8. Conclusions

the intestinal absorption of carbohydrates and glucose and results in their enhanced delivery to the colon. As a result, the ratio of saccharolytic to proteolytic bacterial flora is increased and blood ammonia levels are decreased. A randomized controlled double-blind crossover trial has demonstrated that acarbose improves mild hepatic encephalopathy in patients with cirrhosis and adult-onset diabetes mellitus. Similarly, probiotic regimens (such as Lactobacillus SF68) have been used to modify intestinal flora and diminish ammonia generation. Several studies have suggested that these agents may be beneficial in humans with mild encephalopathy. A Cochrane Database review in 2011 was unable to conclude that probiotics improve

7.3 Metabolic removal of ammonia: ornithine-aspartate (ornithinetranscarbamylase/zinc), sodium benzoate (phenylbutyrate,

Sodium benzoate, sodium phenylbutyrate, and sodium phenylacetate, all of which increase ammonia excretion in urine, are approved by the FDA for the treatment of hyperammonemia resulting from urea cycle enzyme defects and may improve HE in patients with cirrhosis. Administration of sodium benzoate, however, results in a high sodium load, and the efficacy of this agent is not clearly

Administration of zinc, which has been used because zinc deficiency is common in patients with cirrhosis. Furthermore, because it increases the activity of ornithine transcarbamylase, an enzyme in the urea cycle, it may also improve HE; however, clear efficacy has not been established. L-ornithine–l-aspartate (LOLA), a salt of the amino acids ornithine and aspartic acid that activates the urea cycle and enhances ammonia clearance, has been shown in several randomized controlled studies to improve HE compared with lactulose; however, this agent is not available in the

Extracorporeal albumin dialysis using the molecular adsorbent recirculating system (MARS) has resulted in a reduction in blood ammonia levels and improvement in severe encephalopathy in patients with acute-on-chronic liver failure. Further studies are needed to clarify whether albumin dialysis has a role in treatment of

Fecal microbiota transplant is being studied prospectively in a few centers in North America. As an established treatment in C. difficile colitis, this treatment aims

Studies are currently underway comparing different formulations of rifaximin,

Other antibiotics, cheaper and with safer profiles are being studied prospectively to compare with the current gold standard, rifaximin. One such antibiotic notably is

Data regarding dialysis as a treatment modality has not been satisfactory in order to justify its regular use in the setting of HE. There are prospective studies evaluating other exchange therapies such as plasmapheresis as viable alternative treatment

AST-120, an oral spherical carbonaceous adsorbent approved and used in chronic kidney disease to decrease uremia by decreasing intestinal indole

to modify the intestinal flora, as it happens with use of antibiotics, such as

evaluating the difference between the immediate release against the sustained

clinically relevant outcomes [19].

Liver Disease and Surgery

phenylacetate), and dialysis

established [21].

United States.

HE [19].

rifaximin.

extended release.

nitazoxanide.

32

7.4 Treatments on the horizon

options especially in the setting of refractory HE.

Our understanding of the interactive physiology between ammonia and HE has greatly increased since its first proposition by Hippocrates of Kos B.C. and its first description in 1860 by von Frerichs [22]. There are multiple effective treatments available and yet others in the horizon. However, there is still much more to be understood about the role of ammonia in HE and other factors may still be involved in the pathophysiology of portosystemic encephalopathy. The future of HE appears bright and future treatment options will hopefully improve the quality of life of patients with this potentially debilitating disease.
