Management of hepatic encephalopathy

Seek expert advice.

Management of HE differ according to its type and severity.

• patients with covert HE usually do not require treatment except in cases where the condition is thought to be adversely affecting quality of life
• once grade 3 or 4 encephalopathy develops, there is a high risk of cerebral oedema and multiorgan failure.

Appropriate treatment overt HE will result in shorter episodes and will also prevent further episodes

The primary objectives of treatment are to: (1)

• Provide supportive care
• Exclude other causes of altered mental status
• Identify and correct precipitating factors
• Reduce the nitrogenous load from the gut
• Assess the need for long-term therapy.

• the first step in management of acute patients is to address underlying precipitants of encephalopathy - such as hypoglycaemia, hypoxia, haemorrhage, sepsis, drug toxicity, or electrolyte disturbance, should be corrected. (1)

Nutrition:

• although dietary protein withdrawal is advised, one randomised controlled trial found no increased risk of HE with a normal-protein diet, compared with a low-protein diet (2), and protein malnutrition may contribute to sarcopenia, potentially worsening the condition.
• the International Society for Hepatic Encephalopathy and Nitrogen Metabolism recommends that 1.2-1.5 g/kg of protein can be given in small meals distributed throughout the day, with a late night snack of complex carbohydrates
• nasogastric tube feeding should be considered if above dietary target cannot be achieved

Non-absorbable disaccharides and probiotics

• Lactulose (a non-absorbable disaccharide) helps in reducing pH and excretion of ammonia as well as the utilisation of ammonia in the metabolism of gut bacteria (3)
  • EASL-AASLD guidelines recommends that lactulose should be used as the first line agent in the management of overt HE and then to continue in order to prevent further episodes (3)
  • dose - 25 mL of lactulose twice daily aiming to achieve three soft bowel motions a day
• probiotic therapy
  • has been shown to decrease overt hepatic encephalopathy
  • can be given as yoghurt drinks or tablets, commonly containing Lactobacillus rhamnosus and and Saccharomyces boulardii
• polyethylene glycol
  • has been shown to be as effective as, and possibly superior to, lactulose in terms of speed of resolution of hepatic encephalopathy and reduction in length of hospital stay (4)

Neomycin and rifaximin

• neomycin
  • was the first antibiotic agent to be widely used in HE
  • is not used routinely in clinical practice because of the significant toxicity associated with its long-term use
• rifaximin (5)
  • is recommended, within its marketing authorisation, as an option for reducing the recurrence of episodes of overt hepatic encephalopathy in people aged 18 years or older
  • a semi-synthetic derivative of the antibiotic rifamycin
  • one systematic review and meta-analysis reported that rifaximin has a beneficial effect on mortality and full recovery from HE compared with placebo, non-absorbable disaccharides, or other antibiotics (6)
  • decreases intestinal production and absorption of ammonia, which is thought to be responsible for the neurocognitive symptoms of hepatic encephalopathy, thereby delaying the recurrence of acute episodes (1,2)

Sedation should be avoided so that there is no masking of the level of consciousness.

Appropriate candidates should be referred to liver transplant centres for evaluation after a first episode of HE, and those with end-stage liver disease and recurrent or persistent HE not responding to other treatments should be considered for transplantation. (3)

References:

1. Bajaj JS, O'Leary JG, Lai JC, et al. Acute-on-chronic liver failure clinical guidelines. Am J Gastroenterol. 2022 Feb 1;117(2):225-52.
2. Córdoba J, López-Hellín J, Planas M, et al. Normal protein diet for episodic hepatic encephalopathy: results of a randomized study. J Hepatol. 2004 Jul;41(1):38-43.
3. European Association for the Study of the Liver. EASL clinical practice guidelines on the management of hepatic encephalopathy. J Hepatol. 2022 Sep;77(3):807-24.
4. Hoilat G et al. Polyethylene glycol versus lactulose in the treatment of hepatic encephalopathy: a systematic review and meta-analysis. BMJ Open Gastroenterology 2021. Vol.8, Issue1.
5. NICE (March 2015). Rifaximin for preventing episodes of overt hepatic encephalopathy
6. Kimer N, Krag A, Møller S, et al. Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy. Aliment Pharmacol Ther. 2014 Jul;40(2):123-32.