Reviewer’s report
Title: 
Baseline thrombopoietin level is associated with platelet count
improvement in thrombocytopenic chronic hepatitis C patients after successful
direct-acting antiviral agent therapy
Version: 
0 
Date: 
15 Oct 2020
Reviewer's report:
It's a great pleasure to read this manuscript. This is a single-center, retrospective
study aiming to investigate the role of baseline thrombopoietin (TPO) in platelet
count improvement after successful DAA therapy. The study included 104
patients with chronic hepatitis C. The improvement of platelet count was
analyzed for correlation with the baseline TPO. This study found that platelet
increase from 110k at baseline to 118k twelve weeks after the end of treatment
and baseline TPO level was positively correlated with the improvement. This
might be the first study to focus on the predictive value of baseline TPO for the
improvement of platelet count after DAA therapy. However, I do have a few
concerns. 
Comments: 
Major: 
1. In this study, baseline TPO level predicates platelet count improvement in
chronic hepatitis C patients achieving SVR. But the improvement from 110k to
118k is not clinically significant. Checking the baseline TPO levels in patients
with mild thrombocytopenia will not have a strong impact on clinical practice
and might not be cost-effective. 
2. Patients were only followed for 12 weeks after treatment. Whether there is a
consistent platelet count improvement and whether baseline TPO can predict
long-term platelet count improvement are unclear. 
Minor: 
1. Since patients without SVR were excluded, it might be more accurate to use
the "Baseline thrombopoietin level is associated with platelet count improvement
in thrombocytopenic chronic hepatitis C patients after successful direct-acting
antiviral agent therapy" as the title. 
2. It would be great if authors could explain why using median and range instead
of mean and standard deviation for the continuous variables? As we know, the
median does not use all the information in the data and it can be shown to be less
efficient than the mean; the range doesn't give much indication of the spread of
observation about the mean. (https://www.bmj.com/about-bmj/resources-
readers/publications/statistics-square-one/2-mean-and-standard-deviation)
3. In Table 1, the percentage of patients with significant platelet count
improvement should be 42.3% (44/104), not 41.1%. 
4. Although advanced hepatic fibrosis status, FIB-4, HCC history, splenomegaly,
and ascites were not statistically significant between the two groups in this study,
which might due to a relatively small patient sample size, the group of patients
without significant platelet count improvement did show a tendency of having
more patients with advanced fibrosis and more comorbidities related to that. It
might be worthwhile to point that out. 
5. The rate of fibrosis is 62%, which is high than the rate reported by previous
studies. 
A systematic review of 111 studies analyzing the natural history of HCV
infection estimated that the prevalence of cirrhosis 20 years after infection was
16 percent (95% CI 14-19 percent) (Hepatology. 2008;48(2):418.). This high rate
was likely due to the use of the FIB4 score alone. AASLD mentioned that the
most efficient approach to fibrosis assessment is to combine direct biomarkers
and vibration-controlled transient liver elastography (Fibroscan) (Hepatology
2015 Sep;62(3):932-54.). In future studies, it will be better to include fibroscan
as part of fibrosis assessment. 
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No
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 
do not
 publish my name
with my report. (default)
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: 
Baseline thrombopoietin level is associated with platelet count
improvement in thrombocytopenic chronic hepatitis C patients after successful
direct-acting antiviral agent therapy
Version: 
0 
Date: 
15 Oct 2020
Reviewer's report:
It's a great pleasure to read this manuscript. This is a single-center, retrospective
study aiming to investigate the role of baseline thrombopoietin (TPO) in platelet
count improvement after successful DAA therapy. The study included 104
patients with chronic hepatitis C. The improvement of platelet count was
analyzed for correlation with the baseline TPO. This study found that platelet
increase from 110k at baseline to 118k twelve weeks after the end of treatment
and baseline TPO level was positively correlated with the improvement. This
might be the first study to focus on the predictive value of baseline TPO for the
improvement of platelet count after DAA therapy. However, I do have a few
concerns. 
Comments: 
Major: 
1. In this study, baseline TPO level predicates platelet count improvement in
chronic hepatitis C patients achieving SVR. But the improvement from 110k to
118k is not clinically significant. Checking the baseline TPO levels in patients
with mild thrombocytopenia will not have a strong impact on clinical practice
and might not be cost-effective. 
2. Patients were only followed for 12 weeks after treatment. Whether there is a
consistent platelet count improvement and whether baseline TPO can predict
long-term platelet count improvement are unclear. 
Minor: 
1. Since patients without SVR were excluded, it might be more accurate to use
the "Baseline thrombopoietin level is associated with platelet count improvement
in thrombocytopenic chronic hepatitis C patients after successful direct-acting
antiviral agent therapy" as the title. 
2. It would be great if authors could explain why using median and range instead
of mean and standard deviation for the continuous variables? As we know, the
median does not use all the information in the data and it can be shown to be less
efficient than the mean; the range doesn't give much indication of the spread of
observation about the mean. (https://www.bmj.com/about-bmj/resources-
readers/publications/statistics-square-one/2-mean-and-standard-deviation)
3. In Table 1, the percentage of patients with significant platelet count
improvement should be 42.3% (44/104), not 41.1%. 
4. Although advanced hepatic fibrosis status, FIB-4, HCC history, splenomegaly,
and ascites were not statistically significant between the two groups in this study,
which might due to a relatively small patient sample size, the group of patients
without significant platelet count improvement did show a tendency of having
more patients with advanced fibrosis and more comorbidities related to that. It
might be worthwhile to point that out. 
5. The rate of fibrosis is 62%, which is high than the rate reported by previous
studies. 
A systematic review of 111 studies analyzing the natural history of HCV
infection estimated that the prevalence of cirrhosis 20 years after infection was
16 percent (95% CI 14-19 percent) (Hepatology. 2008;48(2):418.). This high rate
was likely due to the use of the FIB4 score alone. AASLD mentioned that the
most efficient approach to fibrosis assessment is to combine direct biomarkers
and vibration-controlled transient liver elastography (Fibroscan) (Hepatology
2015 Sep;62(3):932-54.). In future studies, it will be better to include fibroscan
as part of fibrosis assessment. 
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 upon publication of the manuscript. 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
No
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 
do not
 publish my name
with my report. (default)
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: 
Baseline thrombopoietin level is associated with platelet count
improvement in thrombocytopenic chronic hepatitis C patients after successful
direct-acting antiviral agent therapy
Version: 
0 
Date: 
15 Oct 2020
Reviewer's report:
It's a great pleasure to read this manuscript. This is a single-center, retrospective
study aiming to investigate the role of baseline thrombopoietin (TPO) in platelet
count improvement after successful DAA therapy. The study included 104
patients with chronic hepatitis C. The improvement of platelet count was
analyzed for correlation with the baseline TPO. This study found that platelet
increase from 110k at baseline to 118k twelve weeks after the end of treatment
and baseline TPO level was positively correlated with the improvement. This
might be the first study to focus on the predictive value of baseline TPO for the
improvement of platelet count after DAA therapy. However, I do have a few
concerns. 
Comments: 
Major: 
1. In this study, baseline TPO level predicates platelet count improvement in
chronic hepatitis C patients achieving SVR. But the improvement from 110k to
118k is not clinically significant. Checking the baseline TPO levels in patients
with mild thrombocytopenia will not have a strong impact on clinical practice
and might not be cost-effective. 
2. Patients were only followed for 12 weeks after treatment. Whether there is a
consistent platelet count improvement and whether baseline TPO can predict
long-term platelet count improvement are unclear. 
Minor: 
1. Since patients without SVR were excluded, it might be more accurate to use
the "Baseline thrombopoietin level is associated with platelet count improvement
in thrombocytopenic chronic hepatitis C patients after successful direct-acting
antiviral agent therapy" as the title. 
2. It would be great if authors could explain why using median and range instead
of mean and standard deviation for the continuous variables? As we know, the
median does not use all the information in the data and it can be shown to be less
efficient than the mean; the range doesn't give much indication of the spread of
observation about the mean. (https://www.bmj.com/about-bmj/resources-
readers/publications/statistics-square-one/2-mean-and-standard-deviation)
3. In Table 1, the percentage of patients with significant platelet count
improvement should be 42.3% (44/104), not 41.1%. 
4. Although advanced hepatic fibrosis status, FIB-4, HCC history, splenomegaly,
and ascites were not statistically significant between the two groups in this study,
which might due to a relatively small patient sample size, the group of patients
without significant platelet count improvement did show a tendency of having
more patients with advanced fibrosis and more comorbidities related to that. It
might be worthwhile to point that out. 
5. The rate of fibrosis is 62%, which is high than the rate reported by previous
studies. 
A systematic review of 111 studies analyzing the natural history of HCV
infection estimated that the prevalence of cirrhosis 20 years after infection was
16 percent (95% CI 14-19 percent) (Hepatology. 2008;48(2):418.). This high rate
was likely due to the use of the FIB4 score alone. AASLD mentioned that the
most efficient approach to fibrosis assessment is to combine direct biomarkers
and vibration-controlled transient liver elastography (Fibroscan) (Hepatology
2015 Sep;62(3):932-54.). In future studies, it will be better to include fibroscan
as part of fibrosis assessment. 
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 upon publication of the manuscript. 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
No
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 
do not
 publish my name
with my report. (default)
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