What is it

HE is a decline in brain function that occurs in patients with liver cirrhosis. The underlying cause of HE; liver cirrhosis, is caused by repeated and long-term liver damage, which causes liver cells to die and scar tissue to form, and liver function to become increasingly impaired.  

The reduced liver function, which means that toxins such as ammonia, which are normally removed from the body by the liver, build up in the blood and reach the brain. Combined with the inflamed liver it causes a neuroinflammation and as a consequence a broad spectrum of cognitive and motor impairments  as well as sleep  disturbances. 

 High alcohol consumption, viruses (such as hepatitis C and B) and the storage of too much fat in the liver are common causes of cirrhosis. 

HE is classified into two broad categories based on severity, covert hepatic encephalopathy (CHE) and overt hepatic encephalopathy (OHE).


The clinical presentation of HE may be highly variable and may range from barely noticeable symptoms to confusion and coma. In addition, HE also causes poor health-related quality of life, frequent hospitalisations, and a higher risk of road accidents and falls which, in turn, also means that HE patients place a significant burden on care providers.   

CHE is the milder stage of HE, in which a person’s ability to perform daily tasks is affected, resulting in poor quality of life. The symptoms may include mild confusion, short attention span, forgetfulness, mood swings, change in sleep patterns and slurred speech. In addition, CHE increases the risk of OHE episodes, which makes prevention of OHE at this stage important.  

OHE is a more severe stage of HE and is characterised by the person experiencing impaired cognitive and neuromotor function with symptoms such as severe disorientation regarding time and place, marked confusion, extreme sleepiness and jumbled, slurred speech that can’t be understood. In the most severe form of HE, people can become unresponsive, unconscious and enter a coma. More than 50 percent of the patients who develop an OHE episode are hospitalised. More than one-third of these patients are readmitted to hospital within one month. 

Therapeutic goals

Umecrine Cognition intends to address two of the most important unmet needs with golexanolone:  

  • Currently available treatment reduces, but do not eliminate, the risk of recurrent OHE episodes. As a result, there is still a major unmet need for new treatments that can further reduce the risk of a new episode and thereby reduce hospital admissions and progression of the cognitive impairment that worsens with each new episode of OHE. 
  • Treatment that can address the cognitive impairment and sleep disturbances experienced by both CHE and OHE patients is still a major unmet need. Despite the severity of the cognitive deficits, excessive sleepiness and the subsequent poor quality of life as well as increased risk of OHE, there is still no approved treatment for these symptoms.  


In 2020 there was an estimated 340 00 patients diagnosed with HE in the 7 major pharmaceutical markets (7MM).   

In the US, HE accounted for approximately 100,000 hospitalisations annually between 2005 and 2009, with a mortality rate of 14–16% for the five-year period.  In 2014, the estimated cost of hospitalisations for HE patients in the US was USD 11.9 billion. 

Current treatments

Currently, there is no approved therapy available for the treatment of HE; one drug, rifaximin, is approved in the US and EU to prevent the recurrence of OHE. Several novel therapies are in development for the disease. Of these seven, golexanolone is the only drug candidate with a direct effect in the CNS. The primary effect of the others is to reduce ammonia levels.