Title: Predictive Role of the Albumin-Bilirubin Score in ICU Patients with Cirrhosis and Sepsis:
Insights from a Large Retrospective Cohort
Version: 0 Date: 02 May 2025
Reviewer's report:
Thank you for asking me to review the manuscript. This is a retrospective outcome study on
patients with cirrhosis and critically illness in ICU, and the prognostic role of ALBI score.
MAJOR comments:
1. The authors opted to extract data regarding organ failures for hepatic, respiratory and
cardiovascular. Can the authors explain why organ failures were restricted to these only when
other organs like renal and neurological were left out, especially when it is well known that renal
failure is the most common organ dysfunction in critically ill cirrhotic and ACLF?
2. I fully agree with the authors on collecting data on severity of organ failures, but why SOFA
instead of CLIF-C-ACLF, which is validated for patients with cirrhosis and has better diagnostic
performance than SOFA?
3. The authors described 2 methods of patient stratification on ALBI scores, where the 2nd
method is based on median ALBI score. However, the authors only reported the outcomes based
on median in the supplementary material, without any discussion in the main segment of the
manuscript. Regardless of method of stratification, the higher the ALBI scores, the worse the
outcome. What then, is the relevance of stratification by the median, in regard to the main aim
of the study?
4. Although the comparison of 28- and 90-day survival between the tertiles of ALBI scores were
very significantly different, it seems the difference between T1 and T2 is small (and may not be
significant?) as shown in Table 2 and Figure 2. This is also borne out in the Cox proportional
hazards regression with all 3 models, where only T3 group was statistically significant (Table
3). Can the authors perform pairwise comparisons, either based on mortality rate at 28- and 90-
day in Table 2 or KM curves in Figure 2 to distinguish mortality risk among the groups? Please
highlight any interesting findings from this.
5. In the Cox proportional hazards analysis, how did the authors select variables for Model 2
and 3? Please describe this under Methods. If the authors performed initial univariate analysis
for the purpose of variable selection, please show this in Table 3 as well.
6. The restricted cubic spline analysis seems to also support point 4 above. What was the
threshold for increased mortality risk for 28- and 90-day mortality? And did this threshold
correspond with the cut-off ALBI for T3?
7. The Forrest plot subgroup analysis, the interaction p-value for DM was 0.01. This variable
was the only statistically significant variable with interaction, but the authors did not mention
this. Please clarify.
8. Under paragraph 5 of discussion, the authors assert that "even slight increase in the ALBI
score could significantly elevate the risk of death".  This is incorrect based on RCS analysis as
mortality risk increases with a rising ALBI score only when the threshold was exceeded but not
at lower ALBI values.
MINOR comments:
1. Figure 1 is a CONSORT diagram, not just a flowchart.
2. Table 2 is very long and difficult to follow. It is better to split Table 2 in a few smaller tables,
if permitted by the journal limit.
3. There are some errors in Figure 2 and 3. Figure 2 shows the KM curves but also includes the
CONSORT diagram while Figure 3 is the RCS but also includes the KM curves.
Title: Predictive Role of the Albumin-Bilirubin Score in ICU Patients with Cirrhosis and Sepsis:
Insights from a Large Retrospective Cohort
Version: 0 Date: 02 May 2025
Reviewer's report:
Thank you for asking me to review the manuscript. This is a retrospective outcome study on
patients with cirrhosis and critically illness in ICU, and the prognostic role of ALBI score.
MAJOR comments:
1. The authors opted to extract data regarding organ failures for hepatic, respiratory and
cardiovascular. Can the authors explain why organ failures were restricted to these only when
other organs like renal and neurological were left out, especially when it is well known that renal
failure is the most common organ dysfunction in critically ill cirrhotic and ACLF?
2. I fully agree with the authors on collecting data on severity of organ failures, but why SOFA
instead of CLIF-C-ACLF, which is validated for patients with cirrhosis and has better diagnostic
performance than SOFA?
3. The authors described 2 methods of patient stratification on ALBI scores, where the 2nd
method is based on median ALBI score. However, the authors only reported the outcomes based
on median in the supplementary material, without any discussion in the main segment of the
manuscript. Regardless of method of stratification, the higher the ALBI scores, the worse the
outcome. What then, is the relevance of stratification by the median, in regard to the main aim
of the study?
4. Although the comparison of 28- and 90-day survival between the tertiles of ALBI scores were
very significantly different, it seems the difference between T1 and T2 is small (and may not be
significant?) as shown in Table 2 and Figure 2. This is also borne out in the Cox proportional
hazards regression with all 3 models, where only T3 group was statistically significant (Table
3). Can the authors perform pairwise comparisons, either based on mortality rate at 28- and 90-
day in Table 2 or KM curves in Figure 2 to distinguish mortality risk among the groups? Please
highlight any interesting findings from this.
5. In the Cox proportional hazards analysis, how did the authors select variables for Model 2
and 3? Please describe this under Methods. If the authors performed initial univariate analysis
for the purpose of variable selection, please show this in Table 3 as well.
6. The restricted cubic spline analysis seems to also support point 4 above. What was the
threshold for increased mortality risk for 28- and 90-day mortality? And did this threshold
correspond with the cut-off ALBI for T3?
7. The Forrest plot subgroup analysis, the interaction p-value for DM was 0.01. This variable
was the only statistically significant variable with interaction, but the authors did not mention
this. Please clarify.
8. Under paragraph 5 of discussion, the authors assert that "even slight increase in the ALBI
score could significantly elevate the risk of death".  This is incorrect based on RCS analysis as
mortality risk increases with a rising ALBI score only when the threshold was exceeded but not
at lower ALBI values.
MINOR comments:
1. Figure 1 is a CONSORT diagram, not just a flowchart.
2. Table 2 is very long and difficult to follow. It is better to split Table 2 in a few smaller tables,
if permitted by the journal limit.
3. There are some errors in Figure 2 and 3. Figure 2 shows the KM curves but also includes the
CONSORT diagram while Figure 3 is the RCS but also includes the KM curves.
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: 0 Date: 02 May 2025
Reviewer's report:
Thank you for asking me to review the manuscript. This is a retrospective outcome study on
patients with cirrhosis and critically illness in ICU, and the prognostic role of ALBI score.
MAJOR comments:
1. The authors opted to extract data regarding organ failures for hepatic, respiratory and
cardiovascular. Can the authors explain why organ failures were restricted to these only when
other organs like renal and neurological were left out, especially when it is well known that renal
failure is the most common organ dysfunction in critically ill cirrhotic and ACLF?
2. I fully agree with the authors on collecting data on severity of organ failures, but why SOFA
instead of CLIF-C-ACLF, which is validated for patients with cirrhosis and has better diagnostic
performance than SOFA?
3. The authors described 2 methods of patient stratification on ALBI scores, where the 2nd
method is based on median ALBI score. However, the authors only reported the outcomes based
on median in the supplementary material, without any discussion in the main segment of the
manuscript. Regardless of method of stratification, the higher the ALBI scores, the worse the
outcome. What then, is the relevance of stratification by the median, in regard to the main aim
of the study?
4. Although the comparison of 28- and 90-day survival between the tertiles of ALBI scores were
very significantly different, it seems the difference between T1 and T2 is small (and may not be
significant?) as shown in Table 2 and Figure 2. This is also borne out in the Cox proportional
hazards regression with all 3 models, where only T3 group was statistically significant (Table
3). Can the authors perform pairwise comparisons, either based on mortality rate at 28- and 90-
day in Table 2 or KM curves in Figure 2 to distinguish mortality risk among the groups? Please
highlight any interesting findings from this.
5. In the Cox proportional hazards analysis, how did the authors select variables for Model 2
and 3? Please describe this under Methods. If the authors performed initial univariate analysis
for the purpose of variable selection, please show this in Table 3 as well.
6. The restricted cubic spline analysis seems to also support point 4 above. What was the
threshold for increased mortality risk for 28- and 90-day mortality? And did this threshold
correspond with the cut-off ALBI for T3?
7. The Forrest plot subgroup analysis, the interaction p-value for DM was 0.01. This variable
was the only statistically significant variable with interaction, but the authors did not mention
this. Please clarify.
8. Under paragraph 5 of discussion, the authors assert that "even slight increase in the ALBI
score could significantly elevate the risk of death".  This is incorrect based on RCS analysis as
mortality risk increases with a rising ALBI score only when the threshold was exceeded but not
at lower ALBI values.
MINOR comments:
1. Figure 1 is a CONSORT diagram, not just a flowchart.
2. Table 2 is very long and difficult to follow. It is better to split Table 2 in a few smaller tables,
if permitted by the journal limit.
3. There are some errors in Figure 2 and 3. Figure 2 shows the KM curves but also includes the
CONSORT diagram while Figure 3 is the RCS but also includes the KM curves.
assistant