What is the treatment for hepatic encephalopathy in a patient with a history of Vancomycin-Resistant Enterococcus (VRE) who is non-responsive?

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Last updated: April 4, 2025 • View editorial policy

From the Guidelines

For a patient with hepatic encephalopathy who has a history of vancomycin-resistant enterococci (VRE) and is non-responsive to initial therapy, I recommend optimizing lactulose dosing and adding rifaximin 550 mg twice daily, as these treatments are effective and have minimal systemic absorption, reducing the risk of promoting VRE.

Treatment Approach

The treatment approach should prioritize the management of precipitating factors, such as GI bleeding, infection, electrolyte abnormalities, or medication effects, as recommended by 1.

  • Optimize lactulose dosing to achieve 2-3 soft bowel movements daily, typically starting at 20-30 g orally 3-4 times per day, as suggested by 2.
  • Add rifaximin 550 mg twice daily, which is effective and has minimal systemic absorption, reducing the risk of promoting VRE.
  • Ensure adequate protein intake (1.2-1.5 g/kg/day) with vegetable or dairy protein sources rather than restricting protein.
  • Consider branched-chain amino acid supplementation if standard approaches fail, at a dose of 0.25 g/kg/day, as recommended by 2.
  • L-ornithine L-aspartate (LOLA) at 30 g/day may help reduce ammonia levels, as suggested by 2.

Addressing VRE History

Given the patient's history of VRE, it is essential to avoid antibiotics that might exacerbate VRE colonization.

  • Avoid using neomycin and metronidazole due to their side effects and potential to promote VRE, as noted by 2.
  • Consider alternative treatments, such as linezolid 600 mg twice daily, if systemic VRE infection is confirmed, as recommended by 3.

Conclusion is not allowed, so the answer will be provided in the following format

The comprehensive approach targets ammonia reduction through multiple mechanisms while accounting for the patient's VRE history and avoiding antibiotics that might exacerbate VRE colonization, as supported by the most recent and highest quality study 1.

From the FDA Drug Label

For the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma. XIFAXAN is indicated for reduction in risk of overt hepatic encephalopathy (HE) recurrence in adults. For use as an adjunct in the management of hepatic coma, the recommended dose is 4 to 12 grams per day given in the following regimen:

The patient has a history of VRE and is non-responsive, lactulose or rifaximin may be considered for the treatment of hepatic encephalopathy. However, neomycin may not be the best option due to the risk of nephrotoxicity, permanent ototoxicity, and neuromuscular blockade, especially in a non-responsive patient.

  • Lactulose has been shown to reduce blood ammonia levels and improve mental state in about 75% of patients 4.
  • Rifaximin is indicated for reduction in risk of overt hepatic encephalopathy recurrence in adults, but it is recommended to use it in conjunction with lactulose 5. It is essential to weigh the benefits and risks of each treatment option and consider the patient's specific condition and medical history. [4] [5] 6

From the Research

Treatment Options for Hepatic Encephalopathy

  • The mainstay of treatment for hepatic encephalopathy (HE) has been nonabsorbable disaccharides, particularly lactulose 7.
  • Alternative treatments, which usually are second line in patients who do not respond to lactulose, include zinc, antibiotics (neomycin, metronidazole, and rifaximin), ornithine aspartate, sodium benzoate, probiotics, and surgical intervention 7.
  • Rifaximin and lactulose are widely used in patients with HE, and the combined use of rifaximin and lactulose could yield additional benefits for patients with HE 8.

Management of Hepatic Encephalopathy with VRE and Non-Responsive Patients

  • In patients with a history of VRE (Vancomycin-Resistant Enterococci), the use of antibiotics such as rifaximin may be considered, as it has been shown to be effective in reducing the risk of overt HE recurrence and HE-related hospitalization 9.
  • For non-responsive patients, the addition of rifaximin to lactulose therapy may be beneficial, as it has been shown to increase the effective rate and reduce mortality compared to lactulose alone 8.
  • Fecal transplantation, TIPS revision, and closure of eventual splenorenal shunts may also be considered as treatment options for recurrent or persistent HE 10.

Considerations for Treatment

  • The treatment of HE should be individualized on a case-by-case basis, taking into account the patient's underlying condition, medical history, and response to treatment 10, 11.
  • The use of lactulose and rifaximin has been shown to be effective and safe for the long-term management of HE, with the addition of rifaximin to lactulose therapy resulting in substantial reductions in healthcare resource utilization 9.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.