Title: Association of alkaline phosphatase to albumin ratio with all-cause mortality in critically
ill patients with cirrhosis: a retrospective study
Version: 1 Date: 28 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-As a retrospective study, the data are observational, and while the MIMIC-IV database is
comprehensive, it’s not possible to establish causality from these results. The findings should be
interpreted with caution regarding cause-and-effect relationships, especially since many factors
influencing mortality could not be controlled for.
-While it is good practice to exclude participants with more than 20% missing data to maintain
the integrity of the study, the exclusion of patients without ALP or ALB data (467 patients)
or those with missing demographic information (450 patients) may introduce selection bias.
The study may not fully represent the overall population of cirrhotic ICU patients due to these
exclusions.
-Despite controlling for a wide array of confounders, there could be unmeasured or residual
confounding factors. For instance, the severity of liver cirrhosis, which could vary widely among
patients, may not have been fully captured in the model. Furthermore, other biomarkers or
clinical parameters that could influence mortality may not have been included.
-While the APAR calculation is clear and easy to interpret, it’s important to consider whether this
ratio fully captures the complexity of cirrhosis progression or other factors influencing mortality.
There may be a need for further validation of the APAR index in different cohorts, particularly
outside the ICU setting.
-Despite adjusting for 26 covariates, there may still be unmeasured confounders influencing the
observed relationship. For example, the role of dietary factors, medications, or lifestyle habits
could affect both APAR levels and mortality risk, but these factors may not have been fully
captured in the analysis.
-While the study examines mortality at 28, 90, and 365 days, it would be useful to explore the
time-dependent nature of the association further. Mortality risk may vary over time, and a more
detailed exploration of time-to-event survival would enhance the understanding of how APAR
influences mortality risk in the short term versus the long term.
Title: Association of alkaline phosphatase to albumin ratio with all-cause mortality in critically
ill patients with cirrhosis: a retrospective study
Version: 1 Date: 28 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-As a retrospective study, the data are observational, and while the MIMIC-IV database is
comprehensive, it’s not possible to establish causality from these results. The findings should be
interpreted with caution regarding cause-and-effect relationships, especially since many factors
influencing mortality could not be controlled for.
-While it is good practice to exclude participants with more than 20% missing data to maintain
the integrity of the study, the exclusion of patients without ALP or ALB data (467 patients)
or those with missing demographic information (450 patients) may introduce selection bias.
The study may not fully represent the overall population of cirrhotic ICU patients due to these
exclusions.
-Despite controlling for a wide array of confounders, there could be unmeasured or residual
confounding factors. For instance, the severity of liver cirrhosis, which could vary widely among
patients, may not have been fully captured in the model. Furthermore, other biomarkers or
clinical parameters that could influence mortality may not have been included.
-While the APAR calculation is clear and easy to interpret, it’s important to consider whether this
ratio fully captures the complexity of cirrhosis progression or other factors influencing mortality.
There may be a need for further validation of the APAR index in different cohorts, particularly
outside the ICU setting.
-Despite adjusting for 26 covariates, there may still be unmeasured confounders influencing the
observed relationship. For example, the role of dietary factors, medications, or lifestyle habits
could affect both APAR levels and mortality risk, but these factors may not have been fully
captured in the analysis.
-While the study examines mortality at 28, 90, and 365 days, it would be useful to explore the
time-dependent nature of the association further. Mortality risk may vary over time, and a more
detailed exploration of time-to-event survival would enhance the understanding of how APAR
influences mortality risk in the short term versus the long term.
Please review this paper.
user
Title: Association of alkaline phosphatase to albumin ratio with all-cause mortality in critically
ill patients with cirrhosis: a retrospective study
Version: 1 Date: 28 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-As a retrospective study, the data are observational, and while the MIMIC-IV database is
comprehensive, it’s not possible to establish causality from these results. The findings should be
interpreted with caution regarding cause-and-effect relationships, especially since many factors
influencing mortality could not be controlled for.
-While it is good practice to exclude participants with more than 20% missing data to maintain
the integrity of the study, the exclusion of patients without ALP or ALB data (467 patients)
or those with missing demographic information (450 patients) may introduce selection bias.
The study may not fully represent the overall population of cirrhotic ICU patients due to these
exclusions.
-Despite controlling for a wide array of confounders, there could be unmeasured or residual
confounding factors. For instance, the severity of liver cirrhosis, which could vary widely among
patients, may not have been fully captured in the model. Furthermore, other biomarkers or
clinical parameters that could influence mortality may not have been included.
-While the APAR calculation is clear and easy to interpret, it’s important to consider whether this
ratio fully captures the complexity of cirrhosis progression or other factors influencing mortality.
There may be a need for further validation of the APAR index in different cohorts, particularly
outside the ICU setting.
-Despite adjusting for 26 covariates, there may still be unmeasured confounders influencing the
observed relationship. For example, the role of dietary factors, medications, or lifestyle habits
could affect both APAR levels and mortality risk, but these factors may not have been fully
captured in the analysis.
-While the study examines mortality at 28, 90, and 365 days, it would be useful to explore the
time-dependent nature of the association further. Mortality risk may vary over time, and a more
detailed exploration of time-to-event survival would enhance the understanding of how APAR
influences mortality risk in the short term versus the long term.
assistant