Reviewer ’s report  
 
Title: Elevated D -dimer is Assoc iated with Increased 28 -day Mortality in Acute -on-Chronic 
Liver Failure in China: a Retrospective Study  
 
Version: 1 Date: 31 Jul 2018  
 
Reviewer: giovanni capretti  
 
Reviewer's report:  
 
Dear authors,  
 
 
 
first I want to thank you for the opportunity to review your interesting work.  
 
You clearly state the drawbacks of your study design and consider them in your conclusions; this 
in my opinion is of a paramou nt importance in any proper scientific paper.  
 
 
Still your work, as it is, can raise some questions:  
 
- of your 192 patients that meets the APASL ACLF criteria 65 were excluded because the 
D-Dimer wasn't measured at the admission. 34% is a big percentage of l ost cases. You 
should provide an analysis or demonstrate that this patients were theoretically similar to 
the cohort you analyzed; otherwise you could have a fundamental selection bias. I 
provide you an example, if the 65 cases without the d -dimer are the ones admitted in a 
specific clinical setting or in specific condition or peculiar clinical scenarios this can 
mislead you evaluation providing the data of a subpopulation and not on your real 
patients' population  
 
 
- of great support to your conclusions could be an external validation cohort of your 
findings or at least and internal one (e.g. with a bootstrap).  
 
 
- 115 cases could statistically support an extended multivariate analysis such as your 
adjusted models; I h ave some concerns if the evaluations of adjusted Odds ratios for 28 -
day mortality per unit increase in D -dimer in subgroups of patients could still have any 
statistical validity. In some cases you performe a multivariate analysis on subpopulation 
of 30 or less patients  
 
 
- the D -Dimer levels correlate in your analysis with a wide spectrum of severity scores and 
prognostic elements. Have you performe any test to assess how much it's measure can 
add to the already present elements/scores?  
 
 
Please argument on th ese topics.  
 
 
Best regards  
 
 
 
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.  
 
Yes 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy 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 follo wing questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat 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 of 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 com peting 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 interests  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or 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 in my named report  can be in cluded as confidential comments 
to the editor s, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Elevated D -dimer is Assoc iated with Increased 28 -day Mortality in Acute -on-Chronic 
Liver Failure in China: a Retrospective Study  
 
Version: 1 Date: 31 Jul 2018  
 
Reviewer: giovanni capretti  
 
Reviewer's report:  
 
Dear authors,  
 
 
 
first I want to thank you for the opportunity to review your interesting work.  
 
You clearly state the drawbacks of your study design and consider them in your conclusions; this 
in my opinion is of a paramou nt importance in any proper scientific paper.  
 
 
Still your work, as it is, can raise some questions:  
 
- of your 192 patients that meets the APASL ACLF criteria 65 were excluded because the 
D-Dimer wasn't measured at the admission. 34% is a big percentage of l ost cases. You 
should provide an analysis or demonstrate that this patients were theoretically similar to 
the cohort you analyzed; otherwise you could have a fundamental selection bias. I 
provide you an example, if the 65 cases without the d -dimer are the ones admitted in a 
specific clinical setting or in specific condition or peculiar clinical scenarios this can 
mislead you evaluation providing the data of a subpopulation and not on your real 
patients' population  
 
 
- of great support to your conclusions could be an external validation cohort of your 
findings or at least and internal one (e.g. with a bootstrap).  
 
 
- 115 cases could statistically support an extended multivariate analysis such as your 
adjusted models; I h ave some concerns if the evaluations of adjusted Odds ratios for 28 -
day mortality per unit increase in D -dimer in subgroups of patients could still have any 
statistical validity. In some cases you performe a multivariate analysis on subpopulation 
of 30 or less patients  
 
 
- the D -Dimer levels correlate in your analysis with a wide spectrum of severity scores and 
prognostic elements. Have you performe any test to assess how much it's measure can 
add to the already present elements/scores?  
 
 
Please argument on th ese topics.  
 
 
Best regards  
 
 
 
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.  
 
Yes 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy 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 follo wing questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat 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 of 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 com peting 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 interests  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or 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 in my named report  can be in cluded as confidential comments 
to the editor s, 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: Elevated D -dimer is Assoc iated with Increased 28 -day Mortality in Acute -on-Chronic 
Liver Failure in China: a Retrospective Study  
 
Version: 1 Date: 31 Jul 2018  
 
Reviewer: giovanni capretti  
 
Reviewer's report:  
 
Dear authors,  
 
 
 
first I want to thank you for the opportunity to review your interesting work.  
 
You clearly state the drawbacks of your study design and consider them in your conclusions; this 
in my opinion is of a paramou nt importance in any proper scientific paper.  
 
 
Still your work, as it is, can raise some questions:  
 
- of your 192 patients that meets the APASL ACLF criteria 65 were excluded because the 
D-Dimer wasn't measured at the admission. 34% is a big percentage of l ost cases. You 
should provide an analysis or demonstrate that this patients were theoretically similar to 
the cohort you analyzed; otherwise you could have a fundamental selection bias. I 
provide you an example, if the 65 cases without the d -dimer are the ones admitted in a 
specific clinical setting or in specific condition or peculiar clinical scenarios this can 
mislead you evaluation providing the data of a subpopulation and not on your real 
patients' population  
 
 
- of great support to your conclusions could be an external validation cohort of your 
findings or at least and internal one (e.g. with a bootstrap).  
 
 
- 115 cases could statistically support an extended multivariate analysis such as your 
adjusted models; I h ave some concerns if the evaluations of adjusted Odds ratios for 28 -
day mortality per unit increase in D -dimer in subgroups of patients could still have any 
statistical validity. In some cases you performe a multivariate analysis on subpopulation 
of 30 or less patients  
 
 
- the D -Dimer levels correlate in your analysis with a wide spectrum of severity scores and 
prognostic elements. Have you performe any test to assess how much it's measure can 
add to the already present elements/scores?  
 
 
Please argument on th ese topics.  
 
 
Best regards  
 
 
 
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.  
 
Yes 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy 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 follo wing questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat 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 of 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 com peting 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 interests  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or 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 in my named report  can be in cluded as confidential comments 
to the editor s, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant