ORIGINAL PAPER Disaccharides in the treatment of hepatic encephalopathy Praveen Sharma & Barjesh Chander Sharma Received: 24 December 2012 / Accepted: 20 February 2013 / Published online: 2 March 2013 # Springer Science+Business Media New York 2013 Abstract Management of hepatic encephalopathy (HE) pri- marily involves avoidance of precipitating factors and ad- ministration of various ammonia-lowering therapies such as nonabsorbable disaccharides and antimicrobial agents like rifaximin. The nonabsorbable disaccharides which include lactulose and lactitol are considered the first-line therapy for the treatment of HE and minimal hepatic encephalopathy (MHE). Lactulose significantly improves cognitive function and health-related quality of life in patients with MHE. Lactitol is comparable to lactulose in the treatment of HE with fewer side effects. Lactulose has also shown to be effective in primary and secondary prophylaxis of HE. Disaccharides were found to be comparable to rifaximin in recent systemic reviews in the treatment of HE however conclusion was based on inclusion of some poor quality trials. Combination therapy of disaccharides either with rifaximin, L-ornithine L-aspartate,probiotics for the treat- ment of HE needs further validation in large studies. Keywords Hepatic encephalopathy . Disaccharides . Lactulose Introduction Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome, which may complicate acute or chronic liver fail- ure. It is characterized by changes in mental state including a wide range of neuropsychiatric symptoms ranging from minor signs of altered brain function to deep coma. The West Haven Criteria are most often used to grade HE, with scores ranging from I-IV (IV being coma). However, it is a challenge to diagnose patients with minimal hepatic encephalopathy (MHE) or grade 1 HE; so it might be practical to combine these entities and name them covert HE for clinical use (Ferenci et al. 2002; Riordan and Williams 1997; Bajaj et al. 2009a, b). Even in MHE without obvious clinical symptoms, neuropsychological and neurophysiological testing uncovers deficits which impact on the quality of life and the fitness to drive a motor vehicle (Bajaj et al. 2007, 2009a, b; Groeneweg et al. 1998). One of the major tenets of the pathophysiology of HE is hyperammonemia that results from an increased nitrogenous load from the gastrointestinal tract. Ammonia is produced both by bacterial degradation of amines, aminoacids, pu- rines, and urea as well as enterocytic glutaminase activity that converts glutamine to glutamate and ammonia (Albrecht et al. 2010; Bismuth et al. 2011). Astrocytes play an important role in the pathogenesis of HE with conse- quences for neuronal function. Astrocytes have the ability to eliminate ammonia by the synthesis of glutamine through amidation of glutamate by the enzyme glutamine synthetase Hyperammonemia leads to the accumulation of glutamine within astrocytes, which exerts an osmotic stress that causes astrocytes to take in water and swell (Lockwood et al. 1991, Haussinger et al. 2000). Therapy for hepatic encephalopathy and role of non-absorbable disaccharides The first step in treatment of HE is identifying and treating precipitating causes which includes management of hypovolemia, gastrointestinal bleeding, infection, excessive di- uretic use, diarrhea, vomiting, hyponatremia, hypokalemia or P. Sharma : B. C. Sharma (*) Department of Gastroenterology, G.B.Pant Hospital, Academic Block Room - 203, New Delhi, India e-mail: drbcsharma@hotmail.com Metab Brain Dis (2013) 28:313–320 DOI 10.1007/s11011-013-9392-4