AASLD position paper
These recommendations provide a data-supported approach. They are based on the following: (1) formal review and analysis of recently-published world literature on the topic [Medline search], (2) American College of Physicians Manual for Assessing Health Practices and Designing Practice Guidelines,1 (3) guideline policies, including the AASLD Policy on the Development and Use of Practice Guidelines and the AGA Policy Statement on Guidelines,2 (4) the experience of the authors in the specified topic. ALF, acute liver failure; NAC, N-acetylcysteine; HELLP, Hemolysis, Elevated Liver Enzymes, Low Platelets syndrome; ICH, intracranial hypertension; ICP, intracranial pressure; CT, computerized tomography; US ALFSG, United States Acute Liver Failure Study Group; CPP, cerebral perfusion pressure; MAP, mean arterial pressure; SIRS, systemic inflammatory response syndrome; FFP, fresh frozen plasma; rFVIIa, recombinant activated factor; GI, gastrointestinal; H2, histamine-2; PPI, proton pump inhibitors; CVVHD, continuous venovenous hemodialysis; APACHE, Acute Physiology and Chronic Health Evaluation; AFP, alpha fetoprotein; MELD, Model for End-stage Liver Disease. Intended for use by physicians, the recommendations in this document 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. This document has been designated as a Position Paper, since the topic contains more data based on expert opinion than on randomized controlled trials and thus is not considered to have the emphasis and certainty of a Practice Guideline. Nevertheless, it serves an important purpose of facilitating proper and high level patient care and we have characterized the quality of evidence supporting each recommendation, in accordance with the Practice Guidelines Committee of the AASLD recommendations used for full Practice Guidelines (Table 13). These recommendations are fully endorsed by the AASLD. Acute liver failure (ALF) is a rare condition in which rapid deterioration of liver function results in altered mentation and coagulopathy in previously normal individuals. U.S. estimates are placed at approximately 2,000 cases per year.4 The most prominent causes include drug-induced liver injury, viral hepatitis, autoimmune liver disease and shock or hypoperfusion; many cases (≈20%) have no discernible cause.5 Acute liver failure often affects young persons and carries a high morbidity and mortality. Prior to transplantation, most series suggested less than 15% survival. Currently, overall short-term survival with transplantation is greater than 65%.5 Because of its rarity, ALF has been difficult to study in depth and very few controlled therapy trials have been performed. As a result, standards of intensive care for this condition have not been established. The most widely accepted definition of ALF includes evidence of coagulation abnormality, usually an INR ≥1.5, and any degree of mental alteration (encephalopathy) in a patient without preexisting cirrhosis and with an illness of <26 weeks duration.6 Patients with Wilson disease, vertically-acquired HBV, or autoimmune hepatitis may be included in spite of the possibility of cirrhosis if their disease has only been recognized for <26 weeks. A number of other terms have been used including fulminant hepatic failure and fulminant hepatitis or necrosis. Acute liver failure is a better overall term that should encompass all durations up to 26 weeks. Terms used signifying length of illness such as hyperacute (<7 days), acute (7-21 days) and subacute (>21 days and <26 weeks) are not particularly helpful since they do not have prognostic significance distinct from the cause of the illness. For example, hyperacute cases may have a better prognosis but this is because most are due to acetaminophen toxicity.5 All patients with clinical or laboratory evidence of moderate to severe acute hepatitis should have immediate measurement of prothrombin and for in the prothrombin is by or more and is any evidence of altered the of ALF is and is the condition may with in to the intensive care is preferred the of ALF is should include review of to viral and or other severe is the may be by the or may be this is particularly include and of mental and a for of liver is often but not at is to the liver or to a of the liver be of liver due to liver may be in viral hepatitis or with or acute or of cirrhosis should be as such suggest liver disease, which may have the prognostic are not to patients with liver laboratory be in to the and of ALF (Table to coagulation should include as may be and arterial acetaminophen level and for other and viral hepatitis A and for Wilson disease, and and a in may be A liver most often the because of may be such as autoimmune hepatitis, liver disease, or hepatitis are As the important be to the patient to an to the patient to a and at a and to the patient on the for For patients in a the possibility of rapid of ALF with a Specific prognostic may the for For patients with ALF in an arterial of should immediate for to a and on a Patients with altered mentation should be to an for to a should in patients with or (Table because they may is important as the with patient may or or for transplantation should as as patients with for rapid deterioration it is to and are to the overall clinical transplantation is is important to the or other of of the prognosis and to include in the Patients with ALF should be and in an with a and to patients with ALF should be in the The of ALF should be to of ALF of the of and is suggested by evidence for as an intended or the use of of is a most to ALF severe liver as as are high may be are with acetaminophen and should of this evidence is Because acetaminophen is the cause of ALF in the United States and and is an acetaminophen should be in all patients with Low or acetaminophen do not acetaminophen since the of may be or may have been acetaminophen is or to have a few of activated may be for it is most if of it may be of as as to of activated in a to of not the of the for acetaminophen has been to be and for this purpose in controlled The acetaminophen may in the of liver but be used to due to or altered in the or of is in any of ALF in which acetaminophen is a or should be as as but may be of or more may be by or to followed by by and has few rare or patients with ALF may often be by or mental and may be is in is followed by may be with and for For patients with or acetaminophen of activated to in all patients the of acetaminophen level or or liver may be used in cases of acute liver failure in which acetaminophen is or of is may cause ALF, and the should include is no to the of but this should be in patients with a of severe which to a of are it may be to patients with and activated is very of survival have been without but more has been with care and and or are the accepted no controlled trials their 26 have not to be has been to of the in of to in patients with or has been to be more than has been used more in the United is not as a in the United it is widely in and the United it is as or These usually is no of such may and used for of has been in of or for an of to is often with other but has not been to be in have its use as a of overall ALF patients with or of and Patients with acute liver failure to should be for transplantation, as this is often the only A of have been with acute liver a should include of all the and the other than acetaminophen cause of the A that has been used for more than to is to cause liver and other have been to cause liver such should be included in a are no for are not a is of a as the cause of ALF is a of causes of ALF should be if a is or should be of include and (Table of and of all and and the of the of acute liver failure due to all but should be for of acute viral (Table is hepatitis has a cause of ALF hepatitis hepatitis A Acute hepatitis may be in a hepatitis hepatitis not to cause is a cause of liver failure in it is and to be more severe in This should be considered in with to an such as or acute viral hepatitis, as with many other of ALF, care is the used widely in the of hepatitis may be considered in patients with acute hepatitis have not been to a controlled in acute Acute liver failure due to of hepatitis may in the of or evidence that patients to be for are to such therapy should be with a and that such should be for of therapy to the AASLD Practice on of Chronic of causes patients or in the are at but of ALF have been in are in only of Liver is helpful in the should be with for or such as have been in hepatic hepatitis and acute liver failure be with care as no has been should be to and for of in patients with to of disease Patients with or or as the cause of acute liver failure should be with Wilson disease is an cause of ALF of cases in the US is because the fulminant of Wilson disease is considered to be without The disease in young by the of with to the of the is often with the are in of patients with ALF due to Wilson is but may be normal in up to 15% of cases and is often in other of high and as as hepatic measurement may the or are to suggest Wilson disease in the of other A high to is a of Wilson disease in this function is often as the cause to and to should include continuous or of with is not in ALF as is a of to this acute of the is more function is such should be is without Wilson disease is of the in which patients may have evidence of cirrhosis and be considered to have a of ALF rapid deterioration to the AASLD Practice on Wilson for more the and of patients with this for Wilson disease should include and for and hepatic liver is Patients in Wilson disease is the cause of acute liver failure be placed on the liver autoimmune hepatitis as with Wilson disease, patients may have preexisting disease and be considered as patients the most severe of the disease, and the of patients for therapy as by the AASLD Practice Guidelines for the and of ALF is not in that patients may be to may be a Liver may be helpful if include of severe hepatic by hepatitis, and of therapy may a therapeutic for patients at on the is autoimmune hepatitis is as the cause of acute liver liver should be considered to this Patients with acute liver failure due to autoimmune hepatitis should be with Patients should be placed on the for transplantation are A number of the of failure that has been and with or mortality. A of may be to the The of and may be with of such as and are by the The hepatic on hepatic rare rapid and of and are in is rapid and care is the only other transplantation has been in the to the of ALF due to which should be with on acute viral is important to in that ALF in may be by not to the For acute liver of or the with and are A often to as a of or in the of severe is not or may be with or with or may be but evidence of may be be and to of the of and may be The to failure or other causes of for and transplantation is ALF patients with evidence of is the of The hepatic as and are often The should be with hepatic the of liver transplantation may be as to As is of the causes of it is important to to transplantation of with hepatic failure is an for liver transplantation, is of the liver may cause hepatic may be should be by and and for the condition is is not an for such Acute severe hepatic with and patients with acute liver failure have a or and and liver to or the the of ALF be a may be helpful in autoimmune hepatitis, viral and Wilson of a that the may have been or the liver may be to to a that patients with ALF a they have clinical and the disease of acute and its of no or therapy that is to all patients with ALF has been are in this Because most patients with ALF to degree of that may have been of and other have in have not their in may systemic in patients with but this not in all has been to liver and function in patients with Use of in all of ALF be based on A controlled of for ALF is Because is no therapy for ALF in of intensive care for have been patients with evidence of acute liver but without coagulopathy or may be on a any patient with altered mental to an as the condition may be to and as as for and of of and and of are as and arterial should be and are to the of the in with and intracranial have been recognized as the most of may and is may to and injury, which may in in The to the of cerebral and in ALF are not is that are including in the and cerebral due to of as as may to the have been and used with to the of cerebral and the in patients with are by more evidence than no has been established. The of cerebral and in ALF is to of (Table is in patients with The of to to with to and to or more in patients A to is on the overall clinical patients with only may be on a with in a to in an is mental should be with to an if level of to an is with computerized is used to other causes of in mental such as intracranial is to be if may be with in is evidence that may a in the of cerebral has been to cause in have with an arterial level with cerebral on such evidence and on experience with of hepatic in patients with it has been suggested that with of or cerebral in A from the United States Acute Liver Failure Study patients to a of patients that therapy with a in survival but with no in of or in overall the use of in this is the for that in a transplantation As patients to or it is to the for of in this to is often used because it may cerebral its in this has not been in controlled of may be its in patients with hepatic Patients in of and of and as as and and for of intracranial should be Patients should be with at should be to patient that cause or in may it may be to use to which may be as a of the that to hepatic and ICH, should be controlled with Use of any is in of its on the of mental of should be used their by the may and may cause cerebral and thus to cerebral have use of as may be A randomized controlled of in ALF no in overall but a in cerebral at in the A clinical not on the of or may the of this but it be as a at this The use of in ALF is a of is used the United with not it and it A of the in the US used in of from a more review of more than used in a more than the use of of cerebral be The clinical of including and are not and other such as or of are only in the of the not evidence of at of as and measurement of and that are in of have thus not been in A purpose of is to in and in cerebral perfusion as mean arterial that be to The of such is to and survival of a or of is particularly important liver transplantation, in cause in cerebral is considered a to liver transplantation in many of ALF patients and and may this but is no of patients have the of transplantation are and of experience which provide helpful and may survival but are no controlled trials to an overall survival is the and in intracranial in based on data on patients at U.S. that a of with but the of with the use of or is not have the of of coagulation with of recombinant activated may use of results a in the of cases with the data not patients it may be to immediate the an is to are and should be if with from patients with cerebral that may if this level be of systemic may be to as on or by with is in the term in cerebral has been in controlled trials to of in ALF its use has been with of a of is to in The may be or as has not is a with use in patients with and may use of to or may from of is not to to is to cerebral but this is a series of patients with ALF, of of to be of of should be if cerebral is to cerebral and this study not on or A randomized controlled of continuous in ALF patients no in of cerebral and no survival of cerebral in the has been that cerebral with cerebral by cerebral on is no for in patients with is not controlled with and other may be in an to and this acute it be as A controlled of of to of in patients with ALF and severe that and of may be used to the in not be in this The of as a in or may be considered severe not to other has been to systemic their and may to mean arterial which are often used in the and of by and of the have been in a controlled to no in patients with ALF with to cerebral or may or in patients with has been in to of by or or by a experience has a of in patients with ALF as but has not been to a controlled of include of coagulation and of should be if may be but has been the patients to or the should be to and should be should be with and is no the and intracranial is considered for patients are for transplantation the of for of intracranial are to evidence of the of intracranial should be and may be considered in to the ICP, but use of is not helpful and not may be considered for intracranial should not be used to in patients with acute liver failure All patients with ALF are at for of or or which may transplantation or the therapy the of in of patients with ALF, but no survival has been it difficult to often for have not been to survival of mental in particularly in patients with acetaminophen may the of are not for and of and for and should be a for or are no controlled trials to the use of the of of of cerebral in have suggested an the systemic inflammatory response and to of that have been to the of that of are with of cerebral and that may it is that and may the of cerebral and This is to be should be to and as as and should be and may be considered but have not been to overall are in patients with ALF as previously patients at for of coagulation is of and may that are often the of it is not to with fresh frozen is an is and in the of coagulopathy INR to the with of use of the of coagulation as a of the of ALF patients and to which may is in a of of to be to the use of in patients or use of for evidence of severe are not used a is the of it is to use a of more of in patients with or in other of that are be of are usually considered Patients with approximately should be with no in the of a prothrombin of activated may be used in coagulopathy in patients with liver A of patients with ALF that of in with more of coagulopathy and thus be in facilitating of in patients particularly in the of in which is a This study and analysis of for is approximately it be therapy for prothrombin is only in the of or to is a recognized of A study that for more than and coagulopathy the only for in patients of all for in have included hepatic and shock and Patients with acute liver failure are thus at high for such as have been used in the of in their has been in has been to be in many and have been randomized trials and a which suggested that may be as in and be with of than which a to in patients that but not the of the of for the of proton pump as have their in trials no in patients on but study may have of have been to be and are as may provide but this to be may be as Patients with ALF in the should with or as a for with with failure in the are and of important and difficult in the of of function is in this many patients with ALF the patient with cirrhosis and may be on due to from altered mental of the and patients Low systemic results in in the and of a may in and with as is preferred than as all should to and of and may to or may be in to mean arterial of at has been which are used to in ALF and they are at such as and have been to the other has been with systemic of any the and with ALF to and they should be used if to perfusion of that are systemic is and should not be used in the of intracranial perfusion with normal systemic Acute failure is a in patients with and may be due to or acute The of failure may be greater with acetaminophen or other is few patients of failure it often to and may a should be to function by such as and and by the and of is continuous than of therapy continuous venovenous should be as they have been in randomized trials to in in and intracranial with of contrast are with in the of hepatic and should be used with contrast be with may be of this The of and in and function has evidence to be as of the of in ALF at this may have other as that or may be in patients with cirrhosis and has the of this patients with ALF as A study of in patients with ALF that in very the with cerebral and results that at this the with use to its in patients with The that as as to of the liver transplantation for ALF to a of as a of severe in This is based on and have been with patients for more than to be be to and of in patients with acute liver failure is for acute it is that a continuous than an be used should be considered in a patient to that has with such as or but not should be used if to of A number of are in and may and are by and the should be with continuous because may be in the of and are and may the is should be of should be per of is in most have not been to be to other are severe is an the of particularly with should be and may the of due to in be in patients with acute liver as as and should be with of liver transplantation the only therapy for patients are to of to As the of transplantation has with in overall survival from as as 15% in the to in care and more such as acetaminophen a better overall have survival are to 15% in the survival for ALF have been to be as high as to but data are not the U.S. only of patients a liver of the overall of patients for on the series have of for as high as the that ALF the condition for which the most is of liver or other to transplantation and better prognostic to overall survival for the liver transplantation may the of but its use has thus been very as a of for and in this hepatic transplantation is in acute liver failure prognostic suggest a high of A to the liver a but The for the liver and in all the many A of have been to with no evidence of only and no or other in a or placed in an may of and of coagulation the of hepatic may be but no in hepatic function or has been of or other have been used in in with or without controlled trials have been and suggest no to with or without short-term survival for a of patients with ALF with a but of results by be the of this be established. All such trials are difficult to and to due to the of the of of disease and to A all of no for liver for the of A of other have been including liver and be and their use to have been thus or have been it that the liver in but not all but this may weeks or to the to liver that that liver be for of liver are not of clinical their in the of acute liver failure of to transplantation, and of prognosis in ALF is a from data on of to the of that to this The College have been the most and most of the prognostic for have from to and from to such prognostic have to have but to based on of in patients with in acute viral hepatitis cases with a of and a of but in and have to be less than College in a prognostic in patients with ALF due to including College of and prothrombin and the Acute Physiology and Chronic Health and a of the The analysis that College and in a the College more than use of to many patients The authors that an of on a of to College with a better of but this only in such as and the length of of illness and of have previously been as important prognostic in not in the U.S. study of ALF to Patients in or less than patients in or to without a liver The most of in this study of ALF, as patients with ALF due to hepatitis shock or disease all other survival. prognostic have been including of of and liver of the and of have more is to their The Model for End-stage Liver widely used to patients with liver disease are for liver be as to ALF, a condition from prognostic do not and for liver is thus not of ALF as and for and of transplantation should be in all patients that evidence of Because patients may care in a with experience and in patients with ALF the for The authors the Practice Guidelines Committee of the AASLD for their in the of this The of the Practice Guidelines Committee include and The authors have no of to