Title: Population-specific cut-off points of fatty liver index: A study based on the National
Health and Nutrition Examination Survey data
Version: 1 Date: 14 Feb 2022
Reviewer's report:
GENERAL COMMENT
This is an interesting study aiming at identifying cut-points of the fatty liver index (FLI) for the
general US population.
MAJOR COMMENTS
1. Please, note that – to have data which are truly representative of the US population using
NHANES – one has to consider its complex multistage probability design:
https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/Overview.aspx?BeginYear=2015.
Together with the exclusion of most subjects from the analysis (see below), the analyzed data
are unlikely to be representative of the whole US population. You can simply recognize this
limitation without the need of considering the complex multistage probability design.
2. 78% of NHANES 2017-2018 and 62% of NHANES III subjects were evaluated. Note that
NHANES researchers suggest handling missing data by multiple imputation. I am not asking
you to do that. I recommend that you recognize the limitations of this approach. It would
also be nice to have a paragraph in the Discussion addressing the limitations of the study, as
is generally requested by any research journal. A supplementary figure giving the number of
excluded subjects with the reason for exclusion would greatly increase – in my opinion – the
value of this manuscript. Furthermore, what do you mean with “invalid data”?
3. I am not a fan of the Youden index as a means to evaluate the accuracy of a diagnostic test.
The reason is that it gives the same weight to sensitivity and specificity and offers just one cut-
point. A diagnostic test is used at different cut-points to separately increase its sensitivity and
specificity, and there will always be a “gray zone” where no clinical decision can be taken.
For instance, the FLI was developed using two cut-points – which of course may vary from
population to population – with the aim of having values to “rule in” and “rule out” hepatic
steatosis. I am not asking you to perform a new analysis, but simply to defend your choice of
the Youden index.
4. Please recognize that a direct comparison of LUTE vs. conventional ultrasonography is not
possible here because they were performed in different NHANES samples. It is of course nice
to find that FLI performs reasonably well with a reportedly more accurate technique than that
with which it was developed.
MINOR COMMENTS
There are several typing and spelling errors. The paper should be checked by a mother-tongue.
Please report 95% confidence intervals for point estimates of prevalence of MAFLD.
P4 L2 I would not say that LUTE is “inexpensive”.
P10 L1 What do you mean by “dietary”.
P10 L13 NHANES data are not census data. See major comment #1 above.
P4 Note that sex was *not* a predictor of fatty liver in the FLI study and this is the reason why
it was not taken into account. Race could not be taken into account simply because all subjects
were Italian (Caucasian).
Title: Population-specific cut-off points of fatty liver index: A study based on the National
Health and Nutrition Examination Survey data
Version: 1 Date: 14 Feb 2022
Reviewer's report:
GENERAL COMMENT
This is an interesting study aiming at identifying cut-points of the fatty liver index (FLI) for the
general US population.
MAJOR COMMENTS
1. Please, note that – to have data which are truly representative of the US population using
NHANES – one has to consider its complex multistage probability design:
https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/Overview.aspx?BeginYear=2015.
Together with the exclusion of most subjects from the analysis (see below), the analyzed data
are unlikely to be representative of the whole US population. You can simply recognize this
limitation without the need of considering the complex multistage probability design.
2. 78% of NHANES 2017-2018 and 62% of NHANES III subjects were evaluated. Note that
NHANES researchers suggest handling missing data by multiple imputation. I am not asking
you to do that. I recommend that you recognize the limitations of this approach. It would
also be nice to have a paragraph in the Discussion addressing the limitations of the study, as
is generally requested by any research journal. A supplementary figure giving the number of
excluded subjects with the reason for exclusion would greatly increase – in my opinion – the
value of this manuscript. Furthermore, what do you mean with “invalid data”?
3. I am not a fan of the Youden index as a means to evaluate the accuracy of a diagnostic test.
The reason is that it gives the same weight to sensitivity and specificity and offers just one cut-
point. A diagnostic test is used at different cut-points to separately increase its sensitivity and
specificity, and there will always be a “gray zone” where no clinical decision can be taken.
For instance, the FLI was developed using two cut-points – which of course may vary from
population to population – with the aim of having values to “rule in” and “rule out” hepatic
steatosis. I am not asking you to perform a new analysis, but simply to defend your choice of
the Youden index.
4. Please recognize that a direct comparison of LUTE vs. conventional ultrasonography is not
possible here because they were performed in different NHANES samples. It is of course nice
to find that FLI performs reasonably well with a reportedly more accurate technique than that
with which it was developed.
MINOR COMMENTS
There are several typing and spelling errors. The paper should be checked by a mother-tongue.
Please report 95% confidence intervals for point estimates of prevalence of MAFLD.
P4 L2 I would not say that LUTE is “inexpensive”.
P10 L1 What do you mean by “dietary”.
P10 L13 NHANES data are not census data. See major comment #1 above.
P4 Note that sex was *not* a predictor of fatty liver in the FLI study and this is the reason why
it was not taken into account. Race could not be taken into account simply because all subjects
were Italian (Caucasian).
Please review this paper.
user
Title: Population-specific cut-off points of fatty liver index: A study based on the National
Health and Nutrition Examination Survey data
Version: 1 Date: 14 Feb 2022
Reviewer's report:
GENERAL COMMENT
This is an interesting study aiming at identifying cut-points of the fatty liver index (FLI) for the
general US population.
MAJOR COMMENTS
1. Please, note that – to have data which are truly representative of the US population using
NHANES – one has to consider its complex multistage probability design:
https://wwwn.cdc.gov/nchs/nhanes/continuousnhanes/Overview.aspx?BeginYear=2015.
Together with the exclusion of most subjects from the analysis (see below), the analyzed data
are unlikely to be representative of the whole US population. You can simply recognize this
limitation without the need of considering the complex multistage probability design.
2. 78% of NHANES 2017-2018 and 62% of NHANES III subjects were evaluated. Note that
NHANES researchers suggest handling missing data by multiple imputation. I am not asking
you to do that. I recommend that you recognize the limitations of this approach. It would
also be nice to have a paragraph in the Discussion addressing the limitations of the study, as
is generally requested by any research journal. A supplementary figure giving the number of
excluded subjects with the reason for exclusion would greatly increase – in my opinion – the
value of this manuscript. Furthermore, what do you mean with “invalid data”?
3. I am not a fan of the Youden index as a means to evaluate the accuracy of a diagnostic test.
The reason is that it gives the same weight to sensitivity and specificity and offers just one cut-
point. A diagnostic test is used at different cut-points to separately increase its sensitivity and
specificity, and there will always be a “gray zone” where no clinical decision can be taken.
For instance, the FLI was developed using two cut-points – which of course may vary from
population to population – with the aim of having values to “rule in” and “rule out” hepatic
steatosis. I am not asking you to perform a new analysis, but simply to defend your choice of
the Youden index.
4. Please recognize that a direct comparison of LUTE vs. conventional ultrasonography is not
possible here because they were performed in different NHANES samples. It is of course nice
to find that FLI performs reasonably well with a reportedly more accurate technique than that
with which it was developed.
MINOR COMMENTS
There are several typing and spelling errors. The paper should be checked by a mother-tongue.
Please report 95% confidence intervals for point estimates of prevalence of MAFLD.
P4 L2 I would not say that LUTE is “inexpensive”.
P10 L1 What do you mean by “dietary”.
P10 L13 NHANES data are not census data. See major comment #1 above.
P4 Note that sex was *not* a predictor of fatty liver in the FLI study and this is the reason why
it was not taken into account. Race could not be taken into account simply because all subjects
were Italian (Caucasian).
assistant