From the Guidelines
The management of hepatic encephalopathy should prioritize the use of non-absorbable disaccharides, such as lactulose, as first-line treatment, with the addition of rifaximin for patients with recurrent episodes or inadequate response to lactulose alone, as recommended by the most recent guidelines 1. The treatment protocol for hepatic encephalopathy involves a multi-faceted approach targeting ammonia reduction and addressing precipitating factors.
Key Components of Treatment
- First-line treatment with lactulose, administered at 20-30 g orally 3-4 times per day, with the goal of achieving at least 2 bowel movements per day, and then titrating the dose to achieve 2-3 soft stools per day 1.
- Addition of rifaximin 400 mg three times/day or 550 mg twice/day for patients with recurrent episodes or those who don't respond adequately to lactulose alone 1.
- Identification and treatment of precipitating factors such as GI bleeding, infection, electrolyte abnormalities, constipation, or medication non-compliance.
- Ensuring adequate protein intake (1.2-1.5 g/kg/day) rather than restricting protein.
- Consideration of branched-chain amino acids, zinc supplementation, or L-ornithine L-aspartate for severe or refractory cases.
Prevention of Recurrence
- Use of non-absorbable disaccharides (lactulose or lactitol) to prevent recurrence of hepatic encephalopathy in patients with cirrhosis, with a strong agreement grade of 1+ 1.
- Addition of rifaximin to prevent recurrence in cases of failed prevention with non-absorbable disaccharides, with a strong agreement grade of 2+ 1.
- Offering a therapeutic education program to the patient and caregiver to improve quality of life and limit hospitalizations, based on expert opinion and strong agreement 1.
From the FDA Drug Label
The efficacy of XIFAXAN 550 mg taken orally two times a day was evaluated in a randomized, placebo-controlled, double-blind, multi-center 6-month trial of adult subjects from the U.S., Canada, and Russia who were defined as being in remission (Conn score of 0 or 1) from hepatic encephalopathy (HE).
Breakthrough overt HE episodes were experienced by 31 of 140 subjects (22%) in the XIFAXAN group and by 73 of 159 subjects (46%) in the placebo group during the 6-month treatment period.
Comparison of Kaplan-Meier estimates of event-free curves showed XIFAXAN significantly reduced the risk of HE breakthrough by 58% during the 6-month treatment period.
HE-related hospitalizations (hospitalizations directly resulting from HE, or hospitalizations complicated by HE) were reported for 19 of 140 subjects (14%) and 36 of 159 subjects (23%) in the XIFAXAN (rifaximin) and placebo groups, respectively
Comparison of Kaplan-Meier estimates of event-free curves showed XIFAXAN significantly reduced the risk of HE-related hospitalizations by 50% during the 6-month treatment period.
The Hepatic Encephalopathy protocol involves the use of rifaximin (XIFAXAN) 550 mg taken orally two times a day, which has been shown to significantly reduce the risk of HE breakthrough by 58% and HE-related hospitalizations by 50% during a 6-month treatment period 2.
- Key points:
- Rifaximin is used in patients who are in remission from hepatic encephalopathy.
- The treatment effect of rifaximin is consistent across different demographic and baseline characteristics.
- Lactulose was concomitantly used by 91% of the patients in the study, and it is also used for the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma 3.
- Main considerations:
- Rifaximin has been shown to be effective in reducing the risk of HE breakthrough and HE-related hospitalizations.
- The use of lactulose in combination with rifaximin may be considered in the treatment of hepatic encephalopathy.
From the Research
Hepatic Encephalopathy Management
The management of hepatic encephalopathy involves several key steps, including:
- Stabilization of the patient
- Addressing modifiable precipitating factors
- Lowering blood ammonia levels
- Managing elevated intracranial pressure (ICP) if present
- Managing complications of liver failure that can contribute to encephalopathy, such as hyponatremia 4
Treatment Options
Treatment options for hepatic encephalopathy include:
- Lactulose and rifaximin, which remain a mainstay of therapy for patients with chronic hepatic encephalopathy 4
- Non-absorbable disaccharides, such as lactulose, which can help reduce ammonia production and absorption 5
- Oral antibiotics, such as rifaximin, which can help reduce the production and absorption of gut-derived neurotoxic substances, including ammonia 5
- Polyethylene glycol, which can be used in combination with rifaximin or lactulose to help manage symptoms 6
Combination Therapy
The use of combination therapy with rifaximin and lactulose has been shown to be effective in managing hepatic encephalopathy, with some studies suggesting that it can provide additional benefits in terms of increased effective rate and decreased mortality compared to lactulose alone 7. However, other studies have found that lactulose alone may be sufficient for some patients, particularly those with lower grades of encephalopathy 8
Reversible Causes
It is essential to identify and manage reversible causes of hepatic encephalopathy, such as:
- Increased ammonia production and/or decreased clearance (e.g. infection, GI bleed, constipation, hypokalemia, dehydration) 4
- Ionic disorders, such as hyponatremia, which should be managed with gradual sodium correction to avoid central myelinolysis syndrome 4
Emerging Therapies
Many emerging therapies, both pharmacologic and interventional, are currently being studied to improve the management of hepatic encephalopathy, including new antibiotics and other treatments aimed at reducing ammonia production and absorption 4