Acute-on-chronic liver failure (ACLF): the 'Kyoto Consensus'-steps from Asia

Abstract

Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the 'Golden Therapeutic Window', the 'transplant window', and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The 'Kyoto APASL Consensus' presented below carries the final recommendations along with the relevant background information and areas requiring future studies.

Keywords: AARC; ACLF; Acute decompensation (AD); Cirrhosis; Non-acute decompensation (NAD); Organ failure; Recompensation.

Fig. 1

Natural History and Outcomes of CLD and cirrhosis based on hepatic reserve, nature and degree of acute insult. Abbreviations: OF- organ failure, EHOF- extrahepatic organ failure, NAD- non-acute decompensation

Fig. 2

The spectrum of liver injury and liver failure in a patient of Cirrhosis

Fig. 3

Recompensation of Cirrhosis after ACLF syndrome or Acute Decompensation

Fig. 4

The concept of hepatic reserve and reversal, regression of ACLF and the “ACLF Again”

Fig. 5

Organ Dysfunction (OD) and Organ Failure (OF) in ACLF

Fig. 6

Managing ACLF with AKI

Fig. 7

Proposal for Unified ACLF Definition (Kyoto Consensus)

Fig. 8

Etiology of ACLF in Asia–Pacific

Fig. 9

a Acute Portal Hypertension syndrome in ACLF, its progression, course and clinical outcomes ACLF. and its course in ACLF. b Clinical outcomes in ACLF based on high (> 20 mm Hg) HVPG levels. c Reduction in mortality with carvedilol compared to placebo in patients with ACLF. Abbreviations: PP- Portal Pressure, SVR- Systemic Vascular Resistance, MAP- Mean Arterial Pressure, RAAS- Renin Angiotensin Aldosterone System, PRA- Plasma Renin Activity, SNS- Sympathetic Nervous System, CO- Cardiac Output, PHT- Portal Hypertension

Fig. 10

Paracentesis induced circulatory dysfunction (PICD) and relevance of Modest Volume Paracentesis in ACLF

Fig. 11

Algorhtmic approach to the management of hepatic encephalopathy in ACLF

Fig. 12

Point of Care Ultrasound (POCUS) in the management of ACLF patients

Fig. 13

The time frame, Golden window for medical management and Liver Transplant Decision in ACLF

Fig. 14

AARC score as a guide to assess predictor of steroid response and mortality in patients with alcohol-ACLF

Fig. 15

Liver Transplant outcomes of ACLF stratified by AARC score

Fig. 16

Algorithmic Management of ACLF, based on the use of AARC score in a dynamic fashion and presence or recovery from organ failure