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Acute-on-chronic liver failure (ACLF), which was described relatively recently (2013), is a severe form of acutely decompensated cirrhosis characterised by the existence of organ system failure(s) and a high risk of short-term mortality. ACLF is caused by an excessive systemic inflammatory response triggered by precipitants that are clinically apparent (e.g. , proven microbial infection with sepsis, severe alcohol-related hepatitis) or not. Since the description of ACLF, some important studies have suggested that patients with ACLF may benefit from liver transplantation and because of this, should be urgently stabilised for transplantation by receiving appropriate treatment of identified precipitants, and full general management, including support of organ systems in the intensive care unit (ICU). The objective of the present Clinical Practice Guidelines is to provide recommendations to help clinicians recognise ACLF, make triage decisions (ICU vs. no ICU), identify and manage acute precipitants, identify organ systems that require support or replacement, define potential criteria for futility of intensive care, and identify potential indications for liver transplantation. Based on an in-depth review of the relevant literature, we provide recommendations to navigate clinical dilemmas followed by supporting text. The recommendations are graded according to the Oxford Centre for Evidence-Based Medicine system and categorised as 'weak' or 'strong'. We aim to provide the best available evidence to aid the clinical decision-making process in the management of patients with ACLF. [ABSTRACT FROM AUTHOR]

Liver transplantation represents a life-saving treatment for patients with decompensated cirrhosis, a severe condition associated with a high risk of waiting list mortality. When decompensation occurs rapidly in the presence of extrahepatic organ failures, the condition is called acute-on-chronic liver failure, which is associated with an even higher risk of death, though liver transplantation can also markedly improve survival in affected patients. However, there are still gaps in our understanding of how to optimise prioritisation and organ allocation, as well as survival among patients with acute-on-chronic liver failure (both before and after transplant). Moreover, it is urgent to address inequalities in access to liver transplantation in patients with severe alcoholic hepatitis and non-alcoholic steatohepatitis. Several controversies still exist regarding gender and regional disparities, as well as the use of suboptimal donor grafts. In this review, we aim to provide a critical perspective on the role of liver transplantation in patients with decompensated cirrhosis and address areas of ongoing uncertainty. [ABSTRACT FROM AUTHOR]

Background and Aims Over the last decade, liver transplantation of sicker, older non-hepatitis C cirrhotics with multiple co-morbidities has increased in the United States. We sought to identify an easily applicable set of recipient factors among HCV negative adult transplant recipients associated with significant morbidity and mortality within five years after liver transplantation. Methods We collected national (n = 31,829, 2002–2015) and center-specific data. Coefficients of relevant recipient factors were converted to weighted points and scaled from 0–5. Recipient factors associated with graft failure included: ventilator support (five patients; hazard ratio [HR] 1.59; 95% CI 1.48–1.72); recipient age >60 years (three patients; HR 1.29; 95% CI 1.23–1.36); hemodialysis (three patients; HR 1.26; 95% CI 1.16–1.37); diabetes (two patients; HR 1.20; 95% CI 1.14–1.27); or serum creatinine ≥1.5 mg/dl without hemodialysis (two patients; HR 1.15; 95% CI 1.09–1.22). Results Graft survival within five years based on points (any combination) was 77.2% (0–4), 69.1% (5–8) and 57.9% (>8). In recipients with >8 points, graft survival was 42% (model for end-stage liver disease [MELD] score <25) and 50% (MELD score 25–35) in recipients receiving grafts from donors with a donor risk index >1.7. In center-specific data within the first year, subjects with ≥5 points ( vs. 0–4) had longer hospitalization (11 vs. 8 days, p  <0.01), higher admissions for rehabilitation (12.3% vs. 2.7%, p  <0.01), and higher incidence of cardiac disease (14.2% vs. 5.3%, p  <0.01) and stage 3 chronic kidney disease (78.6% vs. 39.5%, p  = 0.03) within five years. Conclusion The impact of co-morbidities in an MELD-based organ allocation system need to be reassessed. The proposed clinical tool may be helpful for center-specific assessment of risk of graft failure in non-HCV patients and for discussion regarding relevant morbidity in selected subsets. Lay summary Over the last decade, liver transplantation of sicker, older patient with multiple co-morbidities has increased. In this study, we show that a set of recipient factors (recipient age >60 years, ventilator status, diabetes, hemodialysis and creatinine >1.5 mg/dl) can help identify patients that may not do well after transplant. Transplanting sicker organs in patients with certain combinations of these characteristics leads to lower survival. [ABSTRACT FROM AUTHOR]

Summary: The case for using emergency liver transplantation in acute liver failure was made two decades ago by a series of single centre experiences. The development of models identifying a poor prognosis assisted the selection of patients for liver transplantation but none of these delivers both high sensitivity and specificity for prediction of death. Enhanced sensitivity favours the individual patient while enhanced specificity targets the pool of organs available at those who will derive greatest benefit. The non-transplant survival rates have improved considerably for certain cohorts of patients and these prognostic models have not been adjusted to reflect these changes. The presumption of transplant benefit can no longer be taken as established in paracetamol-related acute liver failure and a policy review is appropriate. In other scenarios, such as seronegative hepatitis and the phenotype of sub-acute liver failure, spontaneous survival rates remain low and the basis for liver transplantation remains sound. Outcomes after liver transplantation are improving but are not yet comparable to elective transplantation. The understanding of factors associated with failure after liver transplantation is improving but accurate definition of futility has not yet been attained. [ABSTRACT FROM AUTHOR]

The case for using emergency liver transplantation in acute liver failure was made two decades ago by a series of single centre experiences. The development of models identifying a poor prognosis assisted the selection of patients for liver transplantation but none of these delivers both high sensitivity and specificity for prediction of death. Enhanced sensitivity favours the individual patient while enhanced specificity targets the pool of organs available at those who will derive greatest benefit. The non-transplant survival rates have improved considerably for certain cohorts of patients and these prognostic models have not been adjusted to reflect these changes. The presumption of transplant benefit can no longer be taken as established in paracetamol-related acute liver failure and a policy review is appropriate. In other scenarios, such as seronegative hepatitis and the phenotype of sub-acute liver failure, spontaneous survival rates remain low and the basis for liver transplantation remains sound. Outcomes after liver transplantation are improving but are not yet comparable to elective transplantation. The understanding of factors associated with failure after liver transplantation is improving but accurate definition of futility has not yet been attained., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)