Title: MAFLD Mediates the Association Between CHR and Gallstones in the U.S. Adults:
Evidence from NHANES 2021-2023
Version: 1 Date: 28 Jan 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While self-reported diagnosis of gallstones is a common approach in large-scale
epidemiological surveys, it is susceptible to recall bias and misclassification. Acknowledging
these limitations in the methods section would improve transparency and strengthen the study's
reliability. If any measures were taken to validate self-reports (e.g., through medical records),
this would be worth noting.
-The definition of NAFLD based on liver ultrasound transient elastography and a controlled
attenuation parameter (CAP) score is valid, but further explanation could be provided regarding
the threshold used to classify NAFLD. Additionally, it would be useful to note how the CAP
score correlates with histological diagnoses of NAFLD, as this can affect the generalizability
of the findings.
-The confounders considered are extensive, but it would be beneficial to briefly mention any
possible interactions between these factors and CHR, NAFLD, or gallstones. For example, the
interaction between BMI and CHR might be of particular interest, as obesity is a known risk
factor for both NAFLD and gallstones.
-The study investigates important relationships, but the methods section could elaborate on how
the findings may translate into clinical practice. For instance, how might interventions aimed at
modulating CHR or managing NAFLD impact gallstone formation? Providing a brief discussion
of clinical implications would make the study’s potential impact clearer.
-Although the study controlled for numerous confounding variables, the discussion could
be more transparent about which potential confounders were not accounted for or might
still introduce bias. For example, factors like dietary habits, physical activity, and genetic
predisposition could influence gallstone risk but were not mentioned as potential confounders
in the study.
-The limitation regarding the self-reported diagnosis of gallstones is acknowledged, but the
discussion could explore the potential consequences of this more deeply. Specifically, the impact
of recall bias on the study's results and the possibility that some cases of gallstones may have
been undiagnosed or misclassified could influence the findings. A more thorough explanation
of how this might affect the reliability of the results could enhance the transparency of the study.
-While the mechanisms by which NAFLD may contribute to gallstone formation are discussed,
the explanation could be expanded. For example, more detail on the role of hepatic inflammation,
fibrosis, or the gut-liver axis could provide a fuller picture of how NAFLD might mediate the
CHR-gallstone relationship. Additionally, highlighting whether these mechanisms have been
observed in human studies or are based on animal models would add clarity.
Title: MAFLD Mediates the Association Between CHR and Gallstones in the U.S. Adults:
Evidence from NHANES 2021-2023
Version: 1 Date: 28 Jan 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While self-reported diagnosis of gallstones is a common approach in large-scale
epidemiological surveys, it is susceptible to recall bias and misclassification. Acknowledging
these limitations in the methods section would improve transparency and strengthen the study's
reliability. If any measures were taken to validate self-reports (e.g., through medical records),
this would be worth noting.
-The definition of NAFLD based on liver ultrasound transient elastography and a controlled
attenuation parameter (CAP) score is valid, but further explanation could be provided regarding
the threshold used to classify NAFLD. Additionally, it would be useful to note how the CAP
score correlates with histological diagnoses of NAFLD, as this can affect the generalizability
of the findings.
-The confounders considered are extensive, but it would be beneficial to briefly mention any
possible interactions between these factors and CHR, NAFLD, or gallstones. For example, the
interaction between BMI and CHR might be of particular interest, as obesity is a known risk
factor for both NAFLD and gallstones.
-The study investigates important relationships, but the methods section could elaborate on how
the findings may translate into clinical practice. For instance, how might interventions aimed at
modulating CHR or managing NAFLD impact gallstone formation? Providing a brief discussion
of clinical implications would make the study’s potential impact clearer.
-Although the study controlled for numerous confounding variables, the discussion could
be more transparent about which potential confounders were not accounted for or might
still introduce bias. For example, factors like dietary habits, physical activity, and genetic
predisposition could influence gallstone risk but were not mentioned as potential confounders
in the study.
-The limitation regarding the self-reported diagnosis of gallstones is acknowledged, but the
discussion could explore the potential consequences of this more deeply. Specifically, the impact
of recall bias on the study's results and the possibility that some cases of gallstones may have
been undiagnosed or misclassified could influence the findings. A more thorough explanation
of how this might affect the reliability of the results could enhance the transparency of the study.
-While the mechanisms by which NAFLD may contribute to gallstone formation are discussed,
the explanation could be expanded. For example, more detail on the role of hepatic inflammation,
fibrosis, or the gut-liver axis could provide a fuller picture of how NAFLD might mediate the
CHR-gallstone relationship. Additionally, highlighting whether these mechanisms have been
observed in human studies or are based on animal models would add clarity.
Please review this paper.
user
Title: MAFLD Mediates the Association Between CHR and Gallstones in the U.S. Adults:
Evidence from NHANES 2021-2023
Version: 1 Date: 28 Jan 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While self-reported diagnosis of gallstones is a common approach in large-scale
epidemiological surveys, it is susceptible to recall bias and misclassification. Acknowledging
these limitations in the methods section would improve transparency and strengthen the study's
reliability. If any measures were taken to validate self-reports (e.g., through medical records),
this would be worth noting.
-The definition of NAFLD based on liver ultrasound transient elastography and a controlled
attenuation parameter (CAP) score is valid, but further explanation could be provided regarding
the threshold used to classify NAFLD. Additionally, it would be useful to note how the CAP
score correlates with histological diagnoses of NAFLD, as this can affect the generalizability
of the findings.
-The confounders considered are extensive, but it would be beneficial to briefly mention any
possible interactions between these factors and CHR, NAFLD, or gallstones. For example, the
interaction between BMI and CHR might be of particular interest, as obesity is a known risk
factor for both NAFLD and gallstones.
-The study investigates important relationships, but the methods section could elaborate on how
the findings may translate into clinical practice. For instance, how might interventions aimed at
modulating CHR or managing NAFLD impact gallstone formation? Providing a brief discussion
of clinical implications would make the study’s potential impact clearer.
-Although the study controlled for numerous confounding variables, the discussion could
be more transparent about which potential confounders were not accounted for or might
still introduce bias. For example, factors like dietary habits, physical activity, and genetic
predisposition could influence gallstone risk but were not mentioned as potential confounders
in the study.
-The limitation regarding the self-reported diagnosis of gallstones is acknowledged, but the
discussion could explore the potential consequences of this more deeply. Specifically, the impact
of recall bias on the study's results and the possibility that some cases of gallstones may have
been undiagnosed or misclassified could influence the findings. A more thorough explanation
of how this might affect the reliability of the results could enhance the transparency of the study.
-While the mechanisms by which NAFLD may contribute to gallstone formation are discussed,
the explanation could be expanded. For example, more detail on the role of hepatic inflammation,
fibrosis, or the gut-liver axis could provide a fuller picture of how NAFLD might mediate the
CHR-gallstone relationship. Additionally, highlighting whether these mechanisms have been
observed in human studies or are based on animal models would add clarity.
assistant