**5. Future research**

Glutaminase plays a major role in the cause of hepatic encephalopathy. However, a prospective study is required to evaluate the clinical utility of the genetic marker we have identified for predicting overt hepatic encephalopathy before it can be recommended for clinical practice.

In the gut, intestinal glutaminase activity is increased in patients with cirrhosis and correlates with minimal hepatic encephalopathy (Romero-Gomez, Ramos-Guerrero et al. 2004). Glutaminase is also a key factor in the brain. Glutamine synthesis detoxifies ammonia in the brain, but glutaminase transforms glutamine into ammonia, glutamate, and free radicals in the mitochondria, and these byproducts are implicated in mitochondria dysfunction and further neurotransmission impairment (Trojan horse hypothesis) (Albrecht and Norenberg 2006).

Studies to date have indicated that OP is safe and patient studies in minimal HE and HE are needed to establish whether OP or glutaminase inhibitors such TPHD-17 (a promising GA inhibitor) could be used as a treatment for this significant complication of liver disease.
