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: 24 Jan 2020  
 
Reviewer: Irene Cacciola  
 
Reviewer's report:  
 
The paper proposes to determine the capability of the Albumin infusion to reduce the risk of 
rebleeding and mortality in cirrhotic patients admitted in -hospital for acute gastrointestinal 
bleeding (GIB). The topic is certainly important the identification of new indications for the use 
of human Albumin infusion is a relevant issue. The use of albumin infusion is approved only in 
few clinical conditions such as: large volumes of paracentesis and hypoalbuminemia; in 
spontaneous peritonitis bacterial and in he patorenal syndrome, despite it is been known that 
albumin has important "non oncotic" properties. The paper as it now stands is not ready to be 
published, as there are important aspects to be re -analysed in the work.  
Major comments  
1. Study design: This re trospective study evaluates patients admitted to the hospital over a 
long time range (Jan 2009 to Dec 2018) for GIB including patients with hepatocellular 
carcinoma (HCC) or portal vein thrombosis (PVT) that are themselves conditions that cause an 
increase  of portal hypertension and represent important risk factors for GIB. It would be more 
appropriate to exclude those patients from the study.  
2. Study design: The presence of ascites and encephalopathy, concomitant medication, 
and number of patients who wer e under albumin treatment before the hospitalization is not 
included the baseline records. Please include this important information.  
3. Infusion of albumin and red blood cell: The indication of use of albumin is unclear.  
How many patients with compensate d cirrhosis and albumin normal value (Child Pugh Class A) 
received albumin infusion? What are the indications?  
4. Results: A total of 2239 cirrhotic patients were included in this analysis. Of them 414 
had HCC and 407 had PTV, how many patients has both th e complications?  
5. Results: The authors indicate that "…. 208 patients did not receive endoscopy 
interventions because of massive haemorrhage with rapid deterioration conditions" Those 
patients should not be considered in the statistical analyses as the a im of the study was to" 
investigate whether the albumin infusion would affect the prognosis of cirrhotic patients".  
6. The association between albumin/RBC infusion for in -patient rebleeding: the inclusion 
of patients in different class of Child Pugh in mul tivariate analyses, could be lead to an incorrect 
interpretation of the data. It is clear that patients with decompensated cirrhosis had a worse 
outcome. The focus is  determine whether the administration of albumin can improve the 
outcome of cirrhotic pat ients or not. It would be more appropriate, therefore, to perform three 
different multivariate analyses for patients in class A, B or C respectively.  
In addition, the authors should list the patients on the bases of albumin level at hospital 
admission ( &gt;3.5 gr dl and &lt; 3.5 gr dl), and evaluate the outcome on the basis of the 
albumin infusions. In the reviewer opinion, all the above selection bias might compromise the 
validity of the research results. According to the above major comments the paper i s not 
recommended for publication.  
 
 
Are the methods appropriate and well  described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
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 recommend additional statistical review  
 
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: 24 Jan 2020  
 
Reviewer: Irene Cacciola  
 
Reviewer's report:  
 
The paper proposes to determine the capability of the Albumin infusion to reduce the risk of 
rebleeding and mortality in cirrhotic patients admitted in -hospital for acute gastrointestinal 
bleeding (GIB). The topic is certainly important the identification of new indications for the use 
of human Albumin infusion is a relevant issue. The use of albumin infusion is approved only in 
few clinical conditions such as: large volumes of paracentesis and hypoalbuminemia; in 
spontaneous peritonitis bacterial and in he patorenal syndrome, despite it is been known that 
albumin has important "non oncotic" properties. The paper as it now stands is not ready to be 
published, as there are important aspects to be re -analysed in the work.  
Major comments  
1. Study design: This re trospective study evaluates patients admitted to the hospital over a 
long time range (Jan 2009 to Dec 2018) for GIB including patients with hepatocellular 
carcinoma (HCC) or portal vein thrombosis (PVT) that are themselves conditions that cause an 
increase  of portal hypertension and represent important risk factors for GIB. It would be more 
appropriate to exclude those patients from the study.  
2. Study design: The presence of ascites and encephalopathy, concomitant medication, 
and number of patients who wer e under albumin treatment before the hospitalization is not 
included the baseline records. Please include this important information.  
3. Infusion of albumin and red blood cell: The indication of use of albumin is unclear.  
How many patients with compensate d cirrhosis and albumin normal value (Child Pugh Class A) 
received albumin infusion? What are the indications?  
4. Results: A total of 2239 cirrhotic patients were included in this analysis. Of them 414 
had HCC and 407 had PTV, how many patients has both th e complications?  
5. Results: The authors indicate that "…. 208 patients did not receive endoscopy 
interventions because of massive haemorrhage with rapid deterioration conditions" Those 
patients should not be considered in the statistical analyses as the a im of the study was to" 
investigate whether the albumin infusion would affect the prognosis of cirrhotic patients".  
6. The association between albumin/RBC infusion for in -patient rebleeding: the inclusion 
of patients in different class of Child Pugh in mul tivariate analyses, could be lead to an incorrect 
interpretation of the data. It is clear that patients with decompensated cirrhosis had a worse 
outcome. The focus is  determine whether the administration of albumin can improve the 
outcome of cirrhotic pat ients or not. It would be more appropriate, therefore, to perform three 
different multivariate analyses for patients in class A, B or C respectively.  
In addition, the authors should list the patients on the bases of albumin level at hospital 
admission ( &gt;3.5 gr dl and &lt; 3.5 gr dl), and evaluate the outcome on the basis of the 
albumin infusions. In the reviewer opinion, all the above selection bias might compromise the 
validity of the research results. According to the above major comments the paper i s not 
recommended for publication.  
 
 
Are the methods appropriate and well  described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
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 recommend additional statistical review  
 
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: 24 Jan 2020  
 
Reviewer: Irene Cacciola  
 
Reviewer's report:  
 
The paper proposes to determine the capability of the Albumin infusion to reduce the risk of 
rebleeding and mortality in cirrhotic patients admitted in -hospital for acute gastrointestinal 
bleeding (GIB). The topic is certainly important the identification of new indications for the use 
of human Albumin infusion is a relevant issue. The use of albumin infusion is approved only in 
few clinical conditions such as: large volumes of paracentesis and hypoalbuminemia; in 
spontaneous peritonitis bacterial and in he patorenal syndrome, despite it is been known that 
albumin has important "non oncotic" properties. The paper as it now stands is not ready to be 
published, as there are important aspects to be re -analysed in the work.  
Major comments  
1. Study design: This re trospective study evaluates patients admitted to the hospital over a 
long time range (Jan 2009 to Dec 2018) for GIB including patients with hepatocellular 
carcinoma (HCC) or portal vein thrombosis (PVT) that are themselves conditions that cause an 
increase  of portal hypertension and represent important risk factors for GIB. It would be more 
appropriate to exclude those patients from the study.  
2. Study design: The presence of ascites and encephalopathy, concomitant medication, 
and number of patients who wer e under albumin treatment before the hospitalization is not 
included the baseline records. Please include this important information.  
3. Infusion of albumin and red blood cell: The indication of use of albumin is unclear.  
How many patients with compensate d cirrhosis and albumin normal value (Child Pugh Class A) 
received albumin infusion? What are the indications?  
4. Results: A total of 2239 cirrhotic patients were included in this analysis. Of them 414 
had HCC and 407 had PTV, how many patients has both th e complications?  
5. Results: The authors indicate that "…. 208 patients did not receive endoscopy 
interventions because of massive haemorrhage with rapid deterioration conditions" Those 
patients should not be considered in the statistical analyses as the a im of the study was to" 
investigate whether the albumin infusion would affect the prognosis of cirrhotic patients".  
6. The association between albumin/RBC infusion for in -patient rebleeding: the inclusion 
of patients in different class of Child Pugh in mul tivariate analyses, could be lead to an incorrect 
interpretation of the data. It is clear that patients with decompensated cirrhosis had a worse 
outcome. The focus is  determine whether the administration of albumin can improve the 
outcome of cirrhotic pat ients or not. It would be more appropriate, therefore, to perform three 
different multivariate analyses for patients in class A, B or C respectively.  
In addition, the authors should list the patients on the bases of albumin level at hospital 
admission ( &gt;3.5 gr dl and &lt; 3.5 gr dl), and evaluate the outcome on the basis of the 
albumin infusions. In the reviewer opinion, all the above selection bias might compromise the 
validity of the research results. According to the above major comments the paper i s not 
recommended for publication.  
 
 
Are the methods appropriate and well  described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
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 recommend additional statistical review  
 
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