Evolving Concepts: The Negative Effect of Minimal Hepatic Encephalopathy and Role for Prophylaxis in Patients With Cirrhosis

• Published in: Clinical therapeutics 2013-09, Vol.35 (9), p.1458-1473
• Main Authors: Prakash, Ravi K., MD, MRCP, Kanna, Sowjanya, MD, Mullen, Kevin D., MD, FRCPI
• Format: Article
• Language: English
• Subjects: Anti-Infective Agents - therapeutic use; Attention Deficit Hyperactivity Disorder; Biological and medical sciences; Brain research; cirrhosis; Clinical medicine; Clinical Trials as Topic; Family medical history; Gastroenterology. Liver. Pancreas. Abdomen; Gastrointestinal Agents - therapeutic use; Gastrointestinal Tract - microbiology; hepatic encephalopathy; Hepatic Encephalopathy - diagnosis; Hepatic Encephalopathy - drug therapy; Hepatic Encephalopathy - etiology; Hepatic Encephalopathy - prevention & control; Humans; Internal Medicine; lactulose; Lactulose - therapeutic use; Liver cirrhosis; Liver Cirrhosis - complications; Liver Cirrhosis - physiopathology; Liver diseases; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical Education; Medical sciences; minimal; Other diseases. Semiology; overt; Pathogenesis; Pharmacology. Drug treatments; probiotics; Probiotics - therapeutic use; Quality of Life; Rifamycins - therapeutic use; rifaximin; Toxins
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2013.07.421

Abstract Background Hepatic encephalopathy (HE), which may be categorized as minimal or overt, is a serious and progressive neuropsychiatric condition that occurs in patients with liver disease or portosystemic shunting. Overt HE (OHE) presents as a wide spectrum of clinical signs and symptoms, ranging in severity from mild confusion to life-threatening coma. Minimal HE (MHE) is a more subtle form of the condition; it is characterized by deficits in cognitive function in patients with a normal clinical examination. Objective The purpose was to review the effect of MHE on patients and caregivers, as well as its currently available diagnostic and treatment options. Methods A MEDLINE search of published diagnostic assessments, clinical trials, and guidelines from 1985 to 2012 were reviewed and analyzed to assess the potential effect of MHE in the clinical practice setting. Results Accumulating evidence suggests that MHE has a substantial negative effect on patient quality of life, particularly in activities that require attention, motor skills, and visuospatial ability. Because MHE lacks obvious clinical signs, specialized testing is required for diagnosis, although there is no consensus on the most appropriate assessment tools or treatment algorithms. Compounds derived from bacterial activities in the gut can cause neurochemical changes in the brain. These gut-derived toxins (eg, ammonia, benzodiazepine-like substances) are implicated in the pathophysiology of OHE. In patients with liver disease or portosystemic shunting, these toxins are inefficiently detoxified, accumulate in the blood, cross the blood-brain barrier, and result in abnormalities such as altered neurotransmission, astrocyte swelling, and impaired energy metabolism. Therefore, treatments have focused on toxin removal and the management of gut flora levels. Several studies have indicated that probiotics, nonabsorbable disaccharides, and nonsystemic antibiotics can all be effective in improving the symptoms of MHE. Furthermore, prophylaxis for MHE in patients with cirrhosis could serve to improve patient quality of life while preventing its transition to OHE. Conclusions Although MHE detection and treatment is not currently the standard of care, several therapies have been reported to improve cognitive function and quality of life. Interest is increasing in the proactive diagnosis and management of MHE in the clinical practice setting. However, research is required to determine the conditions u