Title: METS-VF as a Novel Predictor of Gallstones in U.S. Adults: A Cross-Sectional Analysis
(NHANES 2017-2020)
Version: 0 Date: 21 Jun 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
1. Study Design Limitation (Cross-Sectional Nature)
The study is cross-sectional, yet the discussion sometimes implies causality between METS-VF
and gallstone formation.
Without longitudinal data, it is impossible to determine whether high METS-VF leads
to gallstones or whether pre-existing gallstones or other factors contribute to altered fat
metabolism.
Clearly emphasize the limitations in the abstract and discussion. Avoid language implying
causality (e.g., "intensifies the risk") and instead use more cautious phrasing like "is associated
with."
2. Definition and Validation of Gallstone Status
Gallstone status was identified via self-reported questionnaire data (i.e., whether participants
were told by a healthcare provider they had gallstones).
This introduces recall bias and lacks diagnostic validation (e.g., imaging).
Acknowledge the potential for misclassification bias and discuss how this could dilute or
exaggerate associations.
3. Lack of Gallstone Subtype Analysis
The study does not differentiate between types of gallstones (cholesterol vs. pigment) or
symptom status (asymptomatic vs. symptomatic).
Different types may have distinct pathophysiological pathways and associations with visceral
fat metabolism.
Discuss this limitation and, if possible, justify why subgroup data were unavailable or omitted.
4. No Adjustment for Dietary or Medication Confounders
Important lifestyle factors—such as dietary fat intake, fiber consumption, physical activity, and
use of lipid-lowering or hormone medications—were not adjusted for.
These are known risk modifiers for both visceral adiposity and gallstones, and their omission
could result in residual confounding.
Acknowledge the absence of these factors in the limitations section and their potential impact.
5. Overstated Superiority of METS-VF
The manuscript strongly emphasizes the superiority of METS-VF, yet AUC values for all obesity
indices were modest, and confidence intervals for ROC comparisons were not clearly shown.
The claim of METS-VF being “superior” may be overstated without a substantial difference in
predictive accuracy.
Include AUC values with confidence intervals in text/tables. Consider tempering the language
around METS-VF’s predictive utility.
6. Limited Discussion on Biological Plausibility
While mechanisms linking visceral fat to gallstones are mentioned, they are not deeply integrated
into the METS-VF construct.
Readers may question how well METS-VF captures the inflammatory or hormonal changes that
directly influence gallstone formation.
Strengthen the biological plausibility by explicitly linking METS-VF components (e.g., WHtR,
TG, HDL-C) to gallstone pathogenesis.
7. Lack of Clarity on XGBoost Use
The manuscript mentions the use of XGBoost but provides limited methodological detail or
justification for its use in this context.
The value of this analysis is unclear without performance metrics or comparison to logistic
regression results.
Clarify the purpose of XGBoost in the analysis (e.g., feature importance vs. classification) and
report relevant performance metrics (e.g., accuracy, precision, recall, AUC).
8. Overcomplexity in Methods Description
The methods section is somewhat overloaded with technical terms and formula references (e.g.,
METS-VF formula not shown, variable coding explanation embedded in narrative).
This may make reproducibility and understanding difficult for general readers.
Use supplementary materials to present complex equations and data derivation steps. Simplify
in-text explanations.
9. No Power Calculation or Justification of Sample Size
The manuscript does not present a power analysis or justify whether the sample size (n = 3,010)
was adequate to detect meaningful differences.
This raises concerns about the statistical power, especially for subgroup analyses.
Provide a brief sample size or power estimation in the Methods or Limitations section.
10. Inconsistent Use of Abbreviations
Some abbreviations (e.g., PIR, WHtR, METS-IR) are used without immediate definition in the
first instance.
This may impede readability for non-specialist readers.
Ensure all abbreviations are defined at first use and listed in a glossary or footnote.
Title: METS-VF as a Novel Predictor of Gallstones in U.S. Adults: A Cross-Sectional Analysis
(NHANES 2017-2020)
Version: 0 Date: 21 Jun 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
1. Study Design Limitation (Cross-Sectional Nature)
The study is cross-sectional, yet the discussion sometimes implies causality between METS-VF
and gallstone formation.
Without longitudinal data, it is impossible to determine whether high METS-VF leads
to gallstones or whether pre-existing gallstones or other factors contribute to altered fat
metabolism.
Clearly emphasize the limitations in the abstract and discussion. Avoid language implying
causality (e.g., "intensifies the risk") and instead use more cautious phrasing like "is associated
with."
2. Definition and Validation of Gallstone Status
Gallstone status was identified via self-reported questionnaire data (i.e., whether participants
were told by a healthcare provider they had gallstones).
This introduces recall bias and lacks diagnostic validation (e.g., imaging).
Acknowledge the potential for misclassification bias and discuss how this could dilute or
exaggerate associations.
3. Lack of Gallstone Subtype Analysis
The study does not differentiate between types of gallstones (cholesterol vs. pigment) or
symptom status (asymptomatic vs. symptomatic).
Different types may have distinct pathophysiological pathways and associations with visceral
fat metabolism.
Discuss this limitation and, if possible, justify why subgroup data were unavailable or omitted.
4. No Adjustment for Dietary or Medication Confounders
Important lifestyle factors—such as dietary fat intake, fiber consumption, physical activity, and
use of lipid-lowering or hormone medications—were not adjusted for.
These are known risk modifiers for both visceral adiposity and gallstones, and their omission
could result in residual confounding.
Acknowledge the absence of these factors in the limitations section and their potential impact.
5. Overstated Superiority of METS-VF
The manuscript strongly emphasizes the superiority of METS-VF, yet AUC values for all obesity
indices were modest, and confidence intervals for ROC comparisons were not clearly shown.
The claim of METS-VF being “superior” may be overstated without a substantial difference in
predictive accuracy.
Include AUC values with confidence intervals in text/tables. Consider tempering the language
around METS-VF’s predictive utility.
6. Limited Discussion on Biological Plausibility
While mechanisms linking visceral fat to gallstones are mentioned, they are not deeply integrated
into the METS-VF construct.
Readers may question how well METS-VF captures the inflammatory or hormonal changes that
directly influence gallstone formation.
Strengthen the biological plausibility by explicitly linking METS-VF components (e.g., WHtR,
TG, HDL-C) to gallstone pathogenesis.
7. Lack of Clarity on XGBoost Use
The manuscript mentions the use of XGBoost but provides limited methodological detail or
justification for its use in this context.
The value of this analysis is unclear without performance metrics or comparison to logistic
regression results.
Clarify the purpose of XGBoost in the analysis (e.g., feature importance vs. classification) and
report relevant performance metrics (e.g., accuracy, precision, recall, AUC).
8. Overcomplexity in Methods Description
The methods section is somewhat overloaded with technical terms and formula references (e.g.,
METS-VF formula not shown, variable coding explanation embedded in narrative).
This may make reproducibility and understanding difficult for general readers.
Use supplementary materials to present complex equations and data derivation steps. Simplify
in-text explanations.
9. No Power Calculation or Justification of Sample Size
The manuscript does not present a power analysis or justify whether the sample size (n = 3,010)
was adequate to detect meaningful differences.
This raises concerns about the statistical power, especially for subgroup analyses.
Provide a brief sample size or power estimation in the Methods or Limitations section.
10. Inconsistent Use of Abbreviations
Some abbreviations (e.g., PIR, WHtR, METS-IR) are used without immediate definition in the
first instance.
This may impede readability for non-specialist readers.
Ensure all abbreviations are defined at first use and listed in a glossary or footnote.
Please review this paper.
user
Title: METS-VF as a Novel Predictor of Gallstones in U.S. Adults: A Cross-Sectional Analysis
(NHANES 2017-2020)
Version: 0 Date: 21 Jun 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
1. Study Design Limitation (Cross-Sectional Nature)
The study is cross-sectional, yet the discussion sometimes implies causality between METS-VF
and gallstone formation.
Without longitudinal data, it is impossible to determine whether high METS-VF leads
to gallstones or whether pre-existing gallstones or other factors contribute to altered fat
metabolism.
Clearly emphasize the limitations in the abstract and discussion. Avoid language implying
causality (e.g., "intensifies the risk") and instead use more cautious phrasing like "is associated
with."
2. Definition and Validation of Gallstone Status
Gallstone status was identified via self-reported questionnaire data (i.e., whether participants
were told by a healthcare provider they had gallstones).
This introduces recall bias and lacks diagnostic validation (e.g., imaging).
Acknowledge the potential for misclassification bias and discuss how this could dilute or
exaggerate associations.
3. Lack of Gallstone Subtype Analysis
The study does not differentiate between types of gallstones (cholesterol vs. pigment) or
symptom status (asymptomatic vs. symptomatic).
Different types may have distinct pathophysiological pathways and associations with visceral
fat metabolism.
Discuss this limitation and, if possible, justify why subgroup data were unavailable or omitted.
4. No Adjustment for Dietary or Medication Confounders
Important lifestyle factors—such as dietary fat intake, fiber consumption, physical activity, and
use of lipid-lowering or hormone medications—were not adjusted for.
These are known risk modifiers for both visceral adiposity and gallstones, and their omission
could result in residual confounding.
Acknowledge the absence of these factors in the limitations section and their potential impact.
5. Overstated Superiority of METS-VF
The manuscript strongly emphasizes the superiority of METS-VF, yet AUC values for all obesity
indices were modest, and confidence intervals for ROC comparisons were not clearly shown.
The claim of METS-VF being “superior” may be overstated without a substantial difference in
predictive accuracy.
Include AUC values with confidence intervals in text/tables. Consider tempering the language
around METS-VF’s predictive utility.
6. Limited Discussion on Biological Plausibility
While mechanisms linking visceral fat to gallstones are mentioned, they are not deeply integrated
into the METS-VF construct.
Readers may question how well METS-VF captures the inflammatory or hormonal changes that
directly influence gallstone formation.
Strengthen the biological plausibility by explicitly linking METS-VF components (e.g., WHtR,
TG, HDL-C) to gallstone pathogenesis.
7. Lack of Clarity on XGBoost Use
The manuscript mentions the use of XGBoost but provides limited methodological detail or
justification for its use in this context.
The value of this analysis is unclear without performance metrics or comparison to logistic
regression results.
Clarify the purpose of XGBoost in the analysis (e.g., feature importance vs. classification) and
report relevant performance metrics (e.g., accuracy, precision, recall, AUC).
8. Overcomplexity in Methods Description
The methods section is somewhat overloaded with technical terms and formula references (e.g.,
METS-VF formula not shown, variable coding explanation embedded in narrative).
This may make reproducibility and understanding difficult for general readers.
Use supplementary materials to present complex equations and data derivation steps. Simplify
in-text explanations.
9. No Power Calculation or Justification of Sample Size
The manuscript does not present a power analysis or justify whether the sample size (n = 3,010)
was adequate to detect meaningful differences.
This raises concerns about the statistical power, especially for subgroup analyses.
Provide a brief sample size or power estimation in the Methods or Limitations section.
10. Inconsistent Use of Abbreviations
Some abbreviations (e.g., PIR, WHtR, METS-IR) are used without immediate definition in the
first instance.
This may impede readability for non-specialist readers.
Ensure all abbreviations are defined at first use and listed in a glossary or footnote.
assistant