Reviewer ’s report  
Title: Thrombin and Factor Xa Link the Coagulation System with Liver Fibrosis  
 
Version: 2 Date: 07 Dec 2017  
 
Reviewer: Christian M. Lange  
 
Reviewer's report:  
In the present study, and colleagues provide in vitro and in vivo evidence for a role of factor Xa 
(and thrombin) for hep atofibrogenesis. The manuscript is well written and of potential clinical 
importance, because at least in the murine system the authors could show that treatment of mice 
with direct anti -Xa inhibitors results in a reduction of liver fibrosis. I have only s ome minor 
comments which should be addressed:  
 
- The source and preparation of rivaroxaban and dabigatran should be indicated in the methods 
section  
- The discussion should provide a statement, whether factor Xa levels in vitro reflect 
physiological concent rations  
- The discussion should speculate on whether the observed in vivo effects are considered to be 
specific for DOACs or whether enoxaparin (a frequently used anticoagulant in liver cirrhosis) 
may or may not have comparable effects  
- The font size in s ome Figures is too small and hard to read  
 
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 supporte d 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 spe cify 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 comp lete a declaration of competing interests, considering the following 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 financially from the publication of t his 
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 apply ing 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 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 have no conflict of interest.  
 
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 in 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: Thrombin and Factor Xa Link the Coagulation System with Liver Fibrosis  
 
Version: 2 Date: 07 Dec 2017  
 
Reviewer: Christian M. Lange  
 
Reviewer's report:  
In the present study, and colleagues provide in vitro and in vivo evidence for a role of factor Xa 
(and thrombin) for hep atofibrogenesis. The manuscript is well written and of potential clinical 
importance, because at least in the murine system the authors could show that treatment of mice 
with direct anti -Xa inhibitors results in a reduction of liver fibrosis. I have only s ome minor 
comments which should be addressed:  
 
- The source and preparation of rivaroxaban and dabigatran should be indicated in the methods 
section  
- The discussion should provide a statement, whether factor Xa levels in vitro reflect 
physiological concent rations  
- The discussion should speculate on whether the observed in vivo effects are considered to be 
specific for DOACs or whether enoxaparin (a frequently used anticoagulant in liver cirrhosis) 
may or may not have comparable effects  
- The font size in s ome Figures is too small and hard to read  
 
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 supporte d 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 spe cify 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 comp lete a declaration of competing interests, considering the following 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 financially from the publication of t his 
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 apply ing 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 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 have no conflict of interest.  
 
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 in 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: Thrombin and Factor Xa Link the Coagulation System with Liver Fibrosis  
 
Version: 2 Date: 07 Dec 2017  
 
Reviewer: Christian M. Lange  
 
Reviewer's report:  
In the present study, and colleagues provide in vitro and in vivo evidence for a role of factor Xa 
(and thrombin) for hep atofibrogenesis. The manuscript is well written and of potential clinical 
importance, because at least in the murine system the authors could show that treatment of mice 
with direct anti -Xa inhibitors results in a reduction of liver fibrosis. I have only s ome minor 
comments which should be addressed:  
 
- The source and preparation of rivaroxaban and dabigatran should be indicated in the methods 
section  
- The discussion should provide a statement, whether factor Xa levels in vitro reflect 
physiological concent rations  
- The discussion should speculate on whether the observed in vivo effects are considered to be 
specific for DOACs or whether enoxaparin (a frequently used anticoagulant in liver cirrhosis) 
may or may not have comparable effects  
- The font size in s ome Figures is too small and hard to read  
 
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 supporte d 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 spe cify 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 comp lete a declaration of competing interests, considering the following 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 financially from the publication of t his 
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 apply ing 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 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 have no conflict of interest.  
 
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 in 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