# Development and patterns of acute-on-chronic liver failure in patients with cirrhosis and acute kidney injury

## TL;DR

This study shows that patients with cirrhosis and acute kidney injury are at high risk of developing acute-on-chronic liver failure, with significant short-term mortality.

## Contribution

The study identifies HRS-AKI and other AKI types as strong predictors of ACLF development and progression in cirrhosis patients.

## Key findings

- 40% of patients without ACLF at AKI diagnosis later developed ACLF, often involving renal, respiratory, and liver failure.
- HRS-AKI and mixed AKI types were independently associated with higher ACLF development and progression risks.
- Respiratory failure was the most frequent extrarenal organ failure in ACLF patients.

## Abstract

The prevalence and evolution of acute-on-chronic liver failure (ACLF), particularly extrarenal organ failures, in patients with cirrhosis and acute kidney injury (AKI) are not well characterized. This study investigated the development and progression of ACLF in patients with cirrhosis who develop AKI, aiming to improve understanding of disease course during the critical period following AKI onset.

We conducted a retrospective cohort study of hospitalized patients with cirrhosis and AKI at two tertiary centers between 2010 and 2023. Data on AKI etiology, treatment, ACLF development and progression, and survival were collected. Multivariable regression models were used to assess associations between baseline and AKI-related characteristics, ACLF outcomes, and mortality.

A total of 672 patients (71% male) were included. AKI progression or non-response to therapy occurred in 47% of patients. ACLF was present at the time of AKI diagnosis in 406 patients (60%); among these, 106 (26%) experienced ACLF progression, predominantly involving renal, respiratory, and circulatory failure. Of the 266 patients without ACLF at AKI diagnosis (40%), 101 (38%) subsequently developed ACLF, most commonly with renal, respiratory, and liver failure. In multivariable analysis, patients with hepatorenal syndrome-AKI (HRS-AKI) or other/mixed AKI etiologies had a higher risk of ACLF development compared to those with pre-renal AKI (odds ratio [OR] 9.67, 95% CI 3.96–23.57; OR 4.98, 95% CI 1.78–12.95, respectively). HRS-AKI and AKI stage 2 were independently associated with ACLF progression after adjustment for MELD score and relevant clinical risk factors (OR 2.31, 95% CI 1.08–4.95; OR 2.35, 95% CI 1.03–5.36). The cumulative incidence of death was 47% at 90 days after AKI diagnosis (95% CI 44–51).

Patients with cirrhosis who develop AKI are at high risk of ACLF development and mortality. Respiratory failure is the most frequent extrarenal organ failure among patients who develop ACLF or experience ACLF progression.

This study highlights the significant risk of acute-on-chronic liver failure development in patients with cirrhosis and acute kidney injury (AKI), particularly in those with hepatorenal syndrome-AKI or other/mixed types of AKI. Given the high short-term mortality observed, early recognition and risk stratification of AKI in cirrhosis are crucial. These findings are particularly relevant for hepatologists, nephrologists, and intensivists, as they underscore the need for improved therapeutic strategies targeting AKI non-responders. Future prospective studies should not only explore targeted interventions to improve outcomes in this high-risk population but also aim to elucidate the underlying pathophysiology driving AKI progression and acute-on-chronic liver failure development in patients with cirrhosis and AKI.

Image 1

•AKI in cirrhosis is associated with short-term ACLF development and mortality.•HRS-AKI was associated with an increased risk of ACLF development and progression.•Respiratory and circulatory failure are common organ failures in patients with AKI and ACLF.•Early identification and new strategies are needed to improve outcomes in patients with cirrhosis and AKI.

AKI in cirrhosis is associated with short-term ACLF development and mortality.

HRS-AKI was associated with an increased risk of ACLF development and progression.

Respiratory and circulatory failure are common organ failures in patients with AKI and ACLF.

Early identification and new strategies are needed to improve outcomes in patients with cirrhosis and AKI.