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Management of hepatic encephalopathy in primary care

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Group members:

  • Michelle Clayton (Chair, lecturer in liver care)
  • Dr Richard Aspinall (consultant hepatologist)
  • Dr Honor Merriman (general practitioner)
  • Dr John O’Malley (general practitioner with special interest in gastroenterology)

Algorithm for the management of hepatic encephalopathy in primary care

*Summary of product characteristics can be found at www.medicines.org.uk/emc
Grading of symptoms is detailed overleaf

Algorithm for the management of hepatic hencephalopathy in primary care

Hepatic encephalopathy (HE)

  • HE is a frequent complication of chronic liver disease and one of its most debilitating manifestations, severely affecting the lives of patients and their carers and increasing demand on the healthcare system2
  • It is a reversible condition caused by accumulation of toxins normally removed by the liver, such as ammonia3
  • HE has a wide spectrum of neurological and psychiatric manifestations, ranging from subclinical alterations to coma (see Table 1)2

Table 1: Possible symptoms of HE2

Symptom grade   Symptom description
Covert Minimal
  • psycometric or neuropsychological alterations on tests without clinical evidence of mental change
Grade 1
  • trivial lack of awareness
  • euphoria or anxiety
  • shortened attention span
  • impairment of addition and subtraction
  • altered sleep rhythm
Overt Grade 2
  • lethargy or apathy
  • disorientation
  • obvious personality change
  • inappropriate behaviour
  • dyspraxia
  • asterixis
Grade 3
  • somnolence to semi-stupor
  • impaired responsiveness to stimuli
  • confusion
  • gross disorientation
  • bizarre behaviour
Grade 4
  • coma

Pharmacological management

  • Once any precipitating causes have been addressed, treatment aims to minimise the production and absorption of toxins (such as ammonia) in order to reduce symptoms4
  • Medication is usually initiated in secondary care at the time of diagnosis, but primary care may need to prescribe repeat doses in line with local arrangements
  • Prescription of CNS-altering drugs and sedatives should be avoided in patients with HE
  • Check summary of product characteristics before prescribing to rule out contraindications, precautions, and potential drug interactions
  • Treatment of overt HE:
    • lactulose: 
      • non-absorbable polysaccharide that changes the pH of stools to prevent growth of bacteria that produce toxins, such as ammonia4
      • starting dose of 30–50 ml 3 times daily; dose should be titrated to achieve 2–3 soft stools per day4
      • if lactulose does not result in 2–3 soft stools per day do not substitute with laxatives, as it is not the laxative effect that is useful in the treatment of HE
  • Prevention of recurrent episodes of overt HE:
    • lactulose:
      • if lactulose does not result in 2–3 soft stools per day contact a specialist for guidance on management, such as using rifaximin-α therapy, which is usually initiated in secondary or tertiary care
    • non-absorbable antibiotics:
      • rifaximin-α:
        • is licensed for the reduction in recurrence of episodes of overt HE in patients ≥18 years of age5
        • minimises the bacterial load in the gut, which reduces the production of ammonia and other compounds implicated in the pathogenesis of HE5
        • may be prescribed in combination with lactulose
        • recommended dose of 550 mg twice a day with or without food5

Monitoring

  • Monitor patients in line with local arrangements with specialist care
    • Urea and electrolytes should be monitored closely, especially in patients taking diuretics:
      • diuretics can cause hyponatraemia, hypokalaemia, or renal dysfunction, which are all triggers for HE

Safety

  • For full details of possible adverse reactions please refer to summaries of product characteristics at www.medicines.org.uk/emc
  • lactulose—common adverse reactions include flatulence, abdominal pain, nausea, and vomiting. If the dose is too high, diarrhoea will occur4
  • rifaximin-α—common adverse reactions reported with rifaximin-α are dizziness, headache, depression, dyspnoea, upper abdominal pain, abdominal distension, diarrhoea, nausea, vomiting, ascites, rashes, pruritus, muscle spasms, arthralgia and peripheral oedema5

Conflicts of interest

Michelle Clayton has received honoraria, and travel and accommodation expenses from Norgine Pharmaceuticals Ltd for presenting at conferences and participating in advisory boards.

Richard Aspinall has received honoraria, and travel and accommodation expenses from Norgine Pharmaceuticals Ltd for presenting at conferences and participating in advisory boards.

Honor Merriman has previously received honoraria for participating in the developement of a Guidelines algorithm, sponsored by Roche Diagnostics Ltd.

John O’Malley has received honoraria, and travel and accommodation expenses from Actavis UK Ltd, Norgine Pharmaceuticals Ltd, and Reckitt Benckiser Healthcare Ltd for presenting at conferences and participating in advisory boards.

References

  1. DVLA. Drug or alcohol misuse or dependence: assessing fitness to drive. DVLA, 2019. Available at www.gov.uk/guidance/drug-or-alcohol-misuse-or-dependence-assessing-fitness-to-drive
  2. Vilstrup H, Amodio P, Bajaj J et al. Hepatology 2014; 60: 715–735.
  3. Guest J, Nanuwa K, Barden R. Health Qual Life Outcomes 2014; 12: 89–97.
  4. Intrapharm Laboratories Limited. LactugalSummary of Product Characteristics. Available at www.medicines.org.uk/emc
  5. Norgine Pharmaceuticals Limited. Targaxan 550 mg film-coated tablets—­Summary of Product Characteristics. Available at www.medicines.org.uk/emc

 

This supplement has been sponsored and commissioned by Norgine Pharmaceuticals Limited. Norgine Pharmaceuticals Limited was able to suggest relevant experts to Chair the group, with final decisions on the remaining group members resting with the Chair and Guidelines. Norgine Pharmaceuticals Limited has reviewed the supplement for technical and scientific accuracy, and to ensure its compliance with appropriate regulations. Final editorial control has remained with the contributors and Guidelines. The views and opinions of the contributors expressed in this document are not necessarily those of Norgine Pharmaceuticals Limited, or of Guidelines, its publishers, advisers, or advertisers.

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Date of preparation: February 2020

 

 

Best practice in liver care