respiratory failure and drug toxicity, so it supports a metabolic process without identifying its cause.

Carers detect recurrence

A relative may recognise sleep reversal or task errors earlier than the patient, making collateral history and a written escalation plan valuable safety interventions.

11Common pitfallsFrequent interpretation and management errors.

01
Calling any confusion in cirrhosis hepatic encephalopathy before checking glucose, oxygenation, infection, drugs, trauma and focal neurology.
02
Using a raised ammonia result to end diagnostic reasoning or repeating ammonia to judge response to treatment.
03
Giving oral lactulose to a deeply drowsy patient without first addressing airway and aspiration risk.
04
Escalating lactulose through watery diarrhoea and thereby worsening volume depletion, potassium loss and renal dysfunction.
05
Prescribing rifaximin while leaving constipation, bleeding, sedatives or infection untreated.
06
Restricting dietary protein routinely instead of obtaining specialist nutritional assessment and protecting muscle mass.