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Liver failure determines the outcome in patients of acute-on-chronic liver failure (ACLF): comparison of APASL ACLF research consortium (AARC) and CLIF-SOFA models

Choudhury A, Jindal A, Maiwall R, Sharma MK, Sharma BC, Pamecha V, et al.

Hepatol Int, 2017 Sep;11(5):461-471.
PMID: 28856540 DOI: 10.1007/s12072-017-9816-z

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical worsening and high mortality. Early prediction of mortality and intervention can improve patient outcomes. We aimed to develop a dynamic prognostic model and compare it with the existing models.
METHODS: A total of 1402 ACLF patients, enrolled in the APASL-ACLF Research Consortium (AARC) with 90-day follow-up, were analyzed. An ACLF score was developed in a derivation cohort (n = 480) and was validated (n = 922).
RESULTS: The overall survival of ACLF patients at 28 days was 51.7%, with a median of 26.3 days. Five baseline variables, total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy, were found to be independent predictors of mortality, with AUROC in derivation and validation cohorts being 0.80 and 0.78, respectively. AARC-ACLF score (range 5-15) was found to be superior to MELD and CLIF SOFA scores in predicting mortality with an AUROC of 0.80. The point scores were categorized into grades of liver failure (Gr I: 5-7; II: 8-10; and III: 11-15 points) with 28-day cumulative mortalities of 12.7, 44.5 and 85.9%, respectively. The mortality risk could be dynamically calculated as, with each unit increase in AARC-ACLF score above 10, the risk increased by 20%. A score of ≥11 at baseline or persisting in the first week was often seen among nonsurvivors (p = 0.001).
CONCLUSIONS: The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.
Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014

Sarin SK, Kedarisetty CK, Abbas Z, Amarapurkar D, Bihari C, Chan AC, et al.

Hepatol Int, 2014 Oct;8(4):453-71.
PMID: 26202751 DOI: 10.1007/s12072-014-9580-2

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. Due to the rapid advancements in the knowledge and available information, a consortium of members from countries across Asia Pacific, "APASL ACLF Research Consortium (AARC)," was formed in 2012. A large cohort of retrospective and prospective data of ACLF patients was collated and followed up in this data base. The current ACLF definition was reassessed based on the new AARC data base. These initiatives were concluded on a 2-day meeting in February 2014 at New Delhi and led to the development of the final AARC consensus. Only those statements which were based on the evidence and were unanimously recommended were accepted. These statements were circulated again to all the experts and subsequently presented at the annual conference of the APASL at Brisbane, on March 14, 2014. The suggestions from the delegates were analyzed by the expert panel, and the modifications in the consensus were made. The final consensus and guidelines document was prepared. After detailed deliberations and data analysis, the original proposed definition was found to withstand the test of time and identify a homogenous group of patients presenting with liver failure. Based on the AARC data, liver failure grading, and its impact on the "Golden therapeutic Window," extra-hepatic organ failure and development of sepsis were analyzed. 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 are presented here.
Systemic inflammatory response syndrome in acute-on-chronic liver failure: Relevance of 'golden window': A prospective study

Choudhury A, Kumar M, Sharma BC, Maiwall R, Pamecha V, Moreau R, et al.

J Gastroenterol Hepatol, 2017 Dec;32(12):1989-1997.
PMID: 28374414 DOI: 10.1111/jgh.13799

BACKGROUND AND AIM: Systemic inflammatory response syndrome (SIRS) is an early marker of sepsis and ongoing inflammation and has been reported in large proportion of acute-on-chronic liver failure (ACLF) patients. Whether sepsis is the cause or the result of liver failure is unclear and is vital to know. To address this, the study investigated the course and outcome of ACLF patients without SIRS/sepsis.
METHODS: Consecutive ACLF patients were monitored for the development of SIRS/sepsis and associated complications and followed till 90 days, liver transplant or death.
RESULTS: Of 561 patients, 201 (35.8%) had no SIRS and 360 (64.2%) had SIRS with or without infection. New onset SIRS and sepsis developed in 74.6% and 8% respectively in a median of 7 (range 4-15) days, at a rate of 11% per day. The cumulative incidence of new SIRS was 29%, 92.8%, and 100% by days 4, 7, and 15. Liver failure, that is, bilirubin > 12 mg/dL (odds ratio [OR] = 2.5 [95% confidence interval {CI} = 1.05-6.19], P = 0.04) at days 0 and 4, and renal failure at day 4 (OR = 6.74 [95%CI = 1.50-13.29], P = 0.01), independently predicted new onset SIRS. Absence of SIRS in the first week was associated with reduced incidence of organ failure (20% vs 39.4%, P = 0.003), as was the 28-day (17.6% vs 36%, P = 0.02) and 90-day (27.5% vs 51%,P = 0.002) mortality. The 90-day mortality was 61.6% in the total cohort and that for those having no SIRS and SIRS at presentation were 42.8% and 65%, respectively (P
Development of predisposition, injury, response, organ failure model for predicting acute kidney injury in acute on chronic liver failure

Maiwall R, Sarin SK, Kumar S, Jain P, Kumar G, Bhadoria AS, et al.

Liver Int, 2017 Oct;37(10):1497-1507.
PMID: 28393476 DOI: 10.1111/liv.13443

BACKGROUND AND AIM: There is limited data on predictors of acute kidney injury in acute on chronic liver failure. We developed a PIRO model (Predisposition, Injury, Response, Organ failure) for predicting acute kidney injury in a multicentric cohort of acute on chronic liver failure patients.
PATIENTS AND METHODS: Data of 2360 patients from APASL-ACLF Research Consortium (AARC) was analysed. Multivariate logistic regression model (PIRO score) was developed from a derivation cohort (n=1363) which was validated in another prospective multicentric cohort of acute on chronic liver failure patients (n=997).
RESULTS: Factors significant for P component were serum creatinine[(≥2 mg/dL)OR 4.52, 95% CI (3.67-5.30)], bilirubin [(<12 mg/dL,OR 1) vs (12-30 mg/dL,OR 1.45, 95% 1.1-2.63) vs (≥30 mg/dL,OR 2.6, 95% CI 1.3-5.2)], serum potassium [(<3 mmol/LOR-1) vs (3-4.9 mmol/L,OR 2.7, 95% CI 1.05-1.97) vs (≥5 mmol/L,OR 4.34, 95% CI 1.67-11.3)] and blood urea (OR 3.73, 95% CI 2.5-5.5); for I component nephrotoxic medications (OR-9.86, 95% CI 3.2-30.8); for R component,Systemic Inflammatory Response Syndrome,(OR-2.14, 95% CI 1.4-3.3); for O component, Circulatory failure (OR-3.5, 95% CI 2.2-5.5). The PIRO score predicted acute kidney injury with C-index of 0.95 and 0.96 in the derivation and validation cohort. The increasing PIRO score was also associated with mortality (P
APASL clinical practice guidelines on the management of acute kidney injury in acute-on-chronic liver failure

Maiwall R, Singh SP, Angeli P, Moreau R, Krag A, Singh V, et al.

Hepatol Int, 2024 Apr 05.
PMID: 38578541 DOI: 10.1007/s12072-024-10650-0

Acute-on-chronic liver failure (ACLF) is a syndrome that is characterized by the rapid development of organ failures predisposing these patients to a high risk of short-term early death. The main causes of organ failure in these patients are bacterial infections and systemic inflammation, both of which can be severe. For the majority of these patients, a prompt liver transplant is still the only effective course of treatment. Kidneys are one of the most frequent extrahepatic organs that are affected in patients with ACLF, since acute kidney injury (AKI) is reported in 22.8-34% of patients with ACLF. Approach and management of kidney injury could improve overall outcomes in these patients. Importantly, patients with ACLF more frequently have stage 3 AKI with a low rate of response to the current treatment modalities. The objective of the present position paper is to critically review and analyze the published data on AKI in ACLF, evolve a consensus, and provide recommendations for early diagnosis, pathophysiology, prevention, and management of AKI in patients with ACLF. In the absence of direct evidence, we propose expert opinions for guidance in managing AKI in this very challenging group of patients and focus on areas of future research. This consensus will be of major importance to all hepatologists, liver transplant surgeons, and intensivists across the globe.