Review
Medicine, General & Internal
Carmine Gambino, Salvatore Piano, Paolo Angeli
Summary: ACLF is a syndrome that develops in patients with acutely decompensated chronic liver disease, characterized by high mortality, organ failures, and systemic inflammation. Different scientific societies have proposed diagnostic criteria and clinical characteristics for ACLF, along with established and experimental treatments. Further research is needed to better understand the pathophysiology of the syndrome and explore new therapies.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Gastroenterology & Hepatology
William Bernal, Constantine Karvellas, Faouzi Saliba, Fuat H. Saner, Philippe Meersseman
Summary: Acute-on-chronic liver failure syndrome involves liver function deterioration, extrahepatic organ failure, and high mortality rate, requiring rapid and coherent management in the intensive care unit to improve patient outcomes.
JOURNAL OF HEPATOLOGY
(2021)
Article
Gastroenterology & Hepatology
Francois Durand, Olivier Roux, Emmanuel Weiss, Claire Francoz
Summary: Acute-on-chronic liver failure (ACLF) is a disease characterized by rapid organ failure in patients with cirrhosis, with high mortality rates. The severity of ACLF can be classified into three grades, with grade 3 showing over 70% mortality within 28 days. While infections and bleeding are common causes, around 60% of ACLF cases have unidentified precipitating factors. Identifying high-risk cirrhosis patients and managing them carefully are crucial in preventing ACLF.
LIVER INTERNATIONAL
(2021)
Review
Gastroenterology & Hepatology
Maria Pilar Ballester, Ahmed Elshabrawi, Rajiv Jalan
Summary: Acute-on-chronic liver failure (ACLF) is a life-threatening condition characterized by acute decompensation, organ failure, and high mortality risk. Extracorporeal liver support systems have been developed to improve outcomes, but their impact on survival remains unclear. DIALIVE, a novel liver support device, shows promise in reducing ACLF progression and is associated with faster recovery compared to standard treatment. Liver transplantation is a lifesaving option for severe ACLF patients, but careful patient selection is essential for optimal outcomes. This review discusses the current perspectives on extracorporeal liver support and liver transplantation for ACLF patients.
LIVER INTERNATIONAL
(2023)
Review
Gastroenterology & Hepatology
Florent Artru, David Goldberg, Patrick S. Kamath
Summary: The authors debate whether patients with acute-on-chronic liver failure grade 3 (ACLF-3) should have higher liver transplant priority. They present a clinical case of a 62-year-old male with decompensated alcohol-associated cirrhosis and multiple comorbidities. The patient is at an exceedingly high risk of death without liver transplantation based on the severity of his liver disease and multiorgan failure.
JOURNAL OF HEPATOLOGY
(2023)
Article
Multidisciplinary Sciences
Peng Li, Xi Liang, Shan Xu, Ye Xiong, Jianrong Huang
Summary: This study aimed to evaluate the impact of artificial liver support system (ALSS) treatment before liver transplantation (LT), and assess the predictive values of current ACLF prognostic models for short-term prognosis after LT. The results showed that ALSS treatment combined with LT improved short-term survival rates in patients with HBV-related ACLF, and ALSS treatment pre-LT was identified as an independent protective factor affecting the 4-week survival rate after LT.
SCIENTIFIC REPORTS
(2021)
Review
Gastroenterology & Hepatology
Constantine J. J. Karvellas, Thierry Gustot, Javier Fernandez
Summary: Acute on chronic liver failure (ACLF) is the development of organ failure(s) in cirrhosis patients and has a high short-term mortality rate. Medical management of ACLF needs to consider the relationship between the underlying chronic liver disease/cirrhosis, precipitating insult, and involved organ systems. Intensive care management of ACLF focuses on promptly recognizing and treating triggering events and providing aggressive support for failing organs to ensure successful liver transplantation or recovery. The complexity of managing ACLF patients arises from their propensity to develop new organ failures and complications like infections or bleeding. A multidisciplinary team with expertise in critical care and transplant medicine is best suited for the management of critically ill ACLF patients. This review aims to identify common complications of ACLF and describe the appropriate management for critically ill patients awaiting liver transplantation, including organ support, prognostic assessment, and determining the likelihood of recovery.
LIVER INTERNATIONAL
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Antoine Wackenthaler, Sebastien Moliere, Thierry Artzner, Baptiste Michard, Maleka Schenck, Pietro Addeo, Camille Besch, Philippe Bachellier, Francis Schneider, Francis Veillon, Francois Faitot
Summary: Pre-operative imaging, specifically contrast-enhanced abdominal CT, was found to be significantly valuable in predicting post-transplantation survival in critically ill cirrhotic patients with severe ACLF. Three independent CT-derived prognostic factors - splenomegaly, liver atrophy, and vena cava diameter ratio - were identified and used to build a simple prognostic score, which was found to be an independent predictive factor in association with the Transplantation for ACLF3 Model (TAM) score, for predicting 1-year survival after liver transplantation.
EUROPEAN RADIOLOGY
(2022)
Review
Medicine, General & Internal
Arshi Khanam, Shyam Kottilil
Summary: ACLF is a complex disease that can occur in patients with or without liver cirrhosis, with pathophysiological mechanisms involving systemic inflammation and acute hepatic insult. Currently, no specific and definitive treatment is available apart from liver transplantation. Regenerative medicine using MSCs shows potential as an alternative treatment for ACLF.
FRONTIERS IN MEDICINE
(2021)
Review
Medicine, General & Internal
Xue Li, Liang Zhang, Chunmei Pu, Shanhong Tang
Summary: Acute-on-Chronic liver failure (ACLF) is a clinical syndrome with high short-term mortality. Alcoholic ACLF is more prevalent in Europe and America, while hepatitis B virus (HBV)-related ACLF is more common in the Asia-Pacific region. Liver transplantation (LT) is currently the most effective treatment, but the shortage of liver sources limits its clinical application. This study reviews the literature on LT in the treatment of ACLF and discusses the challenges, timing, and patient selection for LT in ACLF.
FRONTIERS IN MEDICINE
(2022)
Article
Gastroenterology & Hepatology
European Assoc Study Liver, Richard Moreau, Marta Tonon, Aleksander Krag, Paolo Angeli, Marina Berenguer, Annalisa Berzigotti, Javier Fernandez, Claire Francoz, Thierry Gustot, Rajiv Jalan, Maria Papp, Jonel Trebicka
Summary: Acute-on-chronic liver failure (ACLF) is a severe form of acutely decompensated cirrhosis characterized by organ system failure(s) and high short-term mortality. Patients with ACLF may benefit from liver transplantation and should be promptly stabilized for transplantation by treating identified precipitants and providing intensive care support. These guidelines aim to help clinicians recognize ACLF, make triage decisions, manage acute precipitants, support organ systems, determine futility of intensive care, and identify potential indications for liver transplantation.
JOURNAL OF HEPATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Cristina Maria Marginean, Denisa Pirscoveanu, Mihaela Popescu, Corina Maria Vasile, Anca Oana Docea, Radu Mitrut, Iulia Cristina Marginean, George Alexandru Iacob, Dan Mihai Firu, Paul Mitrut
Summary: Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute and severe decompensation of chronic liver disease (CLD) correlated with poor prognosis and increased mortality. Bacterial translocation and systemic inflammation are believed to be the determining factors in cases where the trigger is not recognized, while sepsis, alcohol consumption, and reactivation of chronic viral hepatitis are the common triggers. ACLF management involves preventing precipitating factors, supporting vital functions, managing complications, estimating prognosis, and considering liver transplantation.
Review
Gastroenterology & Hepatology
Peng Li, Xi Liang, Jinjin Luo, Jun Li
Summary: Acute-on-chronic liver failure (ACLF) is a critical clinical entity characterized by acute decompensation, organ failure, and high mortality in patients with chronic liver disease. The pathophysiology of ACLF involves systemic inflammation, immune-metabolism disorder, mitochondrial dysfunction, and microenvironment imbalance. Omics-based analytical techniques offer novel insights into the mechanisms of ACLF and can identify potential biomarkers and therapeutic targets. This paper reviews the current knowledge and recent advances in ACLF definitions, criteria, prognostic assessments, and the application of omics-based analyses in understanding ACLF biology.
LIVER INTERNATIONAL
(2023)
Review
Critical Care Medicine
Giovanni Perricone, Thierry Artzner, Eleonora De Martin, Rajiv Jalan, Julia Wendon, Marco Carbone
Summary: Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by acute deterioration of liver function and extrahepatic organ failures with high short-term mortality. ACLF has become a major cause of death in patients with cirrhosis and chronic liver disease. Systemic inflammation plays a key role in the pathophysiology of ACLF, which has led to the development of novel therapies currently being tested in clinical trials.
INTENSIVE CARE MEDICINE
(2023)
Review
Health Care Sciences & Services
Markus Kimmann, Jonel Trebicka
Summary: Acute-on-chronic liver failure (ACLF) is a severe complication in liver cirrhosis patients with high mortality. Identifying and treating the triggers of decompensation and ACLF, managing organ failures, and considering liver transplantation (LT) are crucial. However, there is no specific treatment for ACLF, and LT is often limited by contraindications. Bridging strategies and new therapeutic approaches are being explored. This review focuses on current management and potential future treatment options for ACLF.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Gastroenterology & Hepatology
Vinay Sundaram, Christina C. Lindenmeyer, Kirti Shetty, Robert S. Rahimi, Atef Al-Attar, Gianina Flocco, Brett E. Fortune, Cynthia Gong, Suryanarayana Challa, Haripriya Maddur, Janice H. Jou, Michael Kriss, Lance L. Stein, Alex H. Xiao, Ross H. Vyhmeister, Ellen W. Green, Braidie Campbell, Andrew J. Piscitello, William Cranford, Josh Levitsky, Constantine J. Karvellas
Summary: This retrospective study reviewed data from 10 centers in North America and found that patients with ACLF at liver transplantation have greater post-transplant healthcare resource utilization, including longer hospital stay, dialysis duration, discharge to a rehabilitation center, and higher 30-day readmission rates. Patients with ACLF-1, ACLF-2, and ACLF-3 had significantly longer hospital stay compared to those without ACLF. ACLF-3 was also associated with longer dialysis duration after transplantation and higher likelihood of discharge to a rehabilitation center. Bacterial infection after transplantation predicted longer hospital stay and higher 30-day readmission rates.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Review
Gastroenterology & Hepatology
Anjana A. Pillai, Michael Kriss, David P. Al-Adra, Ryan M. Chadha, Melissa M. Cushing, Khashayar Farsad, Brett E. Fortune, Aaron S. Hess, Robert Lewandowski, Mitra K. Nadim, Trevor Nydam, Pratima Sharma, Constantine J. Karvellas, Nicolas Intagliata
Summary: This article focuses on the hemostatic management of liver transplantation (LT) patients, including the unique aspects of the three main phases of care (before LT, perioperative, and after LT), and identifies critical areas of future research and knowledge gaps.
LIVER TRANSPLANTATION
(2022)
Article
Medicine, Research & Experimental
Dawn Opgenorth, Nadia Baig, Kirsten Fiest, Constantine Karvellas, Jim Kutsogiannis, Vincent Lau, Erika Macintyre, Janek Senaratne, Jocelyn Slemko, Wendy Sligl, Xiaoming Wang, Sean M. Bagshaw, Oleksa G. Rewa
Summary: The LIBERATE study aims to evaluate the effect of oral midodrine on ICU length of stay and duration of IV vasopressor support in critically ill patients, as well as other outcome measures related to IV vasopressor therapy.
Editorial Material
Anesthesiology
Dmitri Bezinover, Gianni Biancofiore, Marco Falcone, Costantine Karvellas, Shaid Husain, Fuat H. Saner
Summary: Solid organ transplantation is the best therapeutic option for patients with end-stage organ disease. However, infections remain a serious complication, with an increasing incidence of episodes due to antibiotic-resistant bacteria and opportunistic agents.
MINERVA ANESTESIOLOGICA
(2022)
Review
Critical Care Medicine
Jody C. Olson, Ram Subramanian, Constantine J. Karvellas
Summary: Liver transplantation is the only definitive treatment for advanced liver disease and liver failure. The number of liver transplantations is increasing globally due to the rising prevalence of liver disease. Intensive care providers need to possess knowledge of technical considerations, basic management, and common complications related to liver transplantation.
CURRENT OPINION IN CRITICAL CARE
(2022)
Article
Gastroenterology & Hepatology
Constantine J. Karvellas, Thomas M. Leventhal, Jorge L. Rakela, Jingwen Zhang, Valerie Durkalski, K. Rajender Reddy, Robert J. Fontana, R. Todd Stravitz, John R. Lake, William M. Lee, Justin R. Parekh
Summary: Liver transplantation is a life-saving treatment for acute liver failure patients. This study evaluated the long-term outcomes of patients listed for liver transplantation for acute liver failure. The 1- and 3-year post-transplant patient survival rates were 91% and 90%, respectively. Factors associated with death without transplantation included age, drug-induced liver injury, requirement for vasopressors, severe hepatic encephalopathy, and Model for End-Stage Liver Disease scores. Post-transplant outcomes for acute liver failure patients were excellent.
LIVER TRANSPLANTATION
(2023)
Article
Anesthesiology
Francois M. Carrier, Christian Vincelette, Helen Trottier, Eva Amzallag, Adrienne Carr, Prosanto Chaudhury, Khaled Dajani, Rene Fugere, Jeanne-Marie Giard, Nelson Gonzalez-Valencia, Alexandre Joosten, Stanislas Kandelman, Constantine Karvellas, Stuart A. McCluskey, Timur Ozelsel, Jeieung Park, Eve Simoneau, Michael Chasse
Summary: The objective of this study was to describe some components of perioperative care in liver transplantation as reported by clinicians. A cross-sectional clinical practice survey was conducted, and the results showed significant equipoise on the optimal perioperative management of this population.
CANADIAN JOURNAL OF ANESTHESIA-JOURNAL CANADIEN D ANESTHESIE
(2023)
Article
Critical Care Medicine
Rahul Nanchal, Ram Subramanian, Waleed Alhazzani, Joanna C. Dionne, William J. Peppard, Kai Singbartl, Jonathon Truwit, Ali H. Al-Khafaji, Alley J. Killian, Mustafa Alquraini, Khalil Alshammari, Fayez Alshamsi, Emilie Belley-Cote, Rodrigo Cartin-Ceba, Steven M. Hollenberg, Dragos M. Galusca, David T. Huang, Robert C. Hyzy, Mats Junek, Prem Kandiah, Gagan Kumar, Rebecca L. Morgan, Peter E. Morris, Jody C. Olson, Rita Sieracki, Randolph Steadman, Beth Taylor, Constantine J. Karvellas
Summary: To provide evidence-based recommendations for clinicians caring for adults with acute liver failure (ALF) or acute on chronic liver failure (ACLF) in the ICU, a multidisciplinary and international panel of experts developed guidelines. The panel followed strict procedures and policies, including systematic reviews and meta-analyses, to formulate recommendations based on the quality of evidence. The recommendations were categorized as strong or conditional, and some questions lacked sufficient evidence for a recommendation.
CRITICAL CARE MEDICINE
(2023)
Article
Critical Care Medicine
Rahul Nanchal, Ram Subramanian, Waleed Alhazzani, Joanna C. Dionne, William J. Peppard, Kai Singbartl, Jonathon Truwit, Ali H. Al-Khafaji, Alley J. Killian, Mustafa Alquraini, Khalil Alshammari, Fayez Alshamsi, Emilie Belley-Cote, Rodrigo Cartin-Ceba, Steven M. Hollenberg, Dragos M. Galusca, David T. Huang, Robert C. Hyzy, Mats Junek, Prem Kandiah, Gagan Kumar, Rebecca L. Morgan, Peter E. Morris, Jody C. Olson, Rita Sieracki, Randolph Steadman, Beth Taylor, Constantine J. Karvellas
CRITICAL CARE MEDICINE
(2023)
Review
Gastroenterology & Hepatology
R. Todd Stravitz, Robert J. Fontana, Constantine Karvellas, Valerie Durkalski, Brendan Mcguire, Jody A. Rule, Shannan Tujios, William M. Lee, Acute Liver Failure Study Grp
Summary: Acute liver failure (ALF) is a clinical syndrome characterized by rapid hepatocyte injury leading to liver failure without pre-existing cirrhosis. The Acute Liver Failure Study Group (ALFSG) was established in 1997 to study the causes, natural history, and management of ALF. Through clinical studies and collection of biosamples, significant findings have been made in the field. A recent conference was held to review ALFSG's accomplishments and discuss future research directions.
Article
Medicine, General & Internal
Babak J. Orandi, M. Chandler McLeod, Paul A. MacLennan, William M. Lee, Robert J. Fontana, Constantine J. Karvellas, Brendan M. McGuire, Cora E. Lewis, Norah M. Terrault, Jayme E. Locke
Summary: The FDA mandate limiting acetaminophen dosage to 325 mg/tablet in combination acetaminophen and opioid products was associated with a significant decrease in hospitalization rates and proportion of ALF cases involving acetaminophen and opioid toxicity.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2023)
Article
Gastroenterology & Hepatology
Ruben Hernaez, Constantine J. Karvellas, Yan Liu, Sophie-Caroline Sacleux, Saro Khemichian, Lance L. Stein, Kirti Shetty, Christina C. Lindenmeyer, Justin R. Boike, Douglas A. Simonetto, Robert S. Rahimi, Prasun K. Jalal, Manhal Izzy, Michael S. Kriss, Gene Y. Im, Ming V. Lin, Janice H. Jou, Brett E. Fortune, George Cholankeril, Alexander Kuo, Nadim Mahmud, Fasiha Kanwal, Faouzi Saliba, Vinay Sundaram, Thierry Artzner, Rajiv Jalan, Atef Al Attar, Kambiz Kosari, Richard Garcia, Gevork Salmastyan, William Cranford, Preet Patel, Pei Xue, Soumya Mishra, Madison Parks, Gianina Flocco, Mariana Hurtado, Islam Mohamed, Ross Vyhmeister, Christine R. Lopez, Braidie Campbell, Adam C. Winters, Mary Ann Simpson
Summary: The SALT-M score can predict one-year post-LT mortality in patients with severe ACLF. The ACLF-LT-LoS score can predict the median length of stay after LT. The use of these scores could assist in determining the benefits of transplantation.
JOURNAL OF HEPATOLOGY
(2023)
Article
Gastroenterology & Hepatology
Filipe S. Cardoso, Minjee Kim, Rui Pereira, Luis Bagulho, Pedro Fidalgo, Anna Pawlowski, Richard Wunderink, Nuno Germano, Sean M. Bagshaw, Juan G. Abraldes, Constantine J. Karvellas
Summary: This study aimed to describe and assess the impact of serum ammonia variation on the outcomes of critically ill patients with cirrhosis. It was found that higher serum ammonia levels in the early stage of ICU admission were associated with higher hospital mortality. Therefore, the variation in serum ammonia may have prognostic value.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Gastroenterology & Hepatology
Constantine J. J. Karvellas, Thierry Gustot, Javier Fernandez
Summary: Acute on chronic liver failure (ACLF) is the development of organ failure(s) in cirrhosis patients and has a high short-term mortality rate. Medical management of ACLF needs to consider the relationship between the underlying chronic liver disease/cirrhosis, precipitating insult, and involved organ systems. Intensive care management of ACLF focuses on promptly recognizing and treating triggering events and providing aggressive support for failing organs to ensure successful liver transplantation or recovery. The complexity of managing ACLF patients arises from their propensity to develop new organ failures and complications like infections or bleeding. A multidisciplinary team with expertise in critical care and transplant medicine is best suited for the management of critically ill ACLF patients. This review aims to identify common complications of ACLF and describe the appropriate management for critically ill patients awaiting liver transplantation, including organ support, prognostic assessment, and determining the likelihood of recovery.
LIVER INTERNATIONAL
(2023)
Article
Gastroenterology & Hepatology
Minjee Kim, Filipe S. Cardoso, Anna Pawlowski, Richard Wunderink, Daniela P. Ladner, Juan G. Abraldes, Constantine J. Karvellas
Summary: This observational cohort study examined the impact of MDR colonization and MDR infection on survival in critically ill cirrhosis patients. The results showed that MDR colonization and MDR infection were associated with lower transplant-free survival in these patients.
HEPATOLOGY COMMUNICATIONS
(2023)