Title: Predictive Role of the Albumin-Bilirubin Score in ICU Patients with Cirrhosis and Sepsis:
Insights from a Large Retrospective Cohort
Version: 1 Date: 25 May 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
1. Lack of Novelty or Limited Incremental Value
The ALBI score has been previously evaluated in various contexts of liver disease and critical
illness. While its application in ICU patients with cirrhosis and sepsis may be novel, the
manuscript does not convincingly highlight how this study substantially advances the field.
Emphasize what makes this application unique compared to prior uses (e.g., new cutoff points,
dynamic risk stratification, integration into ICU workflows).
2. Absence of External Validation
The findings are based solely on retrospective data from a single-center database (MIMIC-IV),
limiting generalizability. Include a discussion on the lack of external validation and suggest that
further prospective or multi-center studies are needed.
3. Comparisons with MELD and SOFA Are Underdeveloped
While the manuscript claims ALBI performed comparably to SOFA, there is no rigorous
statistical comparison (e.g., the Delong test for AUC differences). Provide statistical
comparisons between the predictive abilities of ALBI, SOFA, and MELD (e.g., net
reclassification improvement, integrated discrimination improvement).
4. Potential Confounding Variables Not Fully Addressed
The adjustment strategy, although tiered (Models 1–3), may miss key confounders such
as lactate, INR, or baseline liver disease severity (e.g., compensated vs decompensated
cirrhosis).Justify the selection of variables included in multivariate models more explicitly or
perform sensitivity analyses.
5. Handling of Missing Data Could Introduce Bias
The manuscript uses multiple imputations but does not report the proportion of missingness
per variable or assess imputation accuracy.Add a table showing missingness percentages and
explain imputation diagnostics (e.g., distribution before/after imputation, number of iterations,
convergence).
6. Overinterpretation of Non-Linear Relationship
The RCS analysis shows non-linearity, but the discussion extrapolates too much into mechanistic
pathways without direct evidence.Temper mechanistic speculations and clarify that these
hypotheses will be tested in future work.
7. Outcome Definitions Lack Clarity
The definitions of 28-day and 90-day mortality need clarification (e.g., in-hospital only? post-
discharge tracked?).Clearly define how mortality data were obtained and whether post-discharge
deaths are captured.
8. Subgroup Analysis Could Be Underpowered
Subgroup analysis by sex, comorbidities, etc., is mentioned but lacks detailed results (e.g.,
interaction p-values).Include a supplementary figure or table for subgroup results with
confidence intervals and interaction tests.
9. Clinical Implementation Lacks Practical Detail
While the simplicity of ALBI is emphasized, there is no guidance on its clinical thresholds or
how it might influence decision-making.Suggest actionable thresholds or integration pathways
(e.g., triage decisions, ICU transfer, escalation of care).
10. Language and Redundancy
The manuscript is generally well-written but verbose in several sections (particularly
Discussion). Streamline the Discussion by removing repetitive statements and focusing on the
most impactful interpretations.
Title: Predictive Role of the Albumin-Bilirubin Score in ICU Patients with Cirrhosis and Sepsis:
Insights from a Large Retrospective Cohort
Version: 1 Date: 25 May 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
1. Lack of Novelty or Limited Incremental Value
The ALBI score has been previously evaluated in various contexts of liver disease and critical
illness. While its application in ICU patients with cirrhosis and sepsis may be novel, the
manuscript does not convincingly highlight how this study substantially advances the field.
Emphasize what makes this application unique compared to prior uses (e.g., new cutoff points,
dynamic risk stratification, integration into ICU workflows).
2. Absence of External Validation
The findings are based solely on retrospective data from a single-center database (MIMIC-IV),
limiting generalizability. Include a discussion on the lack of external validation and suggest that
further prospective or multi-center studies are needed.
3. Comparisons with MELD and SOFA Are Underdeveloped
While the manuscript claims ALBI performed comparably to SOFA, there is no rigorous
statistical comparison (e.g., the Delong test for AUC differences). Provide statistical
comparisons between the predictive abilities of ALBI, SOFA, and MELD (e.g., net
reclassification improvement, integrated discrimination improvement).
4. Potential Confounding Variables Not Fully Addressed
The adjustment strategy, although tiered (Models 1–3), may miss key confounders such
as lactate, INR, or baseline liver disease severity (e.g., compensated vs decompensated
cirrhosis).Justify the selection of variables included in multivariate models more explicitly or
perform sensitivity analyses.
5. Handling of Missing Data Could Introduce Bias
The manuscript uses multiple imputations but does not report the proportion of missingness
per variable or assess imputation accuracy.Add a table showing missingness percentages and
explain imputation diagnostics (e.g., distribution before/after imputation, number of iterations,
convergence).
6. Overinterpretation of Non-Linear Relationship
The RCS analysis shows non-linearity, but the discussion extrapolates too much into mechanistic
pathways without direct evidence.Temper mechanistic speculations and clarify that these
hypotheses will be tested in future work.
7. Outcome Definitions Lack Clarity
The definitions of 28-day and 90-day mortality need clarification (e.g., in-hospital only? post-
discharge tracked?).Clearly define how mortality data were obtained and whether post-discharge
deaths are captured.
8. Subgroup Analysis Could Be Underpowered
Subgroup analysis by sex, comorbidities, etc., is mentioned but lacks detailed results (e.g.,
interaction p-values).Include a supplementary figure or table for subgroup results with
confidence intervals and interaction tests.
9. Clinical Implementation Lacks Practical Detail
While the simplicity of ALBI is emphasized, there is no guidance on its clinical thresholds or
how it might influence decision-making.Suggest actionable thresholds or integration pathways
(e.g., triage decisions, ICU transfer, escalation of care).
10. Language and Redundancy
The manuscript is generally well-written but verbose in several sections (particularly
Discussion). Streamline the Discussion by removing repetitive statements and focusing on the
most impactful interpretations.
Please review this paper.
user
Title: Predictive Role of the Albumin-Bilirubin Score in ICU Patients with Cirrhosis and Sepsis:
Insights from a Large Retrospective Cohort
Version: 1 Date: 25 May 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
1. Lack of Novelty or Limited Incremental Value
The ALBI score has been previously evaluated in various contexts of liver disease and critical
illness. While its application in ICU patients with cirrhosis and sepsis may be novel, the
manuscript does not convincingly highlight how this study substantially advances the field.
Emphasize what makes this application unique compared to prior uses (e.g., new cutoff points,
dynamic risk stratification, integration into ICU workflows).
2. Absence of External Validation
The findings are based solely on retrospective data from a single-center database (MIMIC-IV),
limiting generalizability. Include a discussion on the lack of external validation and suggest that
further prospective or multi-center studies are needed.
3. Comparisons with MELD and SOFA Are Underdeveloped
While the manuscript claims ALBI performed comparably to SOFA, there is no rigorous
statistical comparison (e.g., the Delong test for AUC differences). Provide statistical
comparisons between the predictive abilities of ALBI, SOFA, and MELD (e.g., net
reclassification improvement, integrated discrimination improvement).
4. Potential Confounding Variables Not Fully Addressed
The adjustment strategy, although tiered (Models 1–3), may miss key confounders such
as lactate, INR, or baseline liver disease severity (e.g., compensated vs decompensated
cirrhosis).Justify the selection of variables included in multivariate models more explicitly or
perform sensitivity analyses.
5. Handling of Missing Data Could Introduce Bias
The manuscript uses multiple imputations but does not report the proportion of missingness
per variable or assess imputation accuracy.Add a table showing missingness percentages and
explain imputation diagnostics (e.g., distribution before/after imputation, number of iterations,
convergence).
6. Overinterpretation of Non-Linear Relationship
The RCS analysis shows non-linearity, but the discussion extrapolates too much into mechanistic
pathways without direct evidence.Temper mechanistic speculations and clarify that these
hypotheses will be tested in future work.
7. Outcome Definitions Lack Clarity
The definitions of 28-day and 90-day mortality need clarification (e.g., in-hospital only? post-
discharge tracked?).Clearly define how mortality data were obtained and whether post-discharge
deaths are captured.
8. Subgroup Analysis Could Be Underpowered
Subgroup analysis by sex, comorbidities, etc., is mentioned but lacks detailed results (e.g.,
interaction p-values).Include a supplementary figure or table for subgroup results with
confidence intervals and interaction tests.
9. Clinical Implementation Lacks Practical Detail
While the simplicity of ALBI is emphasized, there is no guidance on its clinical thresholds or
how it might influence decision-making.Suggest actionable thresholds or integration pathways
(e.g., triage decisions, ICU transfer, escalation of care).
10. Language and Redundancy
The manuscript is generally well-written but verbose in several sections (particularly
Discussion). Streamline the Discussion by removing repetitive statements and focusing on the
most impactful interpretations.
assistant