Nitazoxanide Plus Lactulose Versus Lactulose Alone Treatment of Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a reversible neuropsychiatric syndrome associated with chronic and acute liver dysfunction. It is characterized by cognitive and motor deficits of varying severity.

Hepatic encephalopathy is caused by accumulation of nitrogenous substances, primarily ammonia, in the blood. In advanced stages it is referred to as hepatic coma which may be preceded by seizures. The treatment goal is to reduce nitrogen load from the GI tract and to improve central nervous system (CNS) status.

Treatment options include lactulose administered orally or by nasogastric tube or enema, non-absorbable antibiotics, and protein-restricted diets.

Lactulose is nonabsorbable disaccharides that are currently used as first line agents for the treatment of HE. Its action is thought to beconversion to lactic acid and acetic acid resulting in acidification of the gut lumen. This favors conversion of ammonia (NH3) to ammonium (NH4+), which is relatively membrane impermeable, and inhibits ammoniagenic coliform bacteria.

Nitazoxanide is an oral agent indicated for the treatment of infectious diarrhea caused by Crytpsporidiumparvum and Giardia lamblia. Basu and colleagues presented a pilot prospective study at the 2008 American Association for the Study of Liver Diseases meeting showing clinical improvement in HE among cirrhotic patients who received nitazoxanide and lactulose.

Mantry and colleagues showed that the number of hospitalizations and the duration of hospital stays were shortened for patients receiving combination therapy compared with those receiving lactulose monotherapy.