Reviewer’s report
Title: 
The Prevalence of Alcoholic and Nonalcoholic Fatty Liver Disease in
Adolescents and Young Adults in the United States: Analysis of the NHANES
Database
Version: 
0 
Date: 
08 Apr 2022
Reviewer's report:
GENERAL COMMENT
This is an interesting and generally well-written paper. I have the following
comments.
MAJOR COMMENTS
Outcome measures: The Authors are to be commended for using the NHANES
survey weights for analyzing the data. I have however the following question:
how can one be sure that these data are still representative of the general US
population after the "artificial" selection based on age and the other entry criteria
is taken into account?
Discussion 1, 56: reference 5 (which has no title, see below) excluded "pediatric
cohorts". You refer to the NHANES 2008 cycle, but the reference is a systematic
review excluding young subjects.
Discussion 2, 12: referring to a generic explanation given by overviews is not
useful.
Discussion 4, 18: please explain the choice of the 248dB/m cut-point. Give a
reference to published data or quote your unpublished experience with this cut-
point.
Discussion 4, 32: why do you consider your results as "preliminary"? With the
possible limitation of the missing representativeness (which I fear is
unavoidable, and I do not consider problematic if openly addressed), your results
do not seem "preliminary" to me.
Limitations: I would expect that NHANES has produced data about the intra-
and inter-rater agreement of CAP and LSM measurements. It has certainly done
that for most of the measurements available in its databases. Please provide such
data if they are available.
Limitations: NAFLD and AFLD are differentiated only by alcohol intake, and
this complicates a lot any inference about NAFLD and alcohol intake (not to
consider the measurement error of the instruments commonly employed to
measure alcohol intake). I think—and I am surely not alone—that the overall
evidence favors no consumption of alcohol in the presence of any liver disease.
Conclusion: "dire approach to the encumbrance": I would avoid such phrasing.
Moreover, in the general population such as that studied here, most cases of fatty
liver will not "progress" to liver fibrosis. Please consider this fact in the
discussion of your results. 
Figure 1: 
please provide separately the numbers obtained after excluding by age
and by the other criteria. It would be nice to have a supplementary table
comparing the general characteristics to those with available and missing VCTE.
The missingness of alcohol consumption data is very high. You should explain
why it is so and whether you think if it can be considered random. Again, a table
comparing the general characteristics of those with and those without alcohol
data would be useful.
References: some references are lacking the title. Please check all references
carefully.
MINOR COMMENTS
Short abstract: please give the operational definition of excessive alcohol
consumption.
Abstract 1,7 and elsewhere: the word "burden" is presently (mostly) used in a
very technical sense. I suggest not using it together with prevalence. Prevalence
is more than enough. Your message is clear.
Abstract and elsewhere: please use "suspected fibrosis" as you did with
"suspected NAFLD" and "suspected FLD".
Abstract and elsewhere: I propose replacing "to be at risk of…" with "have…".
This is, in fact, a cross-sectional study. (I admit the use or risk is presently very
lax).
Background: please provide references to support the use of VCTE for the
diagnosis of liver steatosis. Is it better than liver ultrasonography? Why?
Database: it would be nice to have a web link to the dataset employed for the
present analysis.
Definitions and inclusion criteria: please explain differences between ALQ130
and ALQ121.
Discussion 1, 54: graphs 4 and 5 should be figures 4 and 5.
Discussion 3, 35: I would write "no unique pattern of liver enzymes and other
markers" (e.g., MCV).
Discussion 3, 50: I would avoid using the adjective "tremendous" as it has no
scientific value.
Discussion 4, 7: I would write "prevalence of F0-F1 stage fibrosis".
Table 2: add "in patients with excessive alcohol consumption".
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?
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: 
The Prevalence of Alcoholic and Nonalcoholic Fatty Liver Disease in
Adolescents and Young Adults in the United States: Analysis of the NHANES
Database
Version: 
0 
Date: 
08 Apr 2022
Reviewer's report:
GENERAL COMMENT
This is an interesting and generally well-written paper. I have the following
comments.
MAJOR COMMENTS
Outcome measures: The Authors are to be commended for using the NHANES
survey weights for analyzing the data. I have however the following question:
how can one be sure that these data are still representative of the general US
population after the "artificial" selection based on age and the other entry criteria
is taken into account?
Discussion 1, 56: reference 5 (which has no title, see below) excluded "pediatric
cohorts". You refer to the NHANES 2008 cycle, but the reference is a systematic
review excluding young subjects.
Discussion 2, 12: referring to a generic explanation given by overviews is not
useful.
Discussion 4, 18: please explain the choice of the 248dB/m cut-point. Give a
reference to published data or quote your unpublished experience with this cut-
point.
Discussion 4, 32: why do you consider your results as "preliminary"? With the
possible limitation of the missing representativeness (which I fear is
unavoidable, and I do not consider problematic if openly addressed), your results
do not seem "preliminary" to me.
Limitations: I would expect that NHANES has produced data about the intra-
and inter-rater agreement of CAP and LSM measurements. It has certainly done
that for most of the measurements available in its databases. Please provide such
data if they are available.
Limitations: NAFLD and AFLD are differentiated only by alcohol intake, and
this complicates a lot any inference about NAFLD and alcohol intake (not to
consider the measurement error of the instruments commonly employed to
measure alcohol intake). I think—and I am surely not alone—that the overall
evidence favors no consumption of alcohol in the presence of any liver disease.
Conclusion: "dire approach to the encumbrance": I would avoid such phrasing.
Moreover, in the general population such as that studied here, most cases of fatty
liver will not "progress" to liver fibrosis. Please consider this fact in the
discussion of your results. 
Figure 1: 
please provide separately the numbers obtained after excluding by age
and by the other criteria. It would be nice to have a supplementary table
comparing the general characteristics to those with available and missing VCTE.
The missingness of alcohol consumption data is very high. You should explain
why it is so and whether you think if it can be considered random. Again, a table
comparing the general characteristics of those with and those without alcohol
data would be useful.
References: some references are lacking the title. Please check all references
carefully.
MINOR COMMENTS
Short abstract: please give the operational definition of excessive alcohol
consumption.
Abstract 1,7 and elsewhere: the word "burden" is presently (mostly) used in a
very technical sense. I suggest not using it together with prevalence. Prevalence
is more than enough. Your message is clear.
Abstract and elsewhere: please use "suspected fibrosis" as you did with
"suspected NAFLD" and "suspected FLD".
Abstract and elsewhere: I propose replacing "to be at risk of…" with "have…".
This is, in fact, a cross-sectional study. (I admit the use or risk is presently very
lax).
Background: please provide references to support the use of VCTE for the
diagnosis of liver steatosis. Is it better than liver ultrasonography? Why?
Database: it would be nice to have a web link to the dataset employed for the
present analysis.
Definitions and inclusion criteria: please explain differences between ALQ130
and ALQ121.
Discussion 1, 54: graphs 4 and 5 should be figures 4 and 5.
Discussion 3, 35: I would write "no unique pattern of liver enzymes and other
markers" (e.g., MCV).
Discussion 3, 50: I would avoid using the adjective "tremendous" as it has no
scientific value.
Discussion 4, 7: I would write "prevalence of F0-F1 stage fibrosis".
Table 2: add "in patients with excessive alcohol consumption".
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?
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: 
The Prevalence of Alcoholic and Nonalcoholic Fatty Liver Disease in
Adolescents and Young Adults in the United States: Analysis of the NHANES
Database
Version: 
0 
Date: 
08 Apr 2022
Reviewer's report:
GENERAL COMMENT
This is an interesting and generally well-written paper. I have the following
comments.
MAJOR COMMENTS
Outcome measures: The Authors are to be commended for using the NHANES
survey weights for analyzing the data. I have however the following question:
how can one be sure that these data are still representative of the general US
population after the "artificial" selection based on age and the other entry criteria
is taken into account?
Discussion 1, 56: reference 5 (which has no title, see below) excluded "pediatric
cohorts". You refer to the NHANES 2008 cycle, but the reference is a systematic
review excluding young subjects.
Discussion 2, 12: referring to a generic explanation given by overviews is not
useful.
Discussion 4, 18: please explain the choice of the 248dB/m cut-point. Give a
reference to published data or quote your unpublished experience with this cut-
point.
Discussion 4, 32: why do you consider your results as "preliminary"? With the
possible limitation of the missing representativeness (which I fear is
unavoidable, and I do not consider problematic if openly addressed), your results
do not seem "preliminary" to me.
Limitations: I would expect that NHANES has produced data about the intra-
and inter-rater agreement of CAP and LSM measurements. It has certainly done
that for most of the measurements available in its databases. Please provide such
data if they are available.
Limitations: NAFLD and AFLD are differentiated only by alcohol intake, and
this complicates a lot any inference about NAFLD and alcohol intake (not to
consider the measurement error of the instruments commonly employed to
measure alcohol intake). I think—and I am surely not alone—that the overall
evidence favors no consumption of alcohol in the presence of any liver disease.
Conclusion: "dire approach to the encumbrance": I would avoid such phrasing.
Moreover, in the general population such as that studied here, most cases of fatty
liver will not "progress" to liver fibrosis. Please consider this fact in the
discussion of your results. 
Figure 1: 
please provide separately the numbers obtained after excluding by age
and by the other criteria. It would be nice to have a supplementary table
comparing the general characteristics to those with available and missing VCTE.
The missingness of alcohol consumption data is very high. You should explain
why it is so and whether you think if it can be considered random. Again, a table
comparing the general characteristics of those with and those without alcohol
data would be useful.
References: some references are lacking the title. Please check all references
carefully.
MINOR COMMENTS
Short abstract: please give the operational definition of excessive alcohol
consumption.
Abstract 1,7 and elsewhere: the word "burden" is presently (mostly) used in a
very technical sense. I suggest not using it together with prevalence. Prevalence
is more than enough. Your message is clear.
Abstract and elsewhere: please use "suspected fibrosis" as you did with
"suspected NAFLD" and "suspected FLD".
Abstract and elsewhere: I propose replacing "to be at risk of…" with "have…".
This is, in fact, a cross-sectional study. (I admit the use or risk is presently very
lax).
Background: please provide references to support the use of VCTE for the
diagnosis of liver steatosis. Is it better than liver ultrasonography? Why?
Database: it would be nice to have a web link to the dataset employed for the
present analysis.
Definitions and inclusion criteria: please explain differences between ALQ130
and ALQ121.
Discussion 1, 54: graphs 4 and 5 should be figures 4 and 5.
Discussion 3, 35: I would write "no unique pattern of liver enzymes and other
markers" (e.g., MCV).
Discussion 3, 50: I would avoid using the adjective "tremendous" as it has no
scientific value.
Discussion 4, 7: I would write "prevalence of F0-F1 stage fibrosis".
Table 2: add "in patients with excessive alcohol consumption".
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?
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