Reviewer’s report
Title: 
Diagnostic accuracy assessment of molecular prediction model for the risk
of NAFLD based on MRI-PDFF diagnosed Chinese Han population
Version: 
0 
Date: 
22 Aug 2020
Reviewer: 
Rajarshi Banerjee
Reviewer's report:
Overall, nice, well executed study comparing an existing algorithm for assessing
likelihood of NAFLD with a new algorithm and benchmarking against NAFLD.
I congratulate the authors.
Introduction
Page 4
Line 17 - would be worthwhile referencing the superior performance of PDFF
measured with IDEAL (Hernando et al, Reeder group in Wisconsin) versus
simple PDFF. In reference 25, which appears in results, you use a specific PDFF
cutoff of 6.4% - this should be justified here.
Line 46 'In fact, the MRI-PDFF examination is expensive and the machine is
unattainable.' This needs referencing and context, as in US and EU MRI is cost-
effective versus other methods (Blake et al, BMJ Open 2016). As this is for the
Han population, approximate local pricing and ideally cost-effectiveness data
should be added, ideally in a couple of sentences contrasting them with the liver
biopsy diagnostic pathway. Access to MRI may be the biggest issue, more so
even than cost. Number of scanners per 100,000 people would be a useful
statistic.
https://bmjopen.bmj.com/content/bmjopen/6/9/e010507.full.pdf
Methods
Page 6 line 24
Participants with a MRI-PDFF value ≥ 6.4% was diagnosed as the NAFLD
patients [25]
Results
Youden Index - I think this is the correct approach
When presenting numbers/results, take care that they are not overly precise eg
only report BMI to one decimal place (page 7, line 34 'BMI value was
significant higher in the NAFLD group (28.25 ± 4.07) than in the health group
(25.14 ± 3.98) (P < 0.001)'). Likewise AUROC should be to 2 significant figures
only. 
I think the purpose of the model is to be sensitive to disease, so it would be
useful to have the cutoff which would have the same sensitivity (86% reported
by Kotronen), and report this from the AUROC curve. This would allow easier
comparison
Discussion
This is neatly written, but would benefit from three additional sentences/short
paragraghs for context. 
1. How is NAFLD thought to be different in the Han population?
2. How is current care delivered for suspected NAFLD in Qingdao?
3. How do the authors feel this molecular prediction model will be used?
Community assessment and then triaging for MRI? 
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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
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Do you hold or are you currently applying for any patents relating to the
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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: 
Diagnostic accuracy assessment of molecular prediction model for the risk
of NAFLD based on MRI-PDFF diagnosed Chinese Han population
Version: 
0 
Date: 
22 Aug 2020
Reviewer: 
Rajarshi Banerjee
Reviewer's report:
Overall, nice, well executed study comparing an existing algorithm for assessing
likelihood of NAFLD with a new algorithm and benchmarking against NAFLD.
I congratulate the authors.
Introduction
Page 4
Line 17 - would be worthwhile referencing the superior performance of PDFF
measured with IDEAL (Hernando et al, Reeder group in Wisconsin) versus
simple PDFF. In reference 25, which appears in results, you use a specific PDFF
cutoff of 6.4% - this should be justified here.
Line 46 'In fact, the MRI-PDFF examination is expensive and the machine is
unattainable.' This needs referencing and context, as in US and EU MRI is cost-
effective versus other methods (Blake et al, BMJ Open 2016). As this is for the
Han population, approximate local pricing and ideally cost-effectiveness data
should be added, ideally in a couple of sentences contrasting them with the liver
biopsy diagnostic pathway. Access to MRI may be the biggest issue, more so
even than cost. Number of scanners per 100,000 people would be a useful
statistic.
https://bmjopen.bmj.com/content/bmjopen/6/9/e010507.full.pdf
Methods
Page 6 line 24
Participants with a MRI-PDFF value ≥ 6.4% was diagnosed as the NAFLD
patients [25]
Results
Youden Index - I think this is the correct approach
When presenting numbers/results, take care that they are not overly precise eg
only report BMI to one decimal place (page 7, line 34 'BMI value was
significant higher in the NAFLD group (28.25 ± 4.07) than in the health group
(25.14 ± 3.98) (P < 0.001)'). Likewise AUROC should be to 2 significant figures
only. 
I think the purpose of the model is to be sensitive to disease, so it would be
useful to have the cutoff which would have the same sensitivity (86% reported
by Kotronen), and report this from the AUROC curve. This would allow easier
comparison
Discussion
This is neatly written, but would benefit from three additional sentences/short
paragraghs for context. 
1. How is NAFLD thought to be different in the Han population?
2. How is current care delivered for suspected NAFLD in Qingdao?
3. How do the authors feel this molecular prediction model will be used?
Community assessment and then triaging for MRI? 
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 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: 
Diagnostic accuracy assessment of molecular prediction model for the risk
of NAFLD based on MRI-PDFF diagnosed Chinese Han population
Version: 
0 
Date: 
22 Aug 2020
Reviewer: 
Rajarshi Banerjee
Reviewer's report:
Overall, nice, well executed study comparing an existing algorithm for assessing
likelihood of NAFLD with a new algorithm and benchmarking against NAFLD.
I congratulate the authors.
Introduction
Page 4
Line 17 - would be worthwhile referencing the superior performance of PDFF
measured with IDEAL (Hernando et al, Reeder group in Wisconsin) versus
simple PDFF. In reference 25, which appears in results, you use a specific PDFF
cutoff of 6.4% - this should be justified here.
Line 46 'In fact, the MRI-PDFF examination is expensive and the machine is
unattainable.' This needs referencing and context, as in US and EU MRI is cost-
effective versus other methods (Blake et al, BMJ Open 2016). As this is for the
Han population, approximate local pricing and ideally cost-effectiveness data
should be added, ideally in a couple of sentences contrasting them with the liver
biopsy diagnostic pathway. Access to MRI may be the biggest issue, more so
even than cost. Number of scanners per 100,000 people would be a useful
statistic.
https://bmjopen.bmj.com/content/bmjopen/6/9/e010507.full.pdf
Methods
Page 6 line 24
Participants with a MRI-PDFF value ≥ 6.4% was diagnosed as the NAFLD
patients [25]
Results
Youden Index - I think this is the correct approach
When presenting numbers/results, take care that they are not overly precise eg
only report BMI to one decimal place (page 7, line 34 'BMI value was
significant higher in the NAFLD group (28.25 ± 4.07) than in the health group
(25.14 ± 3.98) (P < 0.001)'). Likewise AUROC should be to 2 significant figures
only. 
I think the purpose of the model is to be sensitive to disease, so it would be
useful to have the cutoff which would have the same sensitivity (86% reported
by Kotronen), and report this from the AUROC curve. This would allow easier
comparison
Discussion
This is neatly written, but would benefit from three additional sentences/short
paragraghs for context. 
1. How is NAFLD thought to be different in the Han population?
2. How is current care delivered for suspected NAFLD in Qingdao?
3. How do the authors feel this molecular prediction model will be used?
Community assessment and then triaging for MRI? 
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 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
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