Secondary Prophylaxis of Overt Hepatic Encephalopathy in Cirrhosis: a Randomized Controlled Trial of Colistin Versus Lactulose

Hepatic encephalopathy (HE) is a reversible neuropsychiatric changes, it occurs in 30%-45% of cirrhotic patients during their life. Once HE is developed, the 1-year mortality exceeds 60%. The high morbidity and mortality combined with the costs underline the importance of effective treatment and prevention of HE.

The exact pathogenesis of HE is still unknown but ammonia is known to play a key role. Strategies to prevent and treat HE aims at reducing the production and absorption of gut derived neurotoxins, particularly ammonia, mainly through bowel cleansing, non absorbable disaccharides and non -absorbable antibiotics.

Patients with previous episode of overt HE, have a 40% cumulative risk of recurrence at 1 year. Because recurrent episodes of HE are associated with increased health care burden, poor prognosis, and risk of death, prevention of the recurrence of HE should be considered in each patient.

After an episode of overt HE has resolved, patients with cirrhosis should receive secondary prophylactic therapy for an indefinite period of time or until they undergo liver transplantation. Lactulose is considered the first line for secondary prophylaxis of overt HE while rifaximin is add-on therapy to lactulose.

Non-absorbable disaccharides like lactulose acts as both osmotic laxative, and gut acidifying agent reducing the production and the absorption of ammonia from the intestines by changing the gut microbiota. However, side effects of lactulose therapy including excessively sweet taste and gastrointestinal side effects such as abdominal pain, bloating, flatulence, severe and unpredictable diarrhea possibly leading to dehydration result in frequent non-adherence in clinical practice. Lactulose non-adherence, reported as a factor in 39% of hospital admissions, was the single most frequent precipitant of overt HE .