Norgine_CMYK

This management algorithm has been commissioned and funded by Norgine Pharmaceuticals Limited and developed in partnership with Guidelines. See below for full disclaimer. 

Final version - HE algorithm

Information intended for UK healthcare professionals only.

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Group members: Michelle Clayton (Chair), Dr Richard Aspinall, Dr Honor Merriman, Dr Jez Thompson

Hepatic encephalopathy (HE) 

  • HE is a frequent complication of liver disease and one of its most debilitating manifestations1
    • it is a reversible condition caused by accumulation of toxins normally removed by the liver, such as ammonia
    • it has a wide spectrum of neurological and psychiatric manifestations, ranging from subclinical alterations to coma (Table 1)1
  • HE is an uncommon but important condition
    • HE severely affects the lives of patients and their carers1
    • HE increases demand on the healthcare system1
    • early identification of HE in primary care can make a difference to patient outcomes
  • Clinicians should have a high index of suspicion for HE in patients with known cirrhosis or risk factors for development of liver disease (Box 1) and who present with the symptoms in Table 1. 

Box 1

Table 1

Identification and management of HE in primary care 

  • Figure 1 summarises the expert group’s recommendations for identification and management of HE in primary care.

Merged figure 1

Assessment

  • Have a high index of suspicion for HE in a patient with cirrhosis or risk factors for liver disease (Box 1) who presents with symptoms or signs associated with HE (Table 1)
  • Make the most effective assessment of the patient you can using telephone, video, or face-to-face contact
    • assess severity of disease based on presenting symptoms and signs (Table 1)
    • administer simple assessment tools to assess the patient’s status (e.g. animal naming test3,4 see Box 2)
  • Seek advice from or refer to a liver specialist for early outpatient review if minimal or Grade 1 symptoms
    • consider starting lactulose5 depending on waiting times (see ‘Initial treatment’)
  • Arrange hospital admission for Grade 2–4 symptoms
  • Arrange early specialist review in patients with previously stable cirrhosis who have an episode of HE, as this indicates decompensation.

Box 2

Administration

  • If diagnosis confirmed by specialist, add appropriate code to the patient’s notes (e.g. code 13920009 in SNOMEDCT)
  • Arrange for electronic alert to be added to surgery system for all patients at risk of HE, e.g. those with established cirrhosis.

Education

  • Educate the patient, family, and carers (who may identify the signs earliest) at every opportunity: 
    • signs and symptoms of HE (Table 1)
    • precipitating factors (Box 3)
    • safety risks (Box 4)

Box 3

Box 4

  • Direct the patient to useful resources (Box 5) and useful support contacts as per local protocols.

Box 5

Pharmacological management

  • Once any precipitating factors have been addressed (Box 3), treatment aims to minimise the production and absorption of toxins (such as ammonia) in order to reduce symptoms5,7
  • Sedating drugs, including opioid analgesics, should be prescribed with caution in patients with HE
  • Box 6 summarises treatments for HE.

Box 6

Initial treatment of HE 

  • Lactulose5
    • primary care clinicians may consider starting lactulose while the patient waits for specialist assessment, depending on waiting time 
      • starting dose of 30–45 ml (6–9 x 5 ml spoonfuls) or 2–3 sachets 3–4 times daily
      • patients may adjust their maintenance dose to 15–30 ml (corresponding to 1–2 sachets) to achieve 2–3 soft stools each day5
    • if lactulose does not result in 2–3 soft stools per day:
      • do not substitute with other laxatives, as it is not the laxative effect that is useful in the treatment of HE
      • contact a specialist for guidance on management, such as using rifaximin-α, which is an amber drug usually initiated in secondary or tertiary care (see ‘Treatment for recurrent episodes of overt HE’ and Box 6)
    • common adverse reactions of lactulose include flatulence, abdominal pain, nausea, and vomiting. If the dose is too high, diarrhoea may occur5
      • for full details of possible adverse reactions please refer to summary of product characteristics for lactulose at www.medicines.org.uk/emc or British National Formulary (BNF).5,8

Treatment for recurrent episodes of overt HE

  • Continue lactulose5
  • Rifaximin-α7
    • typically initiated in secondary or tertiary care
    • primary care may need to prescribe taking local arrangements into consideration
    • recommended dose for HE is 550 mg twice a day7
    • common adverse reactions are dizziness, headache, depression, dyspnoea, upper abdominal pain, abdominal distension, diarrhoea, nausea, vomiting, ascites, rashes, pruritis, muscle spasms, arthralgia, and peripheral oedema7
      • for full details of possible adverse reactions please refer to summary of product characteristics for rifaximin-α at www.medicines.org.uk/emc or British National Formulary (BNF).7,8

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

Practice points

  • Box 7 provides some practice points of which to be aware.

Box 7

References

  1. Vilstrup H, Amodio P, Bajaj J et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology 2014; 60: 715–735.
  2. Guest J, Nanuwa K, Barden R. Utility values for specific hepatic encephalopathy health states elicited from the general public in the United Kingdom. Health Qual Life Outcomes 2014; 12: 89–97.
  3. Agarwal A, Taneja S, Chopra M, et al. Animal naming test—a simple and accurate test for diagnosis of minimal hepatic encephalopathy and prediction of overt hepatic encephalopathy. Clin Exp Hepatol 2020; 6: 116–224.
  4. Campagna F, Montagnese S, Ridola L et al. The animal naming test: An easy tool for the assessment of hepatic encephalopathy. Hepatology 2017; 66: 198–208.
  5. Mylan Products Ltd. Duphalac (lactulose) 3.335 g/5 ml oral solution—summary of product characteristics. Available at www.medicines.org.uk/emc/
  6. DVLA. Drug or alcohol misuse or dependence: assessing fitness to drive. DVLA, 2021. Available at www.gov.uk/guidance/drug-or-alcohol-misuse-or-dependence-assessing-fitness-to-drive
  7. Norgine Limited. TARGAXAN® (rifaximin-α)—summary of product characteristics. Available at www.medicines.org.uk/emc/
  8. NICE. British National Formulary. Available at: https://bnf.nice.org.uk (accessed 2 July 2021).
  9. Yeoman A, Aspinall R, Clayton M, Johnson J. Consensus statement: identification and management of hepatic encephalopathy. Guidelines in Practice, 2021. Available at www.guidelinesinpractice.co.uk/455680.article

This management algorithm has been commissioned and funded by Norgine Pharmaceuticals Limited and developed in partnership with Guidelines. Norgine Pharmaceuticals Limited reviewed and approved the contributor brief, suggested a Chair and experts for the group, and carried out full medical approval on all materials to ensure compliance with regulations. The sponsorship fee included honoraria for the participants. The views and opinions of the participants are not necessarily those of Guidelines, its publisher, advisers, or advertisers. No part of this publication may be reproduced in any form without the permission of the publisher.

Group members—Michelle Clayton (Chair, Liver Nurse Educator, St James’s University Hospital, Leeds), Dr Richard Aspinall (Consultant Hepatologist, Portsmouth Liver Centre), Dr Honor Merriman (GP, NHS Oxfordshire), Dr Jez Thompson (GP, The Garden Surgery, Leeds)

Conflicts of interest—The group members received an honorarium from Norgine Pharmaceuticals Limited to develop this algorithm. Michelle Clayton is a member of the SLIDE committee, which is a Norgine initiative.

 

UNITED KINGDOM
Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk/. Adverse events should also be reported to Medical Information at Norgine Pharmaceuticals Ltd on: Tel. +44 (0)1895 826 606 Email. medinfo@norgine.com

UK-HEP-XIF-2100039

Date of preparation: October 2021