Reviewer ’s report  
 
Title: The impact of albumin infusion on the risk of rebleeding and in -hospital mortality in  
cirrhotic patients admitted for acute gastrointestinal bleeding: a retrospective study of a single  
institute  
 
Version: 0 Date: 08 Mar 2020  
 
Reviewer: Stephan Haas  
 
Reviewer's report:  
 
The authors of this interesting study present the data of a large retrospective monocenter study 
including more than 2200 liver cirrhosis patients admitted to the hospita l due to upper GI 
bleeding.  
Altogether, 245 patients developed rebleeding and 135 patients died.  
Based on a multivariate analysis, albumin infusion was correlated with a lower risk for 
rebleeding and in -hospital mortality. Conversely, blood transfusion i ncreased the risk for 
rebleeding.  
 
The study is of great interest as the effect of albumin supplementation in cirrhotic patients with 
upper GI bleeding is not systematically studied.  
 
Concerning blood transfusions, the authors correctly state in their di scussion that "the causal 
relationship between pre -RBC infusion and rebleeding cannot be determined based on current 
data". Due to the retrospective study design, a causal relationship between albumin infusion and 
rebleeding and mortality cannot be made.  
The title, the conclusion and the discussion have to be modified accordingly.  
The authors should point out that prospective studies are required to answer the important 
question whether i.v. albumin reduces the risk for rebleeding and mortality.  
 
Interes tingly, even very low albumin infusions ( &lt;40 g) resulted in a drastic reduction of the 
risk of rebreeding (OR: 0.385). The authors discuss the possibility that other cofounders could be 
involved.  
 
The authors should include the specific recommendations  of current international guidelines 
regarding the timing of endoscopy.  
The UK guidelines from 2015 recommend:  
"Suggestions for timing of upper gastrointestinal endoscopy: 2.1. Offer endoscopy to unstable 
patients with severe acute upper gastrointestinal  bleeding immediately after resuscitation (level 
5, grade A). 2.2. Offer endoscopy within 24 h of admission to all other patients with upper 
gastrointestinal bleeding (level 2b, grade A). (UK guideline 2015).  
 
The authors advocate "that appropriate endosc opic therapies for variceal lesion should be given 
within 5 days as most experts suggested". References should be added for this rather long 
interval. After this statement the authors point out that " early identification of the bleeding 
lesion is crucial for the management of acute GIB" contradicting the "5 day recommendation".  
 
The authors should state more clearly, how many patients received endoscopic treatment and 
after which interval. This would be helpful for the reader ("There were 208 (9.3%) patie nts who 
did not receive endoscopy interventions").  
  
Are all radiological interventions represented by TIPS placement? This should be clarified more 
clearly. "…535 (23.9%) patients only underwent radiological interventional treatment" (without 
endoscopy?).  The authors should clarify what treatment almost one -fourth of all patients 
received.  
90.7% received endoscopy and 23.9% underwent radiological interventions? This is a very high 
percentage for TIPS!  
The numbers and percentages should be double -checked.  
 
Do the authors recommend albumin substitution irrespective of the albumin levels in cirrhotic 
patients with upper GI bleeding? Maybe this topic could be included in the discussion.  
 
 
Are the methods appropriate and well  described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the m anuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality  of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years recei ved reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content o f the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any  non-financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing i nterests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included i n my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: The impact of albumin infusion on the risk of rebleeding and in -hospital mortality in  
cirrhotic patients admitted for acute gastrointestinal bleeding: a retrospective study of a single  
institute  
 
Version: 0 Date: 08 Mar 2020  
 
Reviewer: Stephan Haas  
 
Reviewer's report:  
 
The authors of this interesting study present the data of a large retrospective monocenter study 
including more than 2200 liver cirrhosis patients admitted to the hospita l due to upper GI 
bleeding.  
Altogether, 245 patients developed rebleeding and 135 patients died.  
Based on a multivariate analysis, albumin infusion was correlated with a lower risk for 
rebleeding and in -hospital mortality. Conversely, blood transfusion i ncreased the risk for 
rebleeding.  
 
The study is of great interest as the effect of albumin supplementation in cirrhotic patients with 
upper GI bleeding is not systematically studied.  
 
Concerning blood transfusions, the authors correctly state in their di scussion that "the causal 
relationship between pre -RBC infusion and rebleeding cannot be determined based on current 
data". Due to the retrospective study design, a causal relationship between albumin infusion and 
rebleeding and mortality cannot be made.  
The title, the conclusion and the discussion have to be modified accordingly.  
The authors should point out that prospective studies are required to answer the important 
question whether i.v. albumin reduces the risk for rebleeding and mortality.  
 
Interes tingly, even very low albumin infusions ( &lt;40 g) resulted in a drastic reduction of the 
risk of rebreeding (OR: 0.385). The authors discuss the possibility that other cofounders could be 
involved.  
 
The authors should include the specific recommendations  of current international guidelines 
regarding the timing of endoscopy.  
The UK guidelines from 2015 recommend:  
"Suggestions for timing of upper gastrointestinal endoscopy: 2.1. Offer endoscopy to unstable 
patients with severe acute upper gastrointestinal  bleeding immediately after resuscitation (level 
5, grade A). 2.2. Offer endoscopy within 24 h of admission to all other patients with upper 
gastrointestinal bleeding (level 2b, grade A). (UK guideline 2015).  
 
The authors advocate "that appropriate endosc opic therapies for variceal lesion should be given 
within 5 days as most experts suggested". References should be added for this rather long 
interval. After this statement the authors point out that " early identification of the bleeding 
lesion is crucial for the management of acute GIB" contradicting the "5 day recommendation".  
 
The authors should state more clearly, how many patients received endoscopic treatment and 
after which interval. This would be helpful for the reader ("There were 208 (9.3%) patie nts who 
did not receive endoscopy interventions").  
  
Are all radiological interventions represented by TIPS placement? This should be clarified more 
clearly. "…535 (23.9%) patients only underwent radiological interventional treatment" (without 
endoscopy?).  The authors should clarify what treatment almost one -fourth of all patients 
received.  
90.7% received endoscopy and 23.9% underwent radiological interventions? This is a very high 
percentage for TIPS!  
The numbers and percentages should be double -checked.  
 
Do the authors recommend albumin substitution irrespective of the albumin levels in cirrhotic 
patients with upper GI bleeding? Maybe this topic could be included in the discussion.  
 
 
Are the methods appropriate and well  described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the m anuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality  of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years recei ved reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content o f the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any  non-financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing i nterests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included i n my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: The impact of albumin infusion on the risk of rebleeding and in -hospital mortality in  
cirrhotic patients admitted for acute gastrointestinal bleeding: a retrospective study of a single  
institute  
 
Version: 0 Date: 08 Mar 2020  
 
Reviewer: Stephan Haas  
 
Reviewer's report:  
 
The authors of this interesting study present the data of a large retrospective monocenter study 
including more than 2200 liver cirrhosis patients admitted to the hospita l due to upper GI 
bleeding.  
Altogether, 245 patients developed rebleeding and 135 patients died.  
Based on a multivariate analysis, albumin infusion was correlated with a lower risk for 
rebleeding and in -hospital mortality. Conversely, blood transfusion i ncreased the risk for 
rebleeding.  
 
The study is of great interest as the effect of albumin supplementation in cirrhotic patients with 
upper GI bleeding is not systematically studied.  
 
Concerning blood transfusions, the authors correctly state in their di scussion that "the causal 
relationship between pre -RBC infusion and rebleeding cannot be determined based on current 
data". Due to the retrospective study design, a causal relationship between albumin infusion and 
rebleeding and mortality cannot be made.  
The title, the conclusion and the discussion have to be modified accordingly.  
The authors should point out that prospective studies are required to answer the important 
question whether i.v. albumin reduces the risk for rebleeding and mortality.  
 
Interes tingly, even very low albumin infusions ( &lt;40 g) resulted in a drastic reduction of the 
risk of rebreeding (OR: 0.385). The authors discuss the possibility that other cofounders could be 
involved.  
 
The authors should include the specific recommendations  of current international guidelines 
regarding the timing of endoscopy.  
The UK guidelines from 2015 recommend:  
"Suggestions for timing of upper gastrointestinal endoscopy: 2.1. Offer endoscopy to unstable 
patients with severe acute upper gastrointestinal  bleeding immediately after resuscitation (level 
5, grade A). 2.2. Offer endoscopy within 24 h of admission to all other patients with upper 
gastrointestinal bleeding (level 2b, grade A). (UK guideline 2015).  
 
The authors advocate "that appropriate endosc opic therapies for variceal lesion should be given 
within 5 days as most experts suggested". References should be added for this rather long 
interval. After this statement the authors point out that " early identification of the bleeding 
lesion is crucial for the management of acute GIB" contradicting the "5 day recommendation".  
 
The authors should state more clearly, how many patients received endoscopic treatment and 
after which interval. This would be helpful for the reader ("There were 208 (9.3%) patie nts who 
did not receive endoscopy interventions").  
  
Are all radiological interventions represented by TIPS placement? This should be clarified more 
clearly. "…535 (23.9%) patients only underwent radiological interventional treatment" (without 
endoscopy?).  The authors should clarify what treatment almost one -fourth of all patients 
received.  
90.7% received endoscopy and 23.9% underwent radiological interventions? This is a very high 
percentage for TIPS!  
The numbers and percentages should be double -checked.  
 
Do the authors recommend albumin substitution irrespective of the albumin levels in cirrhotic 
patients with upper GI bleeding? Maybe this topic could be included in the discussion.  
 
 
Are the methods appropriate and well  described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the m anuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality  of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years recei ved reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content o f the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any  non-financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing i nterests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included i n my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant