Purpose of Review
Acute on chronic liver failure (ACLF) is a unique syndrome that afflicts patients with chronic liver disease and results in high short-term mortality, > 50% at 28 days in patients with severe ACLF (grade 3, ACLF-3). Given this prognosis, there is an urgent need to understand risk factors for this condition, as well as selection criteria for patients who may benefit from liver transplantation (LT).
Several studies have identified risk factors for developing ACLF, including higher model for end-stage liver disease score, anemia, and morbid obesity, as well ACLF mortality, such as infection, increasing organ failures, and higher white blood cell count. Prognostic tools are now available as online calculators. Regarding LT in ACLF, data suggest that even patients with ACLF-3 may do well after LT, with 1-year survival > 80% in several studies. Improvement in organ failures prior to LT, higher donor quality, and lack of mechanical ventilation further improve outcomes. Importantly, ACLF-3 patients may have higher short-term wait list mortality than patients listed status-1a, suggesting that increased LT prioritization may be warranted.
ACLF is a high-mortality condition that frequently responds well to LT. Ongoing efforts to understand the natural history of ACLF and predictors of improved post-LT survival will facilitate LT criteria for this condition, which may ultimately include increased LT prioritization for selected patients.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
•• Sundaram V, Shah P, Wong RJ, Karvellas CJ, Fortune BE, Mahmud N, et al. Patients with acute on chronic liver failure grade 3 have greater 14-day waitlist mortality than status-1a patients. Hepatology. 2019;70(1):334–45. This study used national registry data to demonstrate that ACLF-3 patients wait listed for liver transplantation had increasing short-term mortality through 21 days which exceeded that of patients listed as status-1a.
Sarin SK, Kumar A, Almeida JA, Chawla YK, Fan ST, Garg H, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL). Hepatol Int. 2009;3(1):269–82.
• Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013;144(7):1426–37. e9. This is the seminal study that established the EASL-CLIF definition of ACLF.
Bajaj JS, O'Leary JG, Reddy KR, Wong F, Biggins SW, Patton H, et al. Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures. Hepatology. 2014;60(1):250–6.
Piano S, Tonon M, Vettore E, Stanco M, Pilutti C, Romano A, et al. Incidence, predictors and outcomes of acute-on-chronic liver failure in outpatients with cirrhosis. J Hepatol. 2017;67(6):1177–84.
Sundaram V, Jalan R, Ahn JC, Charlton MR, Goldberg DS, Karvellas CJ, et al. Class III obesity is a risk factor for the development of acute-on-chronic liver failure in patients with decompensated cirrhosis. J Hepatol. 2018;69(3):617–25.
Mahmud N, Hubbard RA, Kaplan DE, Taddei TH, Goldberg DS. Risk prediction scores for acute on chronic liver failure development and mortality. Liver International. 2020;40(5):1159-67.
Mahmud N, Sundaram V, Kaplan DE, Taddei TH, Goldberg DS. Grade 1 Acute on Chronic Liver Failure is a Predictor for Subsequent Grade 3 Failure. Hepatology. 2019;2. https://doi.org/10.1002/hep.31012.
Hernaez R, Kramer JR, Liu Y, Tansel A, Natarajan Y, Hussain KB, et al. Prevalence and short-term mortality of acute-on-chronic liver failure: a national cohort study from the USA. J Hepatol. 2019;70(4):639–47.
Jalan R, Stadlbauer V, Sen S, Cheshire L, Chang Y-M, Mookerjee RP. Role of predisposition, injury, response and organ failure in the prognosis of patients with acute-on-chronic liver failure: a prospective cohort study. Crit Care. 2012;16(6):R227.
O'Leary JG, Reddy KR, Garcia-Tsao G, Biggins SW, Wong F, Fallon MB, et al. NACSELD acute-on-chronic liver failure (NACSELD-ACLF) score predicts 30-day survival in hospitalized patients with cirrhosis. Hepatology. 2018;67(6):2367–74.
Gustot T, Fernandez J, Garcia E, Morando F, Caraceni P, Alessandria C, et al. Clinical course of acute-on-chronic liver failure syndrome and effects on prognosis. Hepatology. 2015;62(1):243–52.
Rice J, Dodge JL, Bambha KM, Bajaj JS, Reddy KR, Gralla J, et al. Neutrophil-to-lymphocyte ratio associates independently with mortality in hospitalized patients with cirrhosis. Clin Gastroenterol Hepatol. 2018;16(11):1786–91 e1.
Karvellas CJ, Garcia-Lopez E, Fernandez J, Saliba F, Sy E, Jalan R, et al. Dynamic prognostication in critically ill cirrhotic patients with multiorgan failure in ICUs in Europe and North America: a multicenter analysis. Crit Care Med. 2018;46(11):1783–91.
Jalan R, Saliba F, Pavesi M, Amoros A, Moreau R, Ginès P, et al. Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. J Hepatol. 2014;61(5):1038–47.
Artru F, Louvet A, Ruiz I, Levesque E, Labreuche J, Ursic-Bedoya J, et al. Liver transplantation in the most severely ill cirrhotic patients: a multicenter study in acute-on-chronic liver failure grade 3. J Hepatol. 2017;67(4):708–15.
Thuluvath PJ, Thuluvath AJ, Hanish S, Savva Y. Liver transplantation in patients with multiple organ failures: feasibility and outcomes. J Hepatol. 2018;69(5):1047–56.
•• Sundaram V, Jalan R, Wu T, Volk ML, Asrani SK, Klein AS, et al. Factors associated with survival of patients with severe acute-on-chronic liver failure before and after liver transplantation. Gastroenterology. 2019;156(5):1381–91. e3. This study identified several critical risk factors for improved post-transplant outcomes in patients with ACLF-3, including higher donor quality and lack of recipient mechanical ventilation.
Levesque E, Winter A, Noorah Z, Daurès JP, Landais P, Feray C, et al. Impact of acute-on-chronic liver failure on 90-day mortality following a first liver transplantation. Liver Int. 2017;37(5):684–93.
•• Sundaram V, Kogachi S, Wong RJ, Karvellas CJ, Fortune BE, Mahmud N, Levitsky J, Rahimi RS, Jalan R. Effect of the clinical course of acute-on-chronic liver failure prior to liver transplantation on post-transplant survival. Journal of Hepatology. 2020;1;72(3):481–8. This study demonstrated that patients with ACLF-3 at the time of wait listing who subsequently improved to ACLF 0–2 prior to transplantation had improved post-transplant survival relative to patients who remained at ACLF-3 prior to transplantation.
Ioannou GN. Transplant-related survival benefit should influence prioritization for liver transplantation especially in patients with hepatocellular carcinoma. Liver Transpl. 2017;23(5):652–62.
Sundaram V, Jalan R. Reply. Factors associated with survival of patients with severe acute-on-chronic liver failure before and after liver transplantation: unanswered questions. Gastroenterology. 2019;157(4):1163–4.
Huebener P, Sterneck M, Bangert K, Drolz A, Lohse A, Kluge S, et al. Stabilisation of acute-on-chronic liver failure patients before liver transplantation predicts post-transplant survival. Aliment Pharmacol Ther. 2018;47(11):1502–10.
Conflict of Interest
Dr. Sundaram serves on the speakers bureau for Abbvie, Gilead, Intercept, and Salix. Dr. Mahmud, Dr. Hernaez, and Dr. Wu have no disclosures to report.
Human and Animal Rights and Informed Consent
All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Management of the Cirrhotic Patient
About this article
Cite this article
Mahmud, N., Hernaez, R., Wu, T. et al. Early Transplantation in Acute on Chronic Liver Failure: Who and When. Curr Hepatology Rep (2020). https://doi.org/10.1007/s11901-020-00519-9
- End-stage liver disease
- Portal hypertension
- MELD score
- UNOS database