Exploration of Digestive Diseases

From: Acute decompensation and acute-on-chronic liver failure

Table 3. Triggering factors in AD and ACLF

Triggering factors	AD	ACLF
Unknown	57%	10–50%
Known	Infections (58%)	Infections (48%)
	HBV reactivation	HBV reactivation
	HAV infection	HAV infection
	HEV infection	HEV infection
	Alcohol-related hepatitis	Alcohol-related hepatitis
	DILI	DILI
	Neurotoxic drugs	Neurotoxic drugs
	GI bleeding	GI bleeding^*
	Surgery	Native American ancestry
	Trauma
	TIPS
	TACE
	RFA
	Portal vein thrombosis

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^* Gastrointestinal (GI) bleeding is not accepting a trigger factor for ACLF in APASL unless it fulfills the APASL-ACLF criteria and causes jaundice and coagulopathy. AD: acute decompensation; ACLF: acute-on-chronic liver failure; DILI: drug-induced liver injury; RFA: radiofrequency ablation; TACE: transarterial chemoembolization; TIPS: transjugular intrahepatic portosystemic shunt

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Author contributions

SA: Conceptualization, Investigation, Writing—review & editing.

Conflicts of interest

The author declares no conflicts of interest.

Ethical approval

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Consent to participate

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References

European Association for the Study of the Liver. EASL Clinical Practice Guidelines on acute-on-chronic liver failure. J Hepatol. 2023;79:461–91. [DOI] [PubMed]

Ferstl P, Trebicka J. Acute Decompensation and Acute-on-Chronic Liver Failure. Clin Liver Dis. 2021;25:419–30. [DOI] [PubMed]

Trebicka J, Fernandez J, Papp M, Caraceni P, Laleman W, Gambino C, et al.; PREDICT STUDY group of the EASL-CLIF CONSORTIUM. PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis. J Hepatol. 2021;74:1097–108. [DOI] [PubMed]

Sarin SK, Choudhury A, Sharma MK, Maiwall R, Mahtab MA, Rahman S, et al.; APASL ACLF Research Consortium (AARC) for APASL ACLF working Party. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update. Hepatol Int. 2019;13:353–90. [DOI] [PubMed] [PMC]

Wang H, Tong J, Xu X, Chen J, Mu X, Zhai X, et al. Reversibility of acute-on-chronic liver failure syndrome in hepatitis B virus-infected patients with and without prior decompensation. J Viral Hepat. 2022;29:890–8. [DOI] [PubMed]

Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, et al.; CANONIC Study Investigators of the EASL–CLIF Consortium. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013;144:1426–37.e9. [DOI] [PubMed]

Zaccherini G. Clinical and pathophysiological characterization of patients with acutely decompensated cirrhosis and acute-on-chronic liver failure [dissertation]. Bologna: Universita di Bologna; 2022.

Br VK, Sarin SK. Acute-on-chronic liver failure: Terminology, mechanisms and management. Clin Mol Hepatol. 2023;29:670–89. [DOI] [PubMed] [PMC]

Hernaez R, Li H, Moreau R, Coenraad MJ. Definition, diagnosis and epidemiology of acute-on-chronic liver failure. Liver Int. 2023. [DOI] [PubMed]

10.

Bajaj JS, O’Leary JG, Lai JC, Wong F, Long MD, Wong RJ, et al. Acute-on-Chronic Liver Failure Clinical Guidelines. Am J Gastroenterol. 2022;117:225–52. [DOI] [PubMed]

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;67:2367–74. [DOI] [PubMed]

12.

Karvellas CJ, Bajaj JS, Kamath PS, Napolitano L, O’Leary JG, Solà E, et al. AASLD Practice Guidance on Acute-on-chronic liver failure and the management of critically ill patients with cirrhosis. Hepatology. 2024;79:1463–502. [DOI] [PubMed]

13.

Engelmann C, Berg T. Management of Infectious Complications Associated with Acute-on-Chronic Liver Failure. Visc Med. 2018;34:261–8. [DOI] [PubMed] [PMC]

14.

Leao GS, Lunardi FL, Picon RV, Tovo CV, de Mattos AA, de Mattos AZ. Acute-on-chronic liver failure: a comparison of three different diagnostic criteria. Ann Hepatol. 2019;18:373–8. [DOI] [PubMed]

15.

Torre A, Cisneros-Garza LE, Castillo-Barradas M, Navarro-Alvarez N, Sandoval-Salas R, González-Huezo MS, et al. Consensus document on acute-on-chronic liver failure (ACLF) established by the Mexican Association of Hepatology. Ann Hepatol. 2023;28:101140. [DOI] [PubMed]

16.

Angeli P, Ginès P, Wong F, Bernardi M, Boyer TD, Gerbes A, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. J Hepatol. 2015;62:968–74. [DOI] [PubMed]

17.

Arroyo V, Moreau R, Jalan R. Acute-on-Chronic Liver Failure. N Engl J Med. 2020;382:2137–45. [DOI] [PubMed]

18.

Clària J, Stauber RE, Coenraad MJ, Moreau R, Jalan R, Pavesi M, et al.; CANONIC Study Investigators of the EASL-CLIF Consortium and the European Foundation for the Study of Chronic Liver Failure (EF-CLIF). Systemic inflammation in decompensated cirrhosis: Characterization and role in acute-on-chronic liver failure. Hepatology. 2016;64:1249–64. [DOI] [PubMed]

19.

Yang P, Formanek P, Scaglione S, Afshar M. Risk factors and outcomes of acute respiratory distress syndrome in critically ill patients with cirrhosis. Hepatol Res. 2019;49:335–43. [DOI] [PubMed] [PMC]

20.

Premkumar M, Saxena P, Rangegowda D, Baweja S, Mirza R, Jain P, et al. Coagulation failure is associated with bleeding events and clinical outcome during systemic inflammatory response and sepsis in acute-on-chronic liver failure: An observational cohort study. Liver Int. 2019;39:694–704. [DOI] [PubMed]

21.

Jalan R, Saliba F, Pavesi M, Amoros A, Moreau R, Ginès P, et al.; CANONIC study investigators of the EASL-CLIF Consortium. Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. J Hepatol. 2014;61:1038–47. [DOI] [PubMed]

22.

Kumar R, Mehta G, Jalan R. Acute-on-chronic liver failure. Clin Med (Lond). 2020;20:501–4. [DOI] [PubMed] [PMC]

23.

Lin SH, Chen WT, Tsai MH, Liu LT, Kuo WL, Lin YT, et al. A novel prognostic model to predict mortality in patients with acute-chronic liver failure in intensive care unit. Intern Emerg Med. 2024;19:721–30. [DOI] [PubMed]

24.

Li H, Chen L, Zhang N, Li S, Zeng B, Pavesi M, et al. Characteristics, Diagnosis and Prognosis of Acute-on-Chronic Liver Failure in Cirrhosis Associated to Hepatitis B. Sci Rep. 2016;6:25487. [DOI] [PubMed] [PMC]

25.

Choudhury A, Kumar M, Sharma BC, Maiwall R, Pamecha V, Moreau R, et al.; APASL ACLF working party. Systemic inflammatory response syndrome in acute-on-chronic liver failure: Relevance of ‘golden window’: A prospective study. J Gastroenterol Hepatol. 2017;32:1989–97. [DOI] [PubMed]

26.

Abbas N, Rajoriya N, Elsharkawy AM, Chauhan A. Acute-on-chronic liver failure (ACLF) in 2022: have novel treatment paradigms already arrived? Expert Rev Gastroenterol Hepatol. 2022;16:639–52. [DOI] [PubMed]

27.

Hoshi H, Chu P, Yoshida A, Taniki N, Morikawa R, Yamataka K, et al. Vulnerability to recurrent episodes of acute decompensation/acute-on-chronic liver failure characterizes those triggered by indeterminate precipitants in patients with liver cirrhosis. PLoS One. 2021;16:e0250062. [DOI] [PubMed] [PMC]

28.

Wong F, Piano S, Singh V, Bartoletti M, Maiwall R, Alessandria C, et al.; International Club of Ascites Global Study Group. Clinical features and evolution of bacterial infection-related acute-on-chronic liver failure. J Hepatol. 2021;74:330–9. [DOI] [PubMed]

29.

Li H, Wieser A, Zhang J, Liss I, Markwardt D, Hornung R, et al. Patients with cirrhosis and SBP: Increase in multidrug-resistant organisms and complications. Eur J Clin Invest. 2020;50:e13198. [DOI] [PubMed]

30.

Su H, Tong J, Liu X, Li C, Chen J, Xu X, et al. Characteristics and outcome of nosocomial bloodstream infection in patients with acute-on-chronic liver failure. Eur J Gastroenterol Hepatol. 2021;33:83–8. [DOI] [PubMed]

31.

Bajaj JS, Reddy RK, Tandon P, Wong F, Kamath PS, Biggins SW, et al. Prediction of Fungal Infection Development and Their Impact on Survival Using the NACSELD Cohort. Am J Gastroenterol. 2018;113:556–63. [DOI] [PubMed]

32.

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;69:617–25. [DOI] [PubMed]

33.

Fernández J, Acevedo J, Wiest R, Gustot T, Amoros A, Deulofeu C, et al.; European Foundation for the Study of Chronic Liver Failure. Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis. Gut. 2018;67:1870–80. [DOI] [PubMed]

34.

Wang T, Tan W, Wang X, Zheng X, Huang Y, Li B, et al.; Chinese (Acute on) Chronic Liver Failure Consortium (Ch-CLIF.C). Role of precipitants in transition of acute decompensation to acute-on-chronic liver failure in patients with HBV-related cirrhosis. JHEP Rep. 2022;4:100529. [DOI] [PubMed] [PMC]

35.

Tang X, Qi T, Li B, Chen J. Pre-acute-on-chronic liver failure in hepatitis B-related patients. J Hepatol. 2021;74:479–80. [DOI] [PubMed]

36.

Farias AQ, Vilalta AC, Zitelli PM, Pereira G, Goncalves LL, Torre A, et al.; ACLARA Study Collaborators. Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America. Gastroenterology. 2023;165:696–716. [DOI] [PubMed]

37.

Engelmann C, Zhang IW, Clària J. Mechanisms of immunity in acutely decompensated cirrhosis and acute-on-chronic liver failure. Liver Int. 2023. [DOI] [PubMed]

38.

Schierwagen R, Gu W, Brieger A, Brüne B, Ciesek S, Đikić I, et al. Pathogenetic mechanisms and therapeutic approaches of acute-to-chronic liver failure. Am J Physiol Cell Physiol. 2023;325:C129–40. [DOI] [PubMed]

39.

Gawrieh S, Dasarathy S, Tu W, Kamath PS, Chalasani NP, McClain CJ, et al.; AlcHepNet Investigators. Randomized trial of anakinra plus zinc vs. prednisone for severe alcohol-associated hepatitis. J Hepatol. 2024;80:684–93. [DOI] [PubMed]

40.

Weiss E, Grange Pdl, Defaye M, Lozano JJ, Aguilar F, Hegde P, et al. Characterization of Blood Immune Cells in Patients With Decompensated Cirrhosis Including ACLF. Front Immunol. 2021;11:619039. [DOI] [PubMed] [PMC]

41.

Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, et al. Time to Treatment and Mortality during Mandated Emergency Care for Sepsis. N Engl J Med. 2017;376:2235–44. [DOI] [PubMed] [PMC]

42.

Li B, Gao Y, Wang X, Qian Z, Meng Z, Huang Y, et al. Clinical features and outcomes of bacterascites in cirrhotic patients: A retrospective, multicentre study. Liver Int. 2020;40:1447–56. [DOI] [PubMed]

43.

Gonwa TA, Wadei HM. The challenges of providing renal replacement therapy in decompensated liver cirrhosis. Blood Purif. 2012;33:144–8. [DOI] [PubMed]

44.

Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60:715–35. [DOI] [PubMed]

45.

Acharya C, Bajaj JS. Current Management of Hepatic Encephalopathy. Am J Gastroenterol. 2018;113:1600–12. [DOI] [PubMed]

46.

Devlin JW, Skrobik Y, Gélinas C, Needham DM, Slooter AJC, Pandharipande PP, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46:e825–73. [DOI] [PubMed]

47.

Fernández J, Clària J, Amorós A, Aguilar F, Castro M, Casulleras M, et al. Effects of Albumin Treatment on Systemic and Portal Hemodynamics and Systemic Inflammation in Patients With Decompensated Cirrhosis. Gastroenterology. 2019;157:149–62. [DOI] [PubMed]

48.

Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021;49:e1063–143. [DOI] [PubMed]

49.

Avni T, Lador A, Lev S, Leibovici L, Paul M, Grossman A. Vasopressors for the Treatment of Septic Shock: Systematic Review and Meta-Analysis. PLoS One. 2015;10:e0129305. [DOI] [PubMed] [PMC]

50.

Kim G, Huh JH, Lee KJ, Kim MY, Shim KY, Baik SK. Relative Adrenal Insufficiency in Patients with Cirrhosis: A Systematic Review and Meta-Analysis. Dig Dis Sci. 2017;62:1067–79. [DOI] [PubMed]

51.

Arabi YM, Aljumah A, Dabbagh O, Tamim HM, Rishu AH, Al-Abdulkareem A, et al. Low-dose hydrocortisone in patients with cirrhosis and septic shock: a randomized controlled trial. CMAJ. 2010;182:1971–7. [DOI] [PubMed] [PMC]

52.

Fernández J, Escorsell A, Zabalza M, Felipe V, Navasa M, Mas A, et al. Adrenal insufficiency in patients with cirrhosis and septic shock: Effect of treatment with hydrocortisone on survival. Hepatology. 2006;44:1288–95. [DOI] [PubMed]

53.

Jentzer JC, Mathier MA. Pulmonary Hypertension in the Intensive Care Unit. J Intensive Care Med. 2016;31:369–85. [DOI] [PubMed]

54.

Krowka MJ, Fallon MB, Kawut SM, Fuhrmann V, Heimbach JK, Ramsay MAE, et al. International Liver Transplant Society Practice Guidelines: Diagnosis and Management of Hepatopulmonary Syndrome and Portopulmonary Hypertension. Transplantation. 2016;100:1440–52. [DOI] [PubMed]

55.

Abdallah MA, Waleed M, Bell MG, Nelson M, Wong R, Sundaram V, et al. Systematic review with meta-analysis: liver transplant provides survival benefit in patients with acute on chronic liver failure. Aliment Pharmacol Ther. 2020;52:222–32. [DOI] [PubMed]

56.

Mathurin P, Moreno C, Samuel D, Dumortier J, Salleron J, Durand F, et al. Early liver transplantation for severe alcoholic hepatitis. N Engl J Med. 2011;365:1790–800. [DOI] [PubMed]

57.

Bajaj JS, O'Leary JG, Tandon P, Wong F, Kamath PS, Biggins SW, et al. Targets to improve quality of care for patients with hepatic encephalopathy: data from a multi-centre cohort. Aliment Pharmacol Ther. 2019;49:1518–27. [DOI] [PubMed] [PMC]

58.

Karvellas CJ, Garcia-Lopez E, Fernandez J, Saliba F, Sy E, Jalan R, et al.; Chronic Liver Failure Consortium and European Foundation for the Study of Chronic Liver Failure. Dynamic Prognostication in Critically Ill Cirrhotic Patients With Multiorgan Failure in ICUs in Europe and North America: A Multicenter Analysis. Crit Care Med. 2018;46:1783–91. [DOI] [PubMed]

59.

Gustot T, Fernandez J, Garcia E, Morando F, Caraceni P, Alessandria C, et al.; CANONIC Study Investigators of the EASL-CLIF Consortium. Clinical Course of acute-on-chronic liver failure syndrome and effects on prognosis. Hepatology. 2015;62:243–52. [DOI] [PubMed]

60.

Kumar V, Choudhury AK, Maiwall R, Al Mahtab M, Rahman S, Alam MS, et al. Degree of hemodynamic derangements correlate with poor outcomes in acute on chronic liver failure (ACLF) patients. Hepatology. 2018;2018:S1.