Reviewer’s report
Title: 
Association of HSD17B13 rs72613567: TA allelic variant with liver
disease: review and meta-analysis
Version: 
1 
Date: 
14 Jul 2021
Reviewer: 
Citrawati Dyah Kencono Wungu
Reviewer's report:
Please include all comments for the authors in this box rather than uploading
your report as an attachment. Please only upload as attachments annotated
versions of manuscripts, graphs, supporting materials or other aspects of your
report which cannot be included in a text format.
Please overwrite this text when adding your comments to the authors.
This manuscript studied the association of HSD17B13 rs72613567: TA allelic
variant with liver disease. THe topic is actually pretty interesting; however, there
are some major concerns that 
should be fixed:
1. There has been a similar meta-analysis before (with more detailed
explanation): 10.26355/eurrev_202009_22842. Please highlight the novelty of
this current paper to raise its interest for the readers.
2. OR less than 1 means that it has lower risk. In this study, it means TA allelic
variant will decrease the risk of HCC (OR=0.766 and 0.649), or protective
against HCC, not the opposite. Thus, there has been a major misinterpretation
here, as the authors stated that HSD17B13 rs7261356:TA allelic variant was
associated with HCC risk.
3. The term CLD here should be specified, as HCC itself should have been part
of CLD. Is it chronic hepatitis, liver cirrhosis, or what condition?
4. The article is lacking explanation regarding HSD17B13 rs7261356:TA allelic
variant itself. Please describe the gene, polymorphism type, and its role and how
it is related to liver disease.
Where is its location in gene(intron/exon, number)? How about its mechanism?
What is the role of the protein? How many alleles does it have?
5. In the inclusion criteria, CLD, HCC, NAFLD, and AFLD definitions and
diagnosis criteria should be added. Language restriction, duplication, and age
limitation of the participants should also be added. It is also mentioned in the
inclusion criteria: "if two (or more) studies included the same cohort..." Whereas
all of the included studies were case control.
6. There is no risk of bias assessment in this manuscript, in which it is a
compulsory thing that should be performed in a systematic review/meta-analysis.
7. Many important informastion are not presented in the table of study
characteristic, for example:(1) Matching variables/adjustment of confounding
factors; (2) mean age of the participants; (3) The presence of hepatitis virus
infection or other HCC etiology/risk factors; (4) What does non NAFLD here
means? Is it any liver disease other NAFLD or ALD? 
8. There should be at least two genetic model analysis for this polymorphism:
additive and allelic model, while in this study, only 1 model was performed.
9. The discussion is so lacking. The mechanism of rs7261356:TA allelic variant
to HSD17B13 protein and how it affects HCC should be explained molecularly.
Explain also the metabolism involved on HCC and NAFLD.
10. How does the result connect with the existing theories? How is the result of
the current study compared to previous studies? Benefit and future prospectives?
11. Why did the authors only include case control but not cohort study type? 
12. More limitation of this study should be added, for example: this study only
included case control. Besides, there are also many confounding factors which
contribute to HCC and NAFLD, e.g. other polymorphisms, smoking, alcohol,
age, gender, hepatitis virus infection, etc
13. As the discussion is lacking, we also suggest the authors to read and add
more references to the studies.
There are also some minor comments:
1. The number of included studies should be written in words, not number. For
example, it should be "five studies", instead of "5 studies"
2. There are some grammatical errors that should be fixed. The author should
proofread the manuscript.
3. In the exclusion criteria, it is stated: "no-case-control study". Does it mean
studies other than case control study design?
4. Describe the developer of the software used.
5. In Table 1, Europe is a continent, not country. Please mention the specific
countries
6. There is no citation of Stickel.F 2019 in Table 1.
7. Hardy-Weinberg equilibrium test should be performed.
8. In Table 2, please describe the number of studies in each group.
Publons Reviewer Recognition
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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?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Association of HSD17B13 rs72613567: TA allelic variant with liver
disease: review and meta-analysis
Version: 
1 
Date: 
14 Jul 2021
Reviewer: 
Citrawati Dyah Kencono Wungu
Reviewer's report:
Please include all comments for the authors in this box rather than uploading
your report as an attachment. Please only upload as attachments annotated
versions of manuscripts, graphs, supporting materials or other aspects of your
report which cannot be included in a text format.
Please overwrite this text when adding your comments to the authors.
This manuscript studied the association of HSD17B13 rs72613567: TA allelic
variant with liver disease. THe topic is actually pretty interesting; however, there
are some major concerns that 
should be fixed:
1. There has been a similar meta-analysis before (with more detailed
explanation): 10.26355/eurrev_202009_22842. Please highlight the novelty of
this current paper to raise its interest for the readers.
2. OR less than 1 means that it has lower risk. In this study, it means TA allelic
variant will decrease the risk of HCC (OR=0.766 and 0.649), or protective
against HCC, not the opposite. Thus, there has been a major misinterpretation
here, as the authors stated that HSD17B13 rs7261356:TA allelic variant was
associated with HCC risk.
3. The term CLD here should be specified, as HCC itself should have been part
of CLD. Is it chronic hepatitis, liver cirrhosis, or what condition?
4. The article is lacking explanation regarding HSD17B13 rs7261356:TA allelic
variant itself. Please describe the gene, polymorphism type, and its role and how
it is related to liver disease.
Where is its location in gene(intron/exon, number)? How about its mechanism?
What is the role of the protein? How many alleles does it have?
5. In the inclusion criteria, CLD, HCC, NAFLD, and AFLD definitions and
diagnosis criteria should be added. Language restriction, duplication, and age
limitation of the participants should also be added. It is also mentioned in the
inclusion criteria: "if two (or more) studies included the same cohort..." Whereas
all of the included studies were case control.
6. There is no risk of bias assessment in this manuscript, in which it is a
compulsory thing that should be performed in a systematic review/meta-analysis.
7. Many important informastion are not presented in the table of study
characteristic, for example:(1) Matching variables/adjustment of confounding
factors; (2) mean age of the participants; (3) The presence of hepatitis virus
infection or other HCC etiology/risk factors; (4) What does non NAFLD here
means? Is it any liver disease other NAFLD or ALD? 
8. There should be at least two genetic model analysis for this polymorphism:
additive and allelic model, while in this study, only 1 model was performed.
9. The discussion is so lacking. The mechanism of rs7261356:TA allelic variant
to HSD17B13 protein and how it affects HCC should be explained molecularly.
Explain also the metabolism involved on HCC and NAFLD.
10. How does the result connect with the existing theories? How is the result of
the current study compared to previous studies? Benefit and future prospectives?
11. Why did the authors only include case control but not cohort study type? 
12. More limitation of this study should be added, for example: this study only
included case control. Besides, there are also many confounding factors which
contribute to HCC and NAFLD, e.g. other polymorphisms, smoking, alcohol,
age, gender, hepatitis virus infection, etc
13. As the discussion is lacking, we also suggest the authors to read and add
more references to the studies.
There are also some minor comments:
1. The number of included studies should be written in words, not number. For
example, it should be "five studies", instead of "5 studies"
2. There are some grammatical errors that should be fixed. The author should
proofread the manuscript.
3. In the exclusion criteria, it is stated: "no-case-control study". Does it mean
studies other than case control study design?
4. Describe the developer of the software used.
5. In Table 1, Europe is a continent, not country. Please mention the specific
countries
6. There is no citation of Stickel.F 2019 in Table 1.
7. Hardy-Weinberg equilibrium test should be performed.
8. In Table 2, please describe the number of studies in each group.
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?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
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: 
Association of HSD17B13 rs72613567: TA allelic variant with liver
disease: review and meta-analysis
Version: 
1 
Date: 
14 Jul 2021
Reviewer: 
Citrawati Dyah Kencono Wungu
Reviewer's report:
Please include all comments for the authors in this box rather than uploading
your report as an attachment. Please only upload as attachments annotated
versions of manuscripts, graphs, supporting materials or other aspects of your
report which cannot be included in a text format.
Please overwrite this text when adding your comments to the authors.
This manuscript studied the association of HSD17B13 rs72613567: TA allelic
variant with liver disease. THe topic is actually pretty interesting; however, there
are some major concerns that 
should be fixed:
1. There has been a similar meta-analysis before (with more detailed
explanation): 10.26355/eurrev_202009_22842. Please highlight the novelty of
this current paper to raise its interest for the readers.
2. OR less than 1 means that it has lower risk. In this study, it means TA allelic
variant will decrease the risk of HCC (OR=0.766 and 0.649), or protective
against HCC, not the opposite. Thus, there has been a major misinterpretation
here, as the authors stated that HSD17B13 rs7261356:TA allelic variant was
associated with HCC risk.
3. The term CLD here should be specified, as HCC itself should have been part
of CLD. Is it chronic hepatitis, liver cirrhosis, or what condition?
4. The article is lacking explanation regarding HSD17B13 rs7261356:TA allelic
variant itself. Please describe the gene, polymorphism type, and its role and how
it is related to liver disease.
Where is its location in gene(intron/exon, number)? How about its mechanism?
What is the role of the protein? How many alleles does it have?
5. In the inclusion criteria, CLD, HCC, NAFLD, and AFLD definitions and
diagnosis criteria should be added. Language restriction, duplication, and age
limitation of the participants should also be added. It is also mentioned in the
inclusion criteria: "if two (or more) studies included the same cohort..." Whereas
all of the included studies were case control.
6. There is no risk of bias assessment in this manuscript, in which it is a
compulsory thing that should be performed in a systematic review/meta-analysis.
7. Many important informastion are not presented in the table of study
characteristic, for example:(1) Matching variables/adjustment of confounding
factors; (2) mean age of the participants; (3) The presence of hepatitis virus
infection or other HCC etiology/risk factors; (4) What does non NAFLD here
means? Is it any liver disease other NAFLD or ALD? 
8. There should be at least two genetic model analysis for this polymorphism:
additive and allelic model, while in this study, only 1 model was performed.
9. The discussion is so lacking. The mechanism of rs7261356:TA allelic variant
to HSD17B13 protein and how it affects HCC should be explained molecularly.
Explain also the metabolism involved on HCC and NAFLD.
10. How does the result connect with the existing theories? How is the result of
the current study compared to previous studies? Benefit and future prospectives?
11. Why did the authors only include case control but not cohort study type? 
12. More limitation of this study should be added, for example: this study only
included case control. Besides, there are also many confounding factors which
contribute to HCC and NAFLD, e.g. other polymorphisms, smoking, alcohol,
age, gender, hepatitis virus infection, etc
13. As the discussion is lacking, we also suggest the authors to read and add
more references to the studies.
There are also some minor comments:
1. The number of included studies should be written in words, not number. For
example, it should be "five studies", instead of "5 studies"
2. There are some grammatical errors that should be fixed. The author should
proofread the manuscript.
3. In the exclusion criteria, it is stated: "no-case-control study". Does it mean
studies other than case control study design?
4. Describe the developer of the software used.
5. In Table 1, Europe is a continent, not country. Please mention the specific
countries
6. There is no citation of Stickel.F 2019 in Table 1.
7. Hardy-Weinberg equilibrium test should be performed.
8. In Table 2, please describe the number of studies in each group.
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?
No
Is the use of statistics and treatment of uncertainties appropriate?
No
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
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