Vol. 10 Issue S2
On the cover: Official Journal of the Mexican Association of Hepatology and the Latin-American Association for the Study of the Liver. Annual Meeting Mexican Association of Hepatology. Workshop of Advances in Ammonia Metabolism and Hepatic Encephalopathy.
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome characterized by changes in cognitive function, behavior, and personality, as well as by transient neurological symptoms and electroencephalographic changes, which occur in the context of acute or chronic liver failure. Cirrhosis is the main disease associated to HE, and it is known that its incidence is increasing worldwide. As a cause of mortality, cirrhosis is ranked 14 worldwide, but 10 in developed countries. It has been demonstrated that the incidence of liver disease is increasing, in part because of the ascending prevalence of NAFLD, HCV, HCC, as well of alcohol consumption. The real incidence of cirrhosis in Latin America is unknown, although in some Latin American countries that provided national data, cirrhosis death rates were between 5 and 17/100,000 for men and 3 and 5/100,000 for women. Disability, quality of life, and social aspects should be considered when assessing the impact of a disease. In this context, preliminary estimates of the global burden of disease attributable to chronic liver disease seem to be substantial. Hepatic encephalopathy, a main complication of liver failure, occurs in 30-45% of patients as overt encephalopathy, but when subclinical or minimal hepatic encephalopathy (MHE) is considered, estimates of the incidence of encephalopathy vary from 20 to 60%. In USA, the 2009 NIH Report on the Costs of Digestive Diseases stated that liver disease was the second most costly disease in direct and indirect costs (13.1 billion dollars). Although the economic cost of HE has not been assessed, it is obvious that the economic impact of HE on daily activities of living is extremely high, as the costs of diminished work performance and lost wages are substantial.
Hepatic encephalopathy (HE) is a heterogeneous disease that develops as a result of serious liver disease, such as in fulminant hepatitis or cirrhosis, or a portosystemic shunt. It manifests as a spectrum of abnormalities involving cognition, attention, functional ability, personality and intellect. The neuropsychiatric impairment associated with HE can range from mild alteration of cognition and consciousness to coma, depending on the stage of the illness. In 1998, the World Gastroenterology Organization formed a working party to develop guidelines and recommendations for the diagnosis, grading and treatment of HE for research and practice. In this report, we discuss the various tests available for diagnosis and grading and the recommendations of the working party, which provide a framework for further studies on clinical trial methodology.
Background. Minimal hepatic encephalopathy (MHE) has implications for health-related quality of life as well as for survival of cirrhotic patients, but a standardized diagnostic test is not available. Objective. To determine the prevalence of MHE among cirrhotic patients by using the psychometric hepatic encephalopathy score (PHES) system and the critical flicker frequency (CFF) test to diagnose MHE and to identify factors that influence the results of these tests. Material and methods. From April 2007 to March 2008, PHES and CFF tests were performed on patients with cirrhosis but no overt hepatic encephalopathy. Descriptive statistics were used to express the results and the Spearman correlation was used to evaluate CFF and PHES results according to age and education level. Results. We studied 104 patients. The prevalence of MHE was 55.8% (n = 58) based on a positive result for either the PHES or the CFF test, 32.7% (n = 34) based on positive PHES results alone, 34.6% (n = 36) based on positive CFF test results alone and 11.5% (n = 12) based on a positive result for both tests. According to PHES, the incidence of MHE was correlated with education level (r = 0.333, p = 0.001), but not with age. According to CFF, the incidence of MHE was correlated with age (r = -0.93, p = 0.049), but not with education level. Conclusion. The prevalence of MHE was similar to that previously reported. Patient literacy influences MHE diagnosis with PHES but not with CFF. CFF is a simple and feasible method that identifies patients with MHE who may benefit from treatment independently of their education level.
The prevalence of under nutrition in cirrhotic patients is 61% and it usually progresses as the disease becomes more advanced. The deterioration in the nutritional status and its associated metabolic derangements has raised doubts about the benefits of severe and prolonged protein restriction as a treatment for hepatic encephalopathy. However, the practice of dietary protein restriction for patients with liver cirrhosis is deeply embedded among medical practitioners and dietitians. To date, no solid conclusions may be drawn about the benefit of protein restriction. However, the negative effects of protein restriction are clear, that is, increased protein catabolism, the release of amino acids from the muscle, and possible worsening of hepatic encephalopathy. In conclusion, chronic protein restriction causes progressive and harmful protein depletion and must be avoided.
The term minimal hepatic encephalopathy (MHE) refers to the subtle changes in cognitive function, electrophysiological parameters, cerebral neurochemical/neurotransmitter homeostasis, cerebral blood flow, metabolism, and fluid homeostasis that can be observed in patients with cirrhosis who have no clinical evidence of hepatic encephalopathy; the prevalence is as high as 84% in patients with hepatic cirrhosis. Physician does generally not perceive cirrhosis complications, and neuropsychological tests and another especial measurement like evoked potentials and image studies like positron emission tomography can only make diagnosis. Diagnosis of minimal hepatic encephalopathy may have prognostic and therapeutic implications in cirrhotic patients. The present review pretends to explore the clinic, therapeutic, diagnosis and prognostic aspects of this complication.
Hyperammonemia and associated cerebral edema cause neurological abnormalities in liver disease patients. Although only 15% of ammonia production originates in the colon, management strategies for hepatic encephalopathy (HE) have focused on reducing ammonia generation from the bowel rather than on manipulating systemic mechanisms involved in ammonia metabolism. Administration of L-ornithine L-aspartate (LOLA) improves mental status and decreases serum and spinal fluid ammonia levels by stimulating both the urea cycle and glutamine (Gln) synthesis, which are key metabolic pathways in ammonia detoxification. LOLA was shown to be superior to a placebo for management of HE, and the results of several clinical trials suggest that its effectiveness could be higher with the more severe grades of this syndrome. Compared with the standard treatment, LOLA is effective not only in reducing hyperammonemia and the severity of this disease, but also in improving the patient's perceived quality of life. Therefore, LOLA is a promising alternative for the management of HE.
By the end of the nineteenth century, ammonia had been identified as the main factor responsible for hepatic encephalopathy syndrome. Ammonia is one of the principal products of hepatic metabolism and high concentrations are toxic to the body. Under physiological conditions, the main way by which the body restricts the blood concentration of ammonia to a nontoxic level is by converting it to urea in the liver via the Krebs cycle. The synthesis of glutamine represents an alternative pathway for ammonia detoxification in cirrhotic patients. Although high concentrations of ammonia have been strongly associated with brain edema, estimates of the strength of the correlation between serum ammonia levels and the severity of hepatic encephalopathy vary. The accuracy of ammonia assays depends on the site of specimen collection, treatment of the specimen and the analytical method used. New methods involving measurement of the partial pressure of ammonia and new noninvasive techniques involving quantification of ammonium in the breath have been described. The purpose of this review is to identify factors that affect serum ammonia levels, from its origin and metabolism to its analysis and interpretation of results in the laboratory. In conclusion, variations in estimates of serum ammonia level and the severity of hepatic encephalopathy arise because of individual differences in ammonia metabolism and differences in the accuracy of analytical methods.
Introduction. Hepatic encephalopathy (HE) refers to a complex neuropsychiatric syndrome that is progressive but potentially reversible and may have a significant impact on quality of life, as it is characterized by alterations in cognitive function, behavior and personality as well as transient neurological symptoms and electroencephalographic abnormalities. Objective. The aim of this study was to evaluate scientific evidence for the effectiveness and safety of LOLA infusions for treatment of clinical hepatic encephalopathy in patients with chronic liver disease. Material and methods. We included all randomized, controlled, double-blind, and humans' studies that were published in indexed journals. Results. Were identified 48 references (17 using PubMed, 12 using Medline and 19 using the Cochrane database). Of these, six were selected as having met the inclusion criteria. A total of 623 patients were randomized in these publications. Conclusion. The available scientific evidence supports the adoption of LOLA infusion as a treatment for clinical encephalopathy in patients with liver failure, because it has been shown to improve neuropsychiatric status and decrease serum levels of ammonia with a low incidence of adverse effects (less than 5%).
Acute, acute-on-chronic and chronic liver diseases are major health issues worldwide, and most cases end with the need for liver transplantation. Up to 90% of the patients die waiting for an organ to be transplanted. Hepatic encephalopathy is a common neuropsychiatric syndrome that usually accompanies liver failure and impacts greatly on the quality of life. The molecular adsorbent recirculating system (MARS) is a recently developed form of artificial liver support that functions on a base of albumin dialysis. It facilitates the dialysis of albumin-bound and water-soluble toxins, allowing the patient to survive and even improving some clinical features of liver failure. The following manuscript reviews the technical features of MARS operation and some of the clinical trials that analyze the efficacy of the system in the therapy of liver diseases.