Review for 10.1186/s12876-025-03926-8 (2025)

Title: The prognostic value of sarcopenia in acute-on-chronic liver failure: A systematic review
and meta-analysis
Version: 1 Date: 23 Mar 2025
Reviewer's report:
This systematic review and meta-analysis provide valuable insights into the prognostic role of
sarcopenia in patients with acute-on-chronic liver failure (ACLF)—a clinically relevant and
underexplored topic. The study is well-conducted, featuring a comprehensive literature search
and appropriate use of quality assessment tools. The findings consistently demonstrate that
sarcopenia is linked to increased short- and long-term mortality in ACLF patients.
Strengths of the Study
The study is methodologically rigorous, utilizing well-established risk-of-bias tools to ensure
the quality and reliability of the included studies. By analyzing mortality at multiple time points
—such as 28-day, 90-day, and overall mortality—the authors enhance the clinical relevance
of their findings and provide a more comprehensive view of sarcopenia's prognostic impact.
Furthermore, the low heterogeneity noted in most of the pooled estimates further strengthens
the robustness and consistency of the results across diverse study settings.
Suggestions for Improvement:
Clarify the operational definitions of sarcopenia used across the included studies. Studies
examining sarcopenia, particularly in patients with chronic liver disease or acute-on-chronic
liver failure (ACLF), find that the selection of outcomes is crucial for evaluating its clinical
impact. The most widely accepted and clinically meaningful primary outcomes encompass
mortality endpoints. These are typically reported as short-term mortality, such as 28-day or in-
hospital mortality, which is especially relevant for patients with ACLF, as well as medium- to
long-term mortality, including 90-day, 180-day, or one-year mortality. These outcomes provide
direct prognostic information and reflect the severity of the underlying liver dysfunction in the
context of muscle wasting.
Another crucial primary outcome is transplant-free survival, which combines the events of
death and liver transplantation. This is particularly valuable when assessing sarcopenia in
patients with decompensated cirrhosis or ACLF who may be awaiting liver transplantation. In
transplant recipients, post-transplant outcomes such as one-year mortality or graft survival are
also commonly studied, as sarcopenia has been shown to impact post-operative recovery and
long-term prognosis negatively.
Secondary outcomes often aim to capture sarcopenia's broader functional and clinical
implications. Hospitalization-related outcomes, including length of hospital stay, ICU stay,
and 30-day readmission rates, are frequently assessed to evaluate the burden of sarcopenia
on healthcare utilization. The incidence of complications, such as infections, hepatic
encephalopathy, or variceal bleeding, may also be considered. Functional status and quality of
life represent another important category of secondary outcomes. Health-related quality of life
(HRQoL) provides further insight into the patient’s well-being.
Additionally, nutritional status and frailty indicators are often included. Taken together,
these primary and secondary outcomes provide a comprehensive framework for evaluating
the prognostic significance of sarcopenia, its functional consequences, and its potential for
reversibility through targeted interventions. This meta-analysis did not elaborate on these points;
only primary outcome endpoints were used as parameters.
Furthermore, for the 90-day mortality, the hazard ratio of 1.66 remains statistically significant,
although substantial heterogeneity exists (I² = 72.3%). This level of heterogeneity could be
due to variations in sarcopenia definitions, imaging modalities, patient populations, or ACLF
diagnostic criteria across studies and should be elaborated on in the discussion. Sensitivity
analyses or subgroup analyses could help clarify these potential sources of variability.
Assessing publication bias is crucial. Elaborate on the clinical implications of the findings,
especially concerning the role of early nutritional or physical interventions. Lastly, specific
directions for future research should include the need for standardized diagnostic criteria and
prospective cohort studies.