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The AASLD/EASL Practice Guideline Subcommittee on Hepatic Encephalopathy are: Jayant A. Talwalkar (Chair, AASLD), Hari S. Conjeevaram, Michael Porayko, Raphael B. Merriman, Peter L.M. Jansen, and Fabien Zoulim. This guideline has been approved by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver and represents the position of both associations. These recommendations provide a data-supported approach. They are based on the following: (1) formal review and analysis of the recently published world literature on the topic; (2) guideline policies covered by the American Association for the Study of Liver Diseases/European Association for the Study of the Liver (AASLD/EASL) Policy on the Joint Development and Use of Practice Guidelines; and (3) the experience of the authors in the specified topic. Intended for use by physicians, these recommendations suggest preferred approaches to the diagnostic, therapeutic, and preventive aspects of care. They are intended to be flexible, in contrast to standards of care, which are inflexible policies to be followed in every case. Specific recommendations are based on relevant published information. To more fully characterize the available evidence supporting the recommendations, the AASLD/EASL Practice Guidelines Subcommittee has adopted the classification used by the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) workgroup, with minor modifications (Table 1). The classifications and recommendations are based on three categories: the source of evidence in levels I through III; the quality of evidence designated by high (A), moderate (B), or low quality (C); and the strength of recommendations classified as strong (1) or weak (2). The literature databases and search strategies are outlined below. The resulting literature database was available to all members of the writing group (i.e., the authors). They selected references within their field of expertise and experience and graded the references according to the GRADE system.1 The selection of references for the guideline was based on a validation of the appropriateness of the study design for the stated purpose, a relevant number of patients under study, and confidence in the participating centers and authors. References on original data were preferred and those that were found unsatisfactory in any of these respects were excluded from further evaluation. There may be limitations in this approach when recommendations are needed on rare problems or problems on which scant original data are available. In such cases, it may be necessary to rely on less-qualified references with a low grading. As a result of the important changes in the treatment of complications of cirrhosis (renal failure, infections, and variceal bleeding [VB]), studies performed more than 30 years ago have generally not been considered for these guidelines. Hepatic encephalopathy (HE) is a frequent complication and one of the most debilitating manifestations of liver disease, severely affecting the lives of patients and their caregivers. Furthermore, cognitive impairment associated with cirrhosis results in utilization of more health care resources in adults than other manifestations of liver disease.2 Progress in the area has been hindered by the complex pathogenesis that is not yet fully elucidated. Apart from such biological factors, there remains the larger obstacle that there are no universally accepted standards for the definition, diagnosis, classification, or treatment of HE, mostly as a result of insufficient clinical studies and standardized definitions. Clinical management tends to be dependent on local standards and personal views. This is an unfavorable situation for patients and contrasts with the severity of the condition and the high level of standardization in other complications of cirrhosis. The lack of consistency in the nomenclature and general standards renders comparisons among studies and patient populations difficult, introduces bias, and hinders progress in clinical research for HE. The latest attempts to standardize the nomenclature were published in 2002 and suggestions for the design of HE trials in 2011. Because there is an unmet need for recommendations on the clinical management of HE, the EASL and the AASLD jointly agreed to create these practice guidelines. It is beyond the scope of these guidelines to elaborate on the theories of pathogenesis of HE, as well as the management of encephalopathy resulting from acute liver failure (ALF), which has been published as guidelines recently. Rather, its aim is to present standardized terminology and recommendations to all health care workers who have patients with HE, regardless of their medical discipline, and focus on adult patients with chronic liver disease (CLD), which is, by far, the most frequent scenario. As these guidelines on HE were created, the authors found a limited amount of high-quality evidence to extract from the existing literature. There are many reasons for this; the elusive character of HE is among them, as well as the lack of generally accepted and utilized terms for description and categorization of HE. This makes a practice guideline all the more necessary for future improvement of clinical studies and, subsequently, the quality of management of patients with HE. With the existing body of evidence, these guidelines encompass the authors' best, carefully considered opinions. Although not all readers may necessarily agree with all aspects of the guidelines, their creation and adherence to them is the best way forward, with future adjustments when there is emergence of new evidence. Advanced liver disease and portosystemic shunting (PSS), far from being an isolated disorder of the liver, have well-known consequences on the body and, notably, on brain functioning. The alterations of brain functioning, which can produce behavioral, cognitive, and motor effects, were termed portosystemic encephalopathy (PSE)3 and later included in the term HE.4 Unless the underlying liver disease is successfully treated, HE is associated with poor survival and a high risk of recurrence.5, 6 Even in its mildest form, HE reduces health-related quality of life and is a risk factor for bouts of severe HE.7-9 Hepatic encephalopathy is a brain dysfunction caused by liver it as a of or from alterations to This definition, in with is based on the that are of brain and that the a to liver The and of HE are to the severity of the underlying liver and In patients with fully HE is an that the of the disease, such as or encephalopathy is in cirrhosis with The of HE may not be an clinical and there are used for its which the in the and The of the of of cirrhosis is in in those with and in patients with portosystemic The that in of those with cirrhosis their clinical and in the in most HE or HE in of patients with The of HE in is not well The risk for the of is within years cirrhosis diagnosis, on the of risk factors, such as other complications to cirrhosis or infections, or and and with a of were found to have a risk of and with have a risk of within 6 Even with cirrhosis and cognitive dysfunction or one of years of the of is and is by the patient selection data were by It an of the frequent of the health care by patients with HE that for in the in the European are not these are to be Furthermore, the of and cirrhosis is and more be to further the of HE. Hepatic encephalopathy a of and In its HE and as well as and other brain As HE such as and may be by the and alterations in and motor of the with are of the is may to and and acute with or and, The for Hepatic Encephalopathy and the of or as the of In patients with HE, motor such as and a can be In may and in can be can are in such as and of and with are in the of to or or is present in the to of HE that or and is, in not a a of of It is by that such as of the with or the of the can be in other such as the and is not of HE it can be in other the cognitive or and motor of HE may not be or not progress in in in the severity of HE. Hepatic is a of HE to by severe motor the of with and of with and or alterations have been and not to may with liver HE may present with with in which brain brain This condition was a term considered this is to and may be more than in patients with liver disease, in of Apart from these manifestations of HE, it is accepted in clinical practice that all of HE and their manifestations are and this is a for treatment research on HE patients and on patients of bouts of on the from those to other may and are later under of may be associated with in and Hepatic encephalopathy be classified according to all of the to the underlying disease, HE is to the severity of The that is HE has been clinical and research a of such is (Table classifications that to aim and and be used to its HE is to the of factors, HE is for standards and expertise lack of or of or or for to to classification, according to or not the patient has liver failure has recently been Although the and this classification is a research The the of of HE in a patient with severe liver who not have of brain The of for HE and the of HE. 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The term and HE. strategies can be and Because the condition of cognitive functioning, which may not be to the the the use of on the local and and with one of the being more accepted as to as a for and is important it can poor quality of life and and patients and the The of and in patients with to be as high as every patient risk be this may be and the consequences of the are not and treatment is not approach may be to patients who have problems with their quality of life or in there are from the patients and their for or HE patients risk for Furthermore, of the available are for the and it is important to patients who not have factors, such as or be by a to that the the result is (i.e., for or in 6 has been of or not that the is a are not to to and are not in the best of both the patient and the local the of patients with HE on the consequences of their and, the is to the have the patient for In cases, the with the that have the expertise to and the to the Although the have been used to for and there is, most a poor them HE is a is with and it is HE a in the of these and of the results for further management need an of the and on the of HE are the of or by of the and one of the following: or or or In the clinical or may use for the severity of HE with which are that data are available and the have been for use in this patient levels not any diagnostic, or in HE patients with in an level is in a patient with and it is the of HE is in of may be to the There may be to which be is in or the relevant be are be when standards for or or other not or information. the risk of is in this patient and the may be a brain is of the of HE and on clinical of other Hepatic encephalopathy be as a from cognitive with through 1). The of HE is through of other of brain dysfunction 1). Hepatic encephalopathy be of the of and the need for care 1). encephalopathy is by clinical and can be graded according the and the 1). The and of and can be and that be performed by 1). for and be used in patients who most from such as those with quality of life or on or not any diagnostic, or for HE in patients with for 1). this is encephalopathy and as its is not on clinical and is by outlined in the its and can have a on a can there may be an to such a patient impairment in quality of or cognitive Liver is under the treatment recommendations for treatment of the following: of or be 1). an for HE is 1). for of of is not in patients with cirrhosis with a high risk to HE with liver failure, is an for approach to management of HE is of care for patients with of be and of and their of HE treatment with of HE who are risk or to their need more and are in an care of encephalopathy are not in patients with cirrhosis. other of encephalopathy are the of encephalopathy may not be termed HE. In the clinical is treatment of both HE and in the management of is of of patients can be with of the to this is the of HE In to the other of the approach to treatment of HE, treatment is of the have not been by studies and are utilized based on These such as and such as such as and other have been In the a can be used to in patients who are to or have an is generally used as treatment for of data not as a for treatment of for it not the and these to be used of of a clinical search for and for the brain it is that the being a that the of in the and of have an beyond the studies have not those In most trials on have been in to the in of In is preferred to based on of In populations with a high of the use of has been the to that and were to was The use of further The of be when the three of the approach are with of every or are the is to to three This be It is a that lack of of of is by larger There is a for of to such as and severe and can has been used for the of HE in a number of it with other and in These trials of that was or to the with with for patients with has been in three trials to and one in cognitive improvement and with patients bouts to the of the of data the use of have been used for treatment of HE, data to their use are or most of these can be used their limited of trials that the manifestations of HE or There is no of on the of These through their as in have been used for treatment of of the for many are available and present as has been for HE, further clinical are was in a on patients who or more of HE in the 6 and who were on The of HE and as well as to clinical studies on the are under way and, may to clinical on patients with HE improvement by in and with is study of or no in patients with cirrhosis who from HE found of HE in the or to were not There was no in of in any of the of the shunting the that may be by the of by the This has its and was used in the for HE it is a As has for its and these for This is not It in improvement on or The may be of in to the may be in by when or when is not have the of and no have been on this on patients on or no on of HE, was to and for HE 1). is the for treatment of 1). is an to for of 1). can be used as an or to patients to can be used as an or to patients to is an for treatment of is an for treatment of There are no trials of for of from it is and of of HE in patients with as of HE to to is the to in patients who have one or more bouts of on treatment their of was to complications of its to the of HE, or HE, was with severe HE as a complication of a a it was to use HE treatment to HE. one study that HE any than selection has the of severe HE it can the original for may important with to the of low a of can to HE, as There is a lack of on to aim to by or The is associated with more bouts of It is used to HE as with other of HE, the that be by of bouts of HE in patients with liver to a search for of such as can be successfully with of HE in a of patients in a liver the risk for is for of of HE the 1). as an to is for of of HE the 1). or is not for the of HE 1). 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As a level in a patient of HE for of the used present has been for their to HE and other of brain The not be by or may changes to those with HE in of or are to are to for these have been for their use in HE, the results are brain be in every patient with and of brain to In rare cases, by may be a for HE, the be This with research the management of HE. such research be based on research the of HE. It is necessary to more which liver are for of which alterations in and failure of these liver which brain are to the of the and, which this that result in the emergence of HE or the research and clinical management in result in new and treatment that need and clinical There is a severe and unmet need for clinical trials on treatment on all the of HE. clinical studies are the number of patients and their utilization is There are no data on which and patients the and research is needed to the of there is an insufficient for resources and policies management of HE. that were for HE ago were a of care is study of treatment for HE be or the of care. It is to to and The of recently is in the of and there is a need for trials on HE. There is an unmet need for research that is necessary to a for clinical The of and has it is not to results among studies and the be It may be to and HE that the of liver failure and with more than one important area of is the term which was to I of is and This to be by a approach. the isolated liver failure and HE be by clinical and brain brain is and are needed to the of that can be in patients with liver be more classified and based on and to the of clinical practice and studies in They be on the of HE on and to use and the in clinical (Table on and among on aspects on and with treatment studies on that can which patients may from Development of to when and to the on (i.e., and use on on for and of dysfunction on who from the for to and on cognitive improvement on to and be the to new which have been and are not a for studies The existing literature from a lack of and this makes of data or to consistency the field have been published by is a of the