Acute-on-chronic liver failure: to admit to intensive care or not?

2020 ◽  
Vol 81 (9) ◽  
pp. 1-6
Author(s):  
Asif Arshad ◽  
Lylah Irshad ◽  
Theodore Nabavi ◽  
Tony Whitehouse
Keyword(s):  
Liver Failure ◽  
Organ Failure ◽  
Gastrointestinal Haemorrhage ◽  
Chronic Liver ◽  
Organ Support ◽  
Chronic Liver Failure ◽  
Short Term Mortality ◽  
Organ Failures ◽  
Clinical Scoring ◽  
Excessive Alcohol

Acute-on-chronic liver failure is used to describe an acute decline in liver function in a patient with existing liver disease combined with other organ failure. Acute-on-chronic liver failure is associated with high short-term mortality, and the greater the number and severity of organ failures, the higher the mortality. The most commonly identified precipitants of acute-on-chronic liver failure include bacterial infection, gastrointestinal haemorrhage, viral hepatitis and recent excessive alcohol intake. Since some of these aetiologies are treatable, organ failure may return to pre-decompensation levels in up to 55% of patients. As a result, a trial of critical care treatment may be appropriate for many of these patients. Clinical scoring tools may help clinicians recognise futility, allowing timely withdrawal of organ support and shifting the focus of care toward palliation.

scholarly journals Acute-on-chronic liver failure: definition, prognosis and management

2019 ◽  
Vol 11 (6) ◽  
pp. 458-467
Author(s):  
Ahmed Amin ◽  
Rajeshwar P Mookerjee
Keyword(s):  
Liver Transplantation ◽  
Liver Failure ◽  
Organ Failure ◽  
Limited Resource ◽  
Chronic Liver ◽  
Rapid Progression ◽  
Organ Shortage ◽  
Chronic Liver Failure ◽  
Hepatic Decompensation ◽  
Short Term Mortality

Acute-on-chronic liver failure (ACLF) is a recently described entity in chronic liver disease defined by acute hepatic decompensation, organ failure and a high risk of short-term mortality (usually less than 4 weeks). This condition is distinct from acute liver failure and stable progression of cirrhosis in numerous ways, including triggering precipitant factors, systemic inflammation, rapid progression and a potential for recovery. While a clear definition of ACLF has been forwarded from a large European Consortium study, some heterogeneity remains in how patients present and the types of organ failure, depending on whether they are described in Asian or European studies. Active alcoholism, acute alcoholic hepatitis and infections are the most frequent precipitants for ACLF. Underpinning the pathophysiology of ACLF is a state of persistent inflammation and immune dysfunction, collectively driving a systematic inflammatory response syndrome and an increased propensity to sepsis. Prevention and early treatment of organ failure are key in influencing survival. Given increasing organ shortage and more marginal grafts, liver transplantation is a limited resource and emphasises the need for new therapies to improve ACLF outcomes. Recent data indicate that liver transplantation has encouraging outcomes even in patients with advanced ACLF if patients are carefully selected during the permissive window of clinical presentation. ACLF remains a significant challenge in the field of hepatology, with considerable research and resource being channelled to improve upon the definition, prognostication, treatment and unravelling of mechanistic drivers. This Review discusses updates in ACLF definition, prognosis and management.

Leveraging omics to understand the molecular basis of acute-on-chronic liver failure

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Joan Clària
Keyword(s):  
Liver Failure ◽  
Organ Failure ◽  
Systemic Inflammation ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure ◽  
Short Term Mortality ◽  
Novel Biomarkers ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Abstract Acute-on-chronic liver failure (ACLF) is a complex syndrome that develops in patients with acutely decompensated cirrhosis. In this condition, dysbalanced immune function and excessive systemic inflammation are closely associated with organ failure and high short-term mortality. In this review, we describe how omic technologies have contributed to the characterization of the hyperinflammatory state in patients with acutely decompensated cirrhosis developing ACLF, with special emphasis on the role of metabolomics, lipidomics and transcriptomics in profiling the triggers (pathogen- and damage-associated molecular patterns [PAMPs and DAMPs]) and effector molecules (cytokines, chemokines, growth factors and bioactive lipid mediators) that lead to activation of the innate immune system. This review also describes how omic approaches can be invaluable tools to accelerate the identification of novel biomarkers that could guide the implementation of novel therapies/interventions aimed at protecting these patients from excessive systemic inflammation and organ failure.

scholarly journals Leukocytes, Systemic Inflammation and Immunopathology in Acute-on-Chronic Liver Failure

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2632
Author(s):  
Mireia Casulleras ◽  
Ingrid W. Zhang ◽  
Cristina López-Vicario ◽  
Joan Clària
Keyword(s):  
Liver Failure ◽  
Organ Failure ◽  
Chronic Liver ◽  
Decompensated Cirrhosis ◽  
Chronic Liver Failure ◽  
Drug Induced ◽  
Interleukin 22 ◽  
Secondary Infections ◽  
Short Term Mortality ◽  
Acute Decompensation

Acute-on-chronic liver failure (ACLF) is a complex syndrome that develops in patients with cirrhosis and is characterized by acute decompensation, organ failure(s) and high short-term mortality. ACLF frequently occurs in close temporal relationship to a precipitating event, such as acute alcoholic, drug-induced or viral hepatitis or bacterial infection and, in cases without precipitating events, probably related to intestinal translocation of bacterial products. Dysbalanced immune function is central to its pathogenesis and outcome with an initial excessive systemic inflammatory response that drives organ failure and mortality. This hyperinflammatory state ultimately impairs the host defensive mechanisms of immune cells, rendering ACLF patients immunocompromised and more vulnerable to secondary infections, and therefore to higher organ dysfunction and mortality. In this review, we describe the prevailing characteristics of the hyperinflammatory state in patients with acutely decompensated cirrhosis developing ACLF, with special emphasis on cells of the innate immune system (i.e., monocytes and neutrophils), their triggers (pathogen- and damage-associated molecular patterns [PAMPs and DAMPs]), their effector molecules (cytokines, chemokines, growth factors and bioactive lipid mediators) and the consequences on tissue immunopathology. In addition, this review includes a chapter discussing new emerging therapies based on the modulation of leukocyte function by the administration of pleiotropic proteins such as albumin, Toll-like receptor 4 antagonists, interleukin-22 or stem cell therapy. Finally, the importance of finding an appropriate intervention that reduces inflammation without inducing immunosuppression is highlighted as one of the main therapeutic challenges in cirrhosis.

Clinical Features of Hepatitis C Virus-Related Acute-On-Chronic Liver Failure in a Korean Population

2021 ◽  
Author(s):  
Jung Woo Choi ◽  
Jin-Kyu Cho ◽  
Sang Soo Lee ◽  
Jae Heon Kim ◽  
Hankyu Jeon ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatitis B Virus ◽  
Liver Failure ◽  
Chronic Liver ◽  
Chronic Liver Failure ◽  
Short Term ◽  
B Virus ◽  
Short Term Mortality ◽  
Very High

Abstract Background Acute-on-chronic liver failure (ACLF) is a widely recognized concept in which acute decompensation (AD) in patients with cirrhosis results in organ failures and high short-term mortality. However, few studies reflecting the various etiologies of cirrhosis are available. We aimed to investigate the clinical features of patients with hepatitis C virus (HCV)-related ACLF. Methods Between January 2005 and December 2018, 109 HCV-related cirrhosis patients who were hospitalized for AD (ascites, hepatic encephalopathy, gastrointestinal hemorrhage, and/or bacterial infection) were enrolled for ACLF defined by European Association for the Study of the Liver (EASL). Results ACLF developed in 35 patients (32.1%) on admission. Eight patients had ACLF grade 1, eight had ACLF grade 2, and 19 had ACLF grade 3. The 28-day and 90-day mortality rates were very low (2.7% and 5.4%, respectively) in patients without ACLF and very high (60.0% and 74.3%, respectively) in those with ACLF. In patients with HCV-related ACLF, the prevalence of liver failure was very low (17.1%), whereas that of kidney failure was very high (71.4%) compared to previous studies on hepatitis B virus-related ACLF and alcohol-related ACLF. Compared with all other prognostic scores, Chronic liver failure Consortium Organ Failure score most accurately predicted 90-day mortality, with an area under the receiver operator characteristic of 0.921. Conclusions HCV-related ACLF has unique clinical characteristics that are distinct from hepatitis B virus-related and alcohol-related ACLF. ACLF defined by EASL can be useful in predicting short-term mortality in HCV-related cirrhosis.

Inflammasome and extrahepatic organ failure in acute-on-chronic liver failure

2017 ◽  
Vol 1 ◽  
pp. 34-34
Author(s):  
Carmen Sendra ◽  
Javier Ampuero ◽  
Manuel Romero-Gómez
Keyword(s):  
Liver Failure ◽  
Organ Failure ◽  
Chronic Liver ◽  
Chronic Liver Failure

Liver failure

2020 ◽  
pp. 3089-3100
Author(s):  
Jane Macnaughtan ◽  
Rajiv Jalan
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Hepatic Encephalopathy ◽  
Liver Injury ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Organ Failure ◽  
Clinical Manifestations ◽  
Chronic Liver ◽  
Chronic Liver Failure

Liver failure occurs when loss of hepatic parenchymal function exceeds the capacity of hepatocytes to regenerate or repair liver injury. Acute liver failure is characterized by jaundice and prolongation of the prothrombin time in the context of recent acute liver injury, with hepatic encephalopathy occurring within 8 weeks of the first onset of liver disease. Acute-on-chronic liver failure is characterized by hepatic and/or extrahepatic organ failure in patients with cirrhosis associated with an identified or unidentified precipitating event. The commonest causes of acute liver failure are acute viral hepatitis and drugs. Acute-on-chronic liver failure is most commonly precipitated by infection, alcohol abuse, and superimposed viral infection. The main clinical manifestations are hepatic encephalopathy, coagulopathy, jaundice, renal dysfunction, and haemodynamic instability. Infection and systemic inflammation contribute to pathogenesis and critically contribute to prognosis. Specific therapy for the underlying liver disease is administered when available, but this is not possible for most causes of liver failure. Treatment is predominantly supportive, with particular emphasis on (1) correction or removal of precipitating factors; (2) if encephalopathy is present, using phosphate enemata, nonhydrolysed disaccharide laxatives, and/or rifaximin; (3) early detection and prompt treatment of complications such as hypoglycaemia, hypokalaemia, cerebral oedema, infection, and bleeding. The onset of organ failure should prompt discussion with a liver transplantation centre. The mortality of acute liver failure (without liver transplantation) is about 40%. Patients with acute liver failure who do not develop encephalopathy can be expected to recover completely. Those who recover from an episode of acute-on-chronic liver failure should be considered for liver transplantation because otherwise their subsequent mortality remains high.

Serum cholinesterase, an underestimated marker in the prediction of acute-on-chronic liver failure, organ failure and LTx-free survival in patients with liver cirrhosis?

2020 ◽  
Vol 73 ◽  
pp. S504
Author(s):  
Tammo Lambert Tergast ◽  
Abdul-Rahman Kabbani ◽  
Marie Schultalbers ◽  
Michael P. Manns ◽  
Markus Cornberg ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Liver Failure ◽  
Organ Failure ◽  
Chronic Liver ◽  
Serum Cholinesterase ◽  
Chronic Liver Failure ◽  
Free Survival
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