7.2 Inhibiting ammonia production: antibiotics (neomycin, paromomycin, metronidazole, rifaximin, and vancomycin), laxatives (disaccharideslactulose/lactitol, polyethylene glycol), and modification of flora (Lactobacillus SF68, acarbose)

The use of laxatives, especially non-absorbable disaccharides, has been the cornerstone of the treatment HE. Oral lactulose or lactitol (the latter is not available in the United States) are thought to have an in vitro benefit over other laxatives. This is due their multi-mechanistic properties. Not only do they cause catharsis but they convert ammonia to ammonium and also reduce intestinal pH, thereby reducing ammonia absorption. These agents improve symptoms in patients with acute and chronic encephalopathy when compared with placebo but do not improve psychometric test performance or mortality. Side effects are common and include abdominal cramping, bloating, flatulence, and electrolyte imbalance.

Oral antibiotics have been used with the aim of modifying the intestinal flora and lowering stool pH to enhance the excretion of ammonia. Antibiotics are generally used as second-line agents after lactulose or in patients who are intolerant of non-absorbable disaccharides. Rifaximin given orally in a dose of 550 mg twice daily was approved in 2010 for the treatment of chronic hepatic encephalopathy and reduction in the risk of recurrence of overt encephalopathy in patients with advanced liver disease. The tolerability and side-effect profile of rifaximin are superior to those of lactulose, albeit at greater financial cost. Other antibiotics, including neomycin, paromomycin, metronidazole, and vancomycin, have been studied in small trials and case series, but some may have an increased side effect profile and the effectiveness of others are not well established.

Agents that may modify intestinal flora and modulate the generation or intestinal absorption of ammonia have been evaluated as potential treatments. Acarbose, an intestinal α-glucosidase inhibitor used to treat type 2 diabetes mellitus, inhibits

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 clinically relevant outcomes [19].

absorption and consequently indoxyl sulfate production [23] has been extrapolated to HE with promising results, but still in initial phases and further studies are

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

needed to better characterize its role in the treatment of HE.

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

patients with this potentially debilitating disease.

The authors declare no conflict of interest.

Appendices and nomenclature

LOLA l-ornithine–l-aspartate

BCAAs branched-chain amino acids

EDTA ethylenediaminetetraacetic acid FMT fecal microbiota transplant HE hepatic encephalopathy

Edwin Jin Su Lee and Jonathan C. Huang\* University of Rochester, Rochester, NY, USA

provided the original work is properly cited.

\*Address all correspondence to: jonathan\_huang@urmc.rochester.edu

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

HHT hereditary hemorrhagic telangiectasia

MARS molecular adsorbent recirculating system pNH3 partial pressure of gaseous ammonia PSE portosystemic encephalopathy

8. Conclusions

Ammonia

Conflict of interest

BC before Christ

Author details

33
