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Early Transplantation in Acute on Chronic Liver Failure: Who and When

  • Management of the Cirrhotic Patient (A Cardenas and P Tandon, Section Editors)
  • Published:
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Abstract

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).

Recent Findings

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.

Summary

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.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. •• 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.

    Article  Google Scholar 

  2. 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.

    Article  Google Scholar 

  3. • 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.

    Article  Google Scholar 

  4. 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.

    Article  Google Scholar 

  5. 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.

    Article  Google Scholar 

  6. 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.

    Article  Google Scholar 

  7. 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.

  8. 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.

  9. 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.

    Article  Google Scholar 

  10. 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.

    Article  Google Scholar 

  11. 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.

    Article  CAS  Google Scholar 

  12. 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.

    Article  Google Scholar 

  13. 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.

    Article  Google Scholar 

  14. 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.

    Article  Google Scholar 

  15. 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.

    Article  Google Scholar 

  16. 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.

    Article  Google Scholar 

  17. 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.

    Article  Google Scholar 

  18. •• 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.

    Article  Google Scholar 

  19. 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.

    Article  Google Scholar 

  20. •• 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.

  21. 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.

    Article  Google Scholar 

  22. 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.

    Article  Google Scholar 

  23. 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.

    Article  CAS  Google Scholar 

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Correspondence to Nadim Mahmud.

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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).

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Mahmud, N., Hernaez, R., Wu, T. et al. Early Transplantation in Acute on Chronic Liver Failure: Who and When. Curr Hepatology Rep 19, 168–173 (2020). https://doi.org/10.1007/s11901-020-00519-9

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  • DOI: https://doi.org/10.1007/s11901-020-00519-9

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