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

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 established [21].

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 United States.

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 HE [19].

#### 7.4 Treatments on the horizon

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

Studies are currently underway comparing different formulations of rifaximin, evaluating the difference between the immediate release against the sustained extended release.

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

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 options especially in the setting of refractory HE.

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

### Ammonia DOI: http://dx.doi.org/10.5772/intechopen.88044

absorption and consequently indoxyl sulfate production [23] has been extrapolated to HE with promising results, but still in initial phases and further studies are needed to better characterize its role in the treatment of HE.
