Reviewer’s report
Title: 
Potential utility of a multi-component coagulation factor panel to calculate
MELD scores and assess the risk of portal vein thrombosis in chronic liver
disease
Version: 
0 
Date: 
31 Oct 2022
Reviewer: 
HAKAN AKIN
Reviewer's report:
Dear Authors,
I find your work very well organized and having solutions to some important
clinical problems for Crohic Liver disease and Liver Transplant patients. I have
some little revision requests according to the parts of the manuscript.
Best regards
Essentials Part? 
1) The statement: Portal vein thrombosis (PVT) is detected in only 50% of cases
due to imaging limitations."
Totally not stated in the manuscript. In the manuscript only 3 patients reported to
have PVT. 
Also it is not stated: What type of Imaging studies were conducted
(doppler USG, Contrast enhanced CT, etc?) to which patient and at what
protocol frequency.?
2) "Activity levels of Factor V and Protein C can be used to substitute PT/INR in
MELD scoring" 
This is an assertive statement. Although need for further studies is very well
stated all through the Results and Conclusions parts, replacement of a softer
statement like " …might have a potential to substitute PT/INR in MELD scoring
but further studies needed" will be nice.
Methods:
1) In table 1 content, Cohort A has a healthy control group included, which
should be stated in Methods part. 
2) Although stated superficially in Methods It would be nice to have the sex
distribution and etiology of CLD in the table 1 as in the table 2 which is nicely
having that details.
Results
3) Inclusion and exclusion criteria stated well in the Methods part. 
Authors indicated in the Results part that "One of the patients was diagnosed
with PVT 3 months prior to enrollment". This patient already has PVT diagnosis.
Do the authors have an explanation for this patients' data be used for the future
risk assessment of PVT in CLD patients. 
4) In the Results part, it is not stated if any/ which type of clinical, biochemical
and radiology follow-up has been done to these two Cohorts. If not please state
that in the Methods part.
5) In the Results, it is not stated: what type of imaging studies were conducted
(doppler USG, Contrast enhanced CT, etc?) as diagnostic methods the PVT
diagnosis. If so, how many of the patients had radiology follow-ups for the PVT
diagnosis
6) Do we have the data about how many of the patients had undergone liver
transplantation during study period and if any of these patients deceased.
7) Authors stated 36/43 of Cohort B is alive six months later. Any of PVT patient
died? How many if any, of these had liver transplanted?
Limitations
Authors stated the limitations of the study well as:
"Our study is limited by its modest cohort sizes, relatively low incidence of PVT,
and short-term patient outcomes (6 months)". 
They also well stated the need for further studies as:
"Large, multi-center studies are required to corroborate our approach to assess
the risk for PVT, and to further evaluate the feasibility of using FV and PC
activity levels as a substitute for PT/INR in MELD scoring, especially with
regard to the clinical outcomes.´
Publons Reviewer Recognition
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find the details of processing in Publons’ privacy policy
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Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received 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 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 declare that I have no competing interests'
Reviewer Publication Consent.
 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
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please publish my name with my
report.
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Potential utility of a multi-component coagulation factor panel to calculate
MELD scores and assess the risk of portal vein thrombosis in chronic liver
disease
Version: 
0 
Date: 
31 Oct 2022
Reviewer: 
HAKAN AKIN
Reviewer's report:
Dear Authors,
I find your work very well organized and having solutions to some important
clinical problems for Crohic Liver disease and Liver Transplant patients. I have
some little revision requests according to the parts of the manuscript.
Best regards
Essentials Part? 
1) The statement: Portal vein thrombosis (PVT) is detected in only 50% of cases
due to imaging limitations."
Totally not stated in the manuscript. In the manuscript only 3 patients reported to
have PVT. 
Also it is not stated: What type of Imaging studies were conducted
(doppler USG, Contrast enhanced CT, etc?) to which patient and at what
protocol frequency.?
2) "Activity levels of Factor V and Protein C can be used to substitute PT/INR in
MELD scoring" 
This is an assertive statement. Although need for further studies is very well
stated all through the Results and Conclusions parts, replacement of a softer
statement like " …might have a potential to substitute PT/INR in MELD scoring
but further studies needed" will be nice.
Methods:
1) In table 1 content, Cohort A has a healthy control group included, which
should be stated in Methods part. 
2) Although stated superficially in Methods It would be nice to have the sex
distribution and etiology of CLD in the table 1 as in the table 2 which is nicely
having that details.
Results
3) Inclusion and exclusion criteria stated well in the Methods part. 
Authors indicated in the Results part that "One of the patients was diagnosed
with PVT 3 months prior to enrollment". This patient already has PVT diagnosis.
Do the authors have an explanation for this patients' data be used for the future
risk assessment of PVT in CLD patients. 
4) In the Results part, it is not stated if any/ which type of clinical, biochemical
and radiology follow-up has been done to these two Cohorts. If not please state
that in the Methods part.
5) In the Results, it is not stated: what type of imaging studies were conducted
(doppler USG, Contrast enhanced CT, etc?) as diagnostic methods the PVT
diagnosis. If so, how many of the patients had radiology follow-ups for the PVT
diagnosis
6) Do we have the data about how many of the patients had undergone liver
transplantation during study period and if any of these patients deceased.
7) Authors stated 36/43 of Cohort B is alive six months later. Any of PVT patient
died? How many if any, of these had liver transplanted?
Limitations
Authors stated the limitations of the study well as:
"Our study is limited by its modest cohort sizes, relatively low incidence of PVT,
and short-term patient outcomes (6 months)". 
They also well stated the need for further studies as:
"Large, multi-center studies are required to corroborate our approach to assess
the risk for PVT, and to further evaluate the feasibility of using FV and PC
activity levels as a substitute for PT/INR in MELD scoring, especially with
regard to the clinical outcomes.´
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received 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 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 declare that I have no competing interests'
Reviewer Publication Consent.
 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
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please publish my name with my
report.
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Potential utility of a multi-component coagulation factor panel to calculate
MELD scores and assess the risk of portal vein thrombosis in chronic liver
disease
Version: 
0 
Date: 
31 Oct 2022
Reviewer: 
HAKAN AKIN
Reviewer's report:
Dear Authors,
I find your work very well organized and having solutions to some important
clinical problems for Crohic Liver disease and Liver Transplant patients. I have
some little revision requests according to the parts of the manuscript.
Best regards
Essentials Part? 
1) The statement: Portal vein thrombosis (PVT) is detected in only 50% of cases
due to imaging limitations."
Totally not stated in the manuscript. In the manuscript only 3 patients reported to
have PVT. 
Also it is not stated: What type of Imaging studies were conducted
(doppler USG, Contrast enhanced CT, etc?) to which patient and at what
protocol frequency.?
2) "Activity levels of Factor V and Protein C can be used to substitute PT/INR in
MELD scoring" 
This is an assertive statement. Although need for further studies is very well
stated all through the Results and Conclusions parts, replacement of a softer
statement like " …might have a potential to substitute PT/INR in MELD scoring
but further studies needed" will be nice.
Methods:
1) In table 1 content, Cohort A has a healthy control group included, which
should be stated in Methods part. 
2) Although stated superficially in Methods It would be nice to have the sex
distribution and etiology of CLD in the table 1 as in the table 2 which is nicely
having that details.
Results
3) Inclusion and exclusion criteria stated well in the Methods part. 
Authors indicated in the Results part that "One of the patients was diagnosed
with PVT 3 months prior to enrollment". This patient already has PVT diagnosis.
Do the authors have an explanation for this patients' data be used for the future
risk assessment of PVT in CLD patients. 
4) In the Results part, it is not stated if any/ which type of clinical, biochemical
and radiology follow-up has been done to these two Cohorts. If not please state
that in the Methods part.
5) In the Results, it is not stated: what type of imaging studies were conducted
(doppler USG, Contrast enhanced CT, etc?) as diagnostic methods the PVT
diagnosis. If so, how many of the patients had radiology follow-ups for the PVT
diagnosis
6) Do we have the data about how many of the patients had undergone liver
transplantation during study period and if any of these patients deceased.
7) Authors stated 36/43 of Cohort B is alive six months later. Any of PVT patient
died? How many if any, of these had liver transplanted?
Limitations
Authors stated the limitations of the study well as:
"Our study is limited by its modest cohort sizes, relatively low incidence of PVT,
and short-term patient outcomes (6 months)". 
They also well stated the need for further studies as:
"Large, multi-center studies are required to corroborate our approach to assess
the risk for PVT, and to further evaluate the feasibility of using FV and PC
activity levels as a substitute for PT/INR in MELD scoring, especially with
regard to the clinical outcomes.´
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received 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 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 declare that I have no competing interests'
Reviewer Publication Consent.
 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
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please publish my name with my
report.
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
assistant