Avoiding the use of sedative or narcotic agents is important. Opiates are particularly problematic as they potentiate constipation and, therefore, must be used at the lowest possible dose with appropriate laxatives prescribed concomitantly. Non-absorbable disaccharides, particularly lactulose, form the mainstay of first-line treatment.
Efficacy is based around the ability to reduce intestinal production and absorption of ammonia, which is achieved by a combination of actions: laxative effect, increased bacterial uptake of ammonia via intraluminal pH change , inhibition of glutaminase activity resulting in a reduction of intestinal ammonia production, and an effect on the gut microbiome [6].
A Cochrane review found a clear preventive effect with non-absorbable disaccharides against development and recurrence of overt hepatic encephalopathy [6]. As a result, lactulose remains standard medical therapy. The recommended starting dose for lactulose is 25 mL every 12 h until at least two soft bowel motions are produced per day. Dose reduction should be performed as required, with titration to a level that maintains two to three bowel motions per day [1].
Non-adherence can be a contributing factor to treatment failure. Therefore, patients and their carers should be given clear advice on how to titrate the lactulose dose to maximize efficacy and reduce side-effects. If individuals are intolerant of lactulose, they should use alternative laxatives or regular enemas, although these will have less impact on ammonia production than lactulose.
Rifaximin is a minimally absorbed oral antibiotic that alters the gut flora, leading to reduced ammonia production and absorption. It is concentrated in the gastrointestinal tract, and despite broad-spectrum activity against gram-positive and gram-negative enteric bacteria, it has a low risk of inducing bacterial resistance [7].
Rifaximin maintained remission from hepatic encephalopathy in a landmark randomized controlled trial of patients [7]. This treatment also significantly reduced the risk of hospitalization for those with overt hepatic encephalopathy over 6 months.
Of note, Another study demonstrated long-term safety with rifaximin and a sustained reduction in hepatic-encephalopathy-related and all-cause hospitalization [8]. At present, rifaximin is recommended by the National Institute for Health and Care Excellence to prevent recurrence of over hepatic encephalopathy. In practice, treatment with rifaximin should be considered in patients with persistent symptoms of encephalopathy despite lactulose or in lactulose-intolerant patients, or in those who have had two or more episodes of over hepatic encephalopathy in the previous 6 months.
Rifaximin and lactulose in combination controls hepatic encephalopathy in most patients. Education of patients with overt hepatic encephalopathy and of their relatives or carers is paramount to reducing recurrence and hospital admissions. Understanding of hepatic encephalopathy is limited among many of those affected and their caregivers, leading to structured education tools being developed with promising initial results [10].
Key education points include the effects of medication and potential side-effects, the importance of adherence, and early signs of recurrence and appropriate actions eg, laxative administration or, if febrile, seeing a general practitioner or attending hospital. Other therapies for hepatic encephalopathy are generally less robustly supported by the available evidence, but could be considered in patients with recurrent disease despite lactulose and rifaximin, particularly for those who do not have the option of liver transplantation.
L-ornithine-aspartate is a stable salt of the amino acids ornithine and aspartic acid that is thought to lower blood ammonia concentrations in patients with cirrhosis by stimulating urea and glutamine synthesis from hepatocytes and skeletal muscle respectively.
It might also have a directly hepatoprotective effect [11]. It can be administered orally or intravenously. A recent Cochrane review suggested that L-ornithine-aspartate has beneficial effects on mortality and hepatic encephalopathy, but the quality of evidence remains very low [12].
Supplementation with branched-chain amino acids is another potential option. Levels of these amino acids are reduced in patients with cirrhosis, which results in impaired conversion of ammonia to glutamine in skeletal muscle and reduces its detoxification. Oral supplementation is effective in treating overt hepatic encephalopathy compared with placebo or no intervention, but not compared to lactulose or neomycin [13].
There are no trials examining the efficacy of this treatment in prevention of recurrent hepatic encephalopathy. Some patients with recurrent severe hepatic encephalopathy have large dominant portosystemic shunts that increase the risk of this disease due to gut-derived toxins bypassing the liver and entering the systemic circulation.
Encephalopathy is most commonly a complication of cirrhosis but can also occur in some other conditions. How is hepatic encephalopathy treated? Lactulose The toxins that enter the brain are byproducts of the foods we eat and are also produced by the normal bacteria in the large intestine. Thus treatment is aimed at decreasing the amount of toxins that can be absorbed from the large intestine. Lactulose brand names include Constulose, Enulose, Generlac and Kristalose alters the acidity in the colon which prevent absorption of ammonia, one of the toxins.
The correct dose of lactulose varies from one person to the next and it may change from day to day for each individual.
The correct dose will cause 3 to 4 loose bowel movements per day. This effect is most prominent in patients who have not responded adequately to lactulose alone.
At this point, the other antibiotics studied do not appear to have additive effects with lactulose. Abstract Lactulose is the most frequently utilized agent in the treatment of hepatic encephalopathy because of its efficacy and the fact that it has few serious side effects.
Publication types Review.
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