Body composition and short-term mortality in patients critically ill with acute-on-chronic liver failure

Abstract

Background & aims: Body composition is sex dependent and associated with an increased mortality risk in patients with cirrhosis. We evaluated whether it was also associated with short-term mortality in patients critically ill with acute-on-chronic liver failure (ACLF).

Patients and methods: We retrospectively included all patients with cirrhosis and ACLF hospitalised in the intensive care unit (ICU) of Lausanne University Hospital between 2010 and 2019 for whom an abdominal computed tomography (CT) scan performed ±7 days from admission was available. Patients from the ICU of Paul Brousse University Hospital admitted between 2017 and 2020 served as an external cohort. All body composition parameters at the third lumbar vertebral level (L3) were quantified using a deep learning-based method.

Results: In total, 192 patients from Lausanne were included. Median age was 62 years and 28-day survival rate was 58.2%. In males, variables independently associated with 28-day mortality on days 1 and 3 were Chronic Liver Failure Consortium (CLIF-C) ACLF-lactate and sarcopenia. In females, CLIF-C ACLF-lactate on days 1 and 3 was the only predictor of 28-day survival. We derived two scores combining sarcopenia and the CLIF-C ACLF-lactate score on days 1 and 3, with area under the receiver operating characteristic outperforming the CLIF-C ACLF-lactate score alone in male but not in female patients. Comparable results were found in the external cohort of 58 patients and supported the sex specificity of the performance of the model. Patients with sarcopenia had increased risks of invasive fungal infection and renal replacement therapy.

Conclusion: Sarcopenia was associated with 28-day mortality in male but not in female patients critically ill with ACLF. Although screening for sarcopenia could impact the management of male patients, further studies are needed in female cohorts to investigate whether other body composition parameters are associated with outcomes.

Impact and implications: Body composition, easily assessed by CT, is altered in patients with cirrhosis and associated with outcome; it has never been investigated in patients critically ill with ACLF. The results of the present study, underlining the benefit of sarcopenia evaluation to improve prognosis prediction in males critically ill with ACLF, are of importance for physicians managing such patients to optimise the decision-making process toward continued treatment, liver transplantation, or limitation of care. In a wider sense, besides the number and course of organ failures, the results recall the weight of the general condition of males with ACLF at admission to ICU. In females critically ill with ACLF, in analyses limited by the sample size, none of the body composition parameters was associated with short-term mortality independently of organ failures; this suggests that the number and course of organ failures are the main determinant of mortality in these patients.

Keywords: Acute-on-chronic liver failure; Body composition; Cirrhosis; Computed tomography; Intensive care medicine; Sarcopenia; Skeletal muscle index; Subcutaneous adipose tissue radiation attenuation; Visceral-on-subcutaneous adipose tissue ratio.

Graphical abstract

Fig. 1

Performance of the available and newly developed models (Model d1 and d3) in the overall Lausanne cohort. (A) Receiver operating characteristic curves for survival at 28 days in the overall cohort as determined by the Chronic Liver Failure Consortium (CLIF-C) acute-on-chronic liver failure (ACLF)-lactate-sarcopenia score on Day 1 (Model d1, 0.83 [95% CI 0.76–0.88]) and Day 3 (Model d3, 0.92 [95% CI 0.86–0.95]) vs. the CLIF-C ACLF-lactate score at Day 1 (0.76 [95% CI 0.68–0.83], p = 0.004) and Day 3 (0.88 [95% CI 0.81–0.92], p = 0.006). (B) The 28-day Kaplan–Meier survival analysis of the overall cohort according to the CLIF-C ACLF-lactate-sarcopenia score at Day 1 (Model d1, cut-off ≤0.49). (C) 28-day Kaplan–Meier survival analysis of the overall cohort according to the CLIF-C ACLF-lactate-sarcopenia score at Day 3 (Model d3, cut-off ≤0.71). The 28-day survival was estimated using the Kaplan–Meier method and compared with the log-rank test. Survival was expressed as a percentage with 95% CI. The differences in terms of diagnostic accuracy between the models and the CLIF-C ACLF-lactate score on Days 1 and 3 were assessed by comparison of area under the receiver operating characteristic curves using the z test described by Zhou et al.

Fig. 2

28-day Kaplan–Meier survival analysis of the overall Lausanne cohort according to the Model d1 (cut-off ≤ 0.49) and acute-on-chronic liver failure (ACLF) (A) grade 1, (B) grade 2, and (C) grade 3. The 28-day Kaplan–Meier survival analysis of the overall cohort according to the Model d3 (cut-off ≤0.71) and ACLF (D) grade 1, (E) grade 2, and (F) grade 3. The 28-day survival was estimated using the Kaplan–Meier method and compared with the log-rank test. Survival was expressed as a percentage with 95% CI.

Fig. 3

Performance of the available and newly developed models (Model d1 and d3) in the external Villejuif cohort. (A) Receiver operating characteristic curves for survival at 28 days in the overall cohort as determined by the Chronic Liver Failure Consortium (CLIF-C) acute-on-chronic liver failure (ACLF)-lactate-sarcopenia score at Day 1 (Model d1, 0.68 [95% CI 0.55–0.81]) and Day 3 (Model d3, 0.75 [95% CI 0.62–0.83]) vs. the CLIF-C ACLF-lactate score at Day 1 (0.61 [95%CI 0.44–0.74], p = 0.07) and Day 3 (0.72 [95% CI 0.56-0.81], p = 0.14). (B) The 28-day Kaplan–Meier survival analysis of the overall cohort according to the CLIF-C ACLF-lactate-sarcopenia score at Day 1 (Model d1, cut-off ≤0.49). (C) The 28-day Kaplan–Meier survival analysis of the overall cohort according to the CLIF-C ACLF-lactate-sarcopenia score at Day 3 (Model d3, cut-off ≤0.71). The 28-day survival was estimated using the Kaplan–Meier method and compared with the log-rank test. Survival was expressed as a percentage with 95% CI. The differences in terms of diagnostic accuracy between the models and the CLIF-C ACLF-lactate score on Days 1 and 3 were assessed by comparison of area under the receiver operating characteristic curves using the z test described by Zhou et al.