Elsevier

Journal of Hepatology

Volume 66, Issue 5, May 2017, Pages 1047-1081
Journal of Hepatology

Clinical Practice Guidelines
EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure

https://doi.org/10.1016/j.jhep.2016.12.003Get rights and content

Summary

The term acute liver failure (ALF) is frequently applied as a generic expression to describe patients presenting with or developing an acute episode of liver dysfunction. In the context of hepatological practice, however, ALF refers to a highly specific and rare syndrome, characterised by an acute abnormality of liver blood tests in an individual without underlying chronic liver disease. The disease process is associated with development of a coagulopathy of liver aetiology, and clinically apparent altered level of consciousness due to hepatic encephalopathy. Several important measures are immediately necessary when the patient presents for medical attention. These, as well as additional clinical procedures will be the subject of these clinical practice guidelines.

Introduction

The term acute liver failure (ALF) is frequently applied as a generic expression to describe patients presenting with or developing an acute episode of liver dysfunction. It is characterised by a deterioration in liver function tests, and potentially associated with dysfunction in other organs. ALF is frequently, but often incorrectly used to describe both acute deterioration in liver function in patients with chronic liver disease (a condition that should be termed acute-on-chronic liver failure [AoCLF]), or liver involvement in systemic disease processes. Liver injury secondary to alcohol, which presents as alcoholic hepatitis, and other forms of AoCLF, can be difficult to distinguish from ALF on occasion. However, there are clear differences, and different forms of management are required.

Following extensive liver resection, patients with or without underlying chronic liver disease, may develop a clinical syndrome of jaundice, coagulopathy and hepatic encephalopathy (HE). The presentation is very similar to that of a post-transplant “small for size syndrome” scenario. These syndromes are not considered within the scope of ALF, but do feature in some ALF databases, such as the European Liver Transplant Registry (ELTR). Extensive liver trauma is also included in ALF databases, but is not a cause of ALF unless there is loss of both venous and arterial inflows.

In the context of hepatological practice, ALF refers to a highly specific and rare syndrome, characterised by an acute abnormality of liver blood tests in an individual without underlying chronic liver disease. The disease process is associated with development of a coagulopathy of liver aetiology, as opposed to the coagulation disturbance seen in sepsis, and clinically apparent altered level of consciousness due to HE. The condition of patients who develop coagulopathy, but do not have any alteration to their level of consciousness is defined as acute liver injury (ALI). Thus, the term ALF is appropriately used to describe patients who develop both coagulopathy and altered mentation and will be the subject of these clinical practice guidelines.

The features of coagulopathy, increased serum transaminases, abnormal bilirubin and altered levels of consciousness may be seen in patients with a variety of systemic disease processes. Therefore, if there is no primary liver insult, these patients should be considered to have a secondary liver injury and not ALF; management should focus on the treatment of any underlying disease processes.

The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system [1]. The strength of recommendations reflects the quality of the underlying evidence. The GRADE system offers two grades of recommendation: strong (1) or weak (2) (Table 1). The CPGs thus consider the quality of evidence: the higher the quality of evidence, the more likely a strong recommendation is warranted; the greater the uncertainty, the more likely a weaker recommendation is warranted.

Section snippets

Definitions and main clinical features of ALF

The clinical course of ALF is initiated with a severe ALI. This is characterised by a two- to threetimes elevation of transaminases (as a marker of liver damage) associated with impaired liver function, i.e., jaundice and coagulopathy, in a patient without a chronic liver disease. This clinical description originated from observations of drug related hepatotoxicity, but is applicable to all presentations [2].

ALF was originally defined by Trey and Davidson in 1970 as fulminant liver failure,

Burden of ALF within Europe

The burden of ALF within the European Union (EU) remains unclear, with no collection of data regarding prevalence or incidence. Estimates are based on data presented in clinical series from referral and transplant units. Analysis of liver transplantation (LTx) data in the ELTR demonstrates that only 8% of all transplants are performed because of ALF as the primary indication. Sub-analysis of this 8% shows that 19% of cases are related to viral infection, 18% to drug-induced liver injury, 4%

Assessment and management at presentation

Several important measures are immediately necessary when the patient presents for medical attention (Table 4). Early discussion with a tertiary liver centre should be undertaken, even if the patient is not yet considered for transfer.

Cardiovascular management

Most patients presenting with ALF or severe ALI develop systemic vasodilation with reduced effective central blood volume. Early presentation with hyperlactataemia is probably a consequence of volume depletion, and responds to appropriate volume loading. Thereafter, ongoing hyperlactataemia is likely to reflect the severity of the underlying liver failure; the liver in unable to metabolise the increased lactate production seen in response to sympathetic drive and accelerated aerobic glycolysis (

Artificial and bioartificial liver devices

Liver assist devices have received much attention over recent years in the hope that they can provide an effective “bridge” to transplantation or recovery of liver function, mitigating the need for transplantation. Unfortunately, the dream of a mechanical “proxy liver” is a long way from being realised.

Preliminary artificial liver support devices were essentially filters designed to remove toxins through haemodialysis or adsorption using charcoal, and failed to show a survival benefit in ALF

Liver transplantation

The use of LTx has been the most significant development in the treatment of ALF in 40 years and has transformed survival [8], [15]. One year survival following emergency LTx is slightly worse than for routine transplants, but stands at an impressive 80%. The selection for LTx not only depends upon accurate prediction of survival without transplant, but also requires consideration of the survival potential after LTx, and whether a patient is too sick to transplant [317].

Paediatric acute liver failure

ALF in children is defined as a multisystem syndrome with the following components to the definition: hepatic-based coagulopathy defined as a PT >15 s or INR >1.5 not corrected by vitamin K in the presence of clinical HE, or a PT 20 s or INR 2.0 regardless of the presence or absence of HE. An essential component of the definition is the absence of a recognised underlying chronic liver disease. A difference of note is that HE is not considered to be an essential component of the definition of ALF

Conflict of interest

Dr. Bernardi, Dr. Simpson, Dr. Larsen, Dr. Wendon, Dr. Manns, and Dr. Dhawan have nothing to disclose.

Yaron Ilan is a consultant for Immuron, Teva, Enzo Biochem, Protalix, Therapix, Nasvax, Exalenz, Tiziana, and Natural Shield.

Dr. Escorsell report other from Vital Therapies, outside the submitted work.

Dr. Bernal reports personal fees from Ocera Therapeutics, personal fees from Vital Therapies, outside the submitted work.

Dr. Samuel reports other from Astellas, other from BMS, other from Gilead,

Acknowledgements

EASL would like to thank the reviewers for contributing their expertise to the production of these recommendations: Ali Canbay, François Durand and Ludwig Kramer.

The panel would like to also acknowledge the phenomenal contribution of William Bernal, who has contributed to this work and to the management of acute liver failure.

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    Juan Cordoba passed away during the preparation of this chapter.

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