There is currently no curative treatment for hepatic encephalopathy, except liver transplantation, a heavy surgery. The current therapeutic solutions are mainly aimed at reducing symptoms to improve the quality of life of patients or allow them to wait to receive a new liver.
The most widely known pathogenic factor is ammonia, most therapeutic options are aimed at decreasing its production or promoting its removal.
We are working actively to test some new molecules under research and development with our bile-duct ligation model.
Lactulose (galactose and fructose) is an artificial form of sugar that is not absorbed into your body (meaning, it does not enter the blood stream). Lactulose creates a hostile environment for the “bad” bacteria in the intestine, therefore lowering ammonia production in the intestine. Transformed into acetic acid and lactic acid, thus decreasing the intestinal pH, it promotes the growth of non-ammoniegenic bacteria. Moreover, by its cathartic (purgatory) effect, it reduces the absorption of ammonia and explaining why it may also be used to treat constipation. Like any medication, lactulose can have side effects, including nausea, gas, abdominal cramps and diarrhea and some people may not be able to tolerate lactulose over a long period of time.
Targeting intestinal bacteria generating ammonia, several antibiotics have been tested to date in patients with liver disease. Metronidazole and rifaximin are antibiotics that may be used to control the growth of bacteria in the intestine, including bacteria which produce ammonia. Rifaximin is a semi-synthetic antibiotic working by preventing the synthesis of RNA and bacterial proteins. Due to its pyridoimidazole ring, itis very poorly absorbed into the body which helps it concentrate in the intestines, where it can reduce the growth of unfriendly bacteria.
Probiotics or friendly bacteria can change the balance of bacteria in the intestines, increasing the proportion of friendly bacteria. The strategy is to alter the microbial population by promoting non-ammoniegenic bacteria. This can result in decreased levels of ammonia production and other toxic substances. However, the challenge of finding the right strains and standardized dosages remains to be met to treat patients with liver disease.
Branched-chain amino acids
Branched-chain amino acids (Isoleucine, Leucine and Valine) can help maintain muscle mass and increase ammonia clearance (primarily through the muscle).
The ultimate treatment for HE is to replace the damaged liver with a healthy donor liver. Most of the time patients who receive a liver transplant improve their brain function. However, it is important to control and prevent episodes of OHE as much as possible because numerous episodes of OHE can possibly lead to permanent (and therefore irreversible) brain damage. For this reason, it is extremely important to take care of the brain during illness.
Christopher F. Rose (2012) Ammonia-Lowering Strategies for the Treatment of Hepatic Encephalopathy. Clin Pharmacol Ther, 92: 321-331. doi: 10.1038/clpt.2012.112