Reviewer’s report
Title: 
Plasma interleukin-17 and alpha-fetoprotein combination effectively predicts imminent
hepatocellular carcinoma occurrence in liver cirrhotic patients
Version: 
0 
Date: 
12 Oct 2020
Reviewer's report:
This paper by Liang et al., titled "Plasma interleukin-17 and alpha-fetoprotein combination effectively
predicts imminent hepatocellular carcinoma occurrence in liver cirrhotic patients" shows that IL-17 and
AFP are good markers to predict HCC occurrence in patients using a prospective study set-up and
ELISAs. Even though IL-17 has been shown to be a prognostic factor for HCC, the authors suggest that Il-
17 can be a marker to predict HCC occurrence. I do not think that the data presented in this paper supports
the authors' conclusions and the data presented lacks novelty and applicability.
Major problems:
1. The authors state: "Thus, IL-17 is an independent biomarker, rather than a surrogate biomarker of other
common clinical variables at the liver cirrhosis stage." : I do not think correlations between IL-17 and
other clinical and serological markers can tell the authors whether IL-17 is an independent marker a the
liver cirrhosis stage. 
2. Figure 1: how was "Probability of HCC" calculated? Where do these numbers come from?
3. Figure 1: The same data should be shown for AFP to compare how AFP compared to IL-17 in
predicting HCC occurrence.
4. Figure 2: only data for IL-17 is shown. Data should be compared to AFP alone, and to other factors that
have not been shown to correlate with HCC occurrence. There is no controls shown and the data shown
may be similar for other immune markers besides IL-17. I do not see how IL-17 as oppose to other
immune markers are good predictors of HCC occurrence.
5. The authors stated: "A wealth of literature has showed the usefulness of AFP for indicating imminent
HCC". If this has been published and it was shown to be affective, why looking at IL-17? It seems to me
that AFP works great as a marker of HCC occurrence. No comparisons were made to IL-17 so it is hard to
know if IL-17 is a good marker.
6. Why aren't EGFR, FGFR, NOTCH1 and C-type lectin signaling factors which interact with IL-17 good
markers to predict HCC occurrence? There is plenty of evidence of the involvement of IL-17 in HCC. I do
not see the novelty in this paper.
Minor problems:
1. There are grammatical errors
2. Figure legends are not very descriptive of the figures
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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
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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 
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?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
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: 
Plasma interleukin-17 and alpha-fetoprotein combination effectively predicts imminent
hepatocellular carcinoma occurrence in liver cirrhotic patients
Version: 
0 
Date: 
12 Oct 2020
Reviewer's report:
This paper by Liang et al., titled "Plasma interleukin-17 and alpha-fetoprotein combination effectively
predicts imminent hepatocellular carcinoma occurrence in liver cirrhotic patients" shows that IL-17 and
AFP are good markers to predict HCC occurrence in patients using a prospective study set-up and
ELISAs. Even though IL-17 has been shown to be a prognostic factor for HCC, the authors suggest that Il-
17 can be a marker to predict HCC occurrence. I do not think that the data presented in this paper supports
the authors' conclusions and the data presented lacks novelty and applicability.
Major problems:
1. The authors state: "Thus, IL-17 is an independent biomarker, rather than a surrogate biomarker of other
common clinical variables at the liver cirrhosis stage." : I do not think correlations between IL-17 and
other clinical and serological markers can tell the authors whether IL-17 is an independent marker a the
liver cirrhosis stage. 
2. Figure 1: how was "Probability of HCC" calculated? Where do these numbers come from?
3. Figure 1: The same data should be shown for AFP to compare how AFP compared to IL-17 in
predicting HCC occurrence.
4. Figure 2: only data for IL-17 is shown. Data should be compared to AFP alone, and to other factors that
have not been shown to correlate with HCC occurrence. There is no controls shown and the data shown
may be similar for other immune markers besides IL-17. I do not see how IL-17 as oppose to other
immune markers are good predictors of HCC occurrence.
5. The authors stated: "A wealth of literature has showed the usefulness of AFP for indicating imminent
HCC". If this has been published and it was shown to be affective, why looking at IL-17? It seems to me
that AFP works great as a marker of HCC occurrence. No comparisons were made to IL-17 so it is hard to
know if IL-17 is a good marker.
6. Why aren't EGFR, FGFR, NOTCH1 and C-type lectin signaling factors which interact with IL-17 good
markers to predict HCC occurrence? There is plenty of evidence of the involvement of IL-17 in HCC. I do
not see the novelty in this paper.
Minor problems:
1. There are grammatical errors
2. Figure legends are not very descriptive of the figures
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 
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?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
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: 
Plasma interleukin-17 and alpha-fetoprotein combination effectively predicts imminent
hepatocellular carcinoma occurrence in liver cirrhotic patients
Version: 
0 
Date: 
12 Oct 2020
Reviewer's report:
This paper by Liang et al., titled "Plasma interleukin-17 and alpha-fetoprotein combination effectively
predicts imminent hepatocellular carcinoma occurrence in liver cirrhotic patients" shows that IL-17 and
AFP are good markers to predict HCC occurrence in patients using a prospective study set-up and
ELISAs. Even though IL-17 has been shown to be a prognostic factor for HCC, the authors suggest that Il-
17 can be a marker to predict HCC occurrence. I do not think that the data presented in this paper supports
the authors' conclusions and the data presented lacks novelty and applicability.
Major problems:
1. The authors state: "Thus, IL-17 is an independent biomarker, rather than a surrogate biomarker of other
common clinical variables at the liver cirrhosis stage." : I do not think correlations between IL-17 and
other clinical and serological markers can tell the authors whether IL-17 is an independent marker a the
liver cirrhosis stage. 
2. Figure 1: how was "Probability of HCC" calculated? Where do these numbers come from?
3. Figure 1: The same data should be shown for AFP to compare how AFP compared to IL-17 in
predicting HCC occurrence.
4. Figure 2: only data for IL-17 is shown. Data should be compared to AFP alone, and to other factors that
have not been shown to correlate with HCC occurrence. There is no controls shown and the data shown
may be similar for other immune markers besides IL-17. I do not see how IL-17 as oppose to other
immune markers are good predictors of HCC occurrence.
5. The authors stated: "A wealth of literature has showed the usefulness of AFP for indicating imminent
HCC". If this has been published and it was shown to be affective, why looking at IL-17? It seems to me
that AFP works great as a marker of HCC occurrence. No comparisons were made to IL-17 so it is hard to
know if IL-17 is a good marker.
6. Why aren't EGFR, FGFR, NOTCH1 and C-type lectin signaling factors which interact with IL-17 good
markers to predict HCC occurrence? There is plenty of evidence of the involvement of IL-17 in HCC. I do
not see the novelty in this paper.
Minor problems:
1. There are grammatical errors
2. Figure legends are not very descriptive of the figures
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 
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?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
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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