Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update

Abstract

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the “APASL ACLF Research Consortium (AARC)” was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the ‘Golden Therapeutic Window’, extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here.

Viral Hepatitis Other than A, B, and C

“…33 Additionally, HEV has been recognized as a cause of acute on chronic liver failure worldwide. 34 Chronic HEV, defined by chronic hepatitis with elevated aminotransferase levels and persistent detection of HEV RNA for six months after exposure, is rare in immunocompetent individuals but has been increasingly recognized with genotype 3 HEV infections in immunocompromised hosts, particularly in those with solid organ transplants (SOT), stem cell transplants (SCT), or human immunodeficiency virus (HIV). This is likely due to the impaired and/or insufficient immune T-cell response with an inability to control the virus in the immunocompromised state.…”

Letter to the Editor: Tale of Two ACLF Definitions: Choices Are Getting Clearer

“…We read the study by Mahmud et al that applies Asian Pacific Association for the Study of the Liver (APASL) (1) and European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) (2) acute-on-chronic liver failure (ACLF) definitions to a large cohort of patients. The median bilirubin and creatinine at presentation in the EASL-defined cohort were around 2 mg/dL each, and the 28-day mortality was 37%.…”

“…This thought should help in early identification of liver-directed therapies, such as transplant, that might influence outcomes. (1,4) We would like to draw attention to another concept from the APASL definition (i.e., of a therapeutic "golden window" of 1 week) ( Fig. 1): the time between inflammation and development of systemic inflammatory response syndrome and sepsis.…”

“…1): the time between inflammation and development of systemic inflammatory response syndrome and sepsis. (1) The APASL-ACLF research Consortium (AARC) score is a dynamic, simple, bedside tool to prognosticate and guide the treatment (Table 1). It would be worthwhile to test the AARC score in the Western cohort of patients with hepatic ACLF.…”

“…Acute-on chronic liver failure (ACLF) is characterized by sudden worsening attributed to an acute event superimposed on chronic liver disease and is associated with organ failure and significant short-term mortality. (1) ACLF not responding to medical treatment in early course is associated with poor spontaneous survival in the absence of liver transplantation. (2) There are important differences in the definitions of ACLF given by the Asian Pacific Association for the Study of the Liver (APASL) and the European Association for the Study of the Liver (EASL).…”