Title: The HbA1c/HDL-C Ratio as a Screening indicator of NAFLD in U.S. Adults:A Cross-
sectional NHANES Analysis (2017–2020)
Version: 1 Date: 31 Mar 2025
Reviewer's report:
Dear Editor,
Thank you for inviting me to review the manuscript entitled "Association Between the Plasma
Glycated Hemoglobin/High-Density Lipoprotein Cholesterol Ratio and NAFLD and Liver
Fibrosis Detected by Vibration-Controlled Transient Elastography in U.S. Adults: A Cross-
Sectional Analysis of NHANES 2017-2020."
This manuscript examines the association between the HbA1c/HDL-C ratio and the risk of
non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in U.S. adults, utilizing data
from the 2017–2020 NHANES cohort. The authors used logistic regression, restricted cubic
splines (RCS), and receiver operating characteristic (ROC) analysis to evaluate the predictive
performance of HbA1c/HDL-C for NAFLD and liver fibrosis. Findings indicate a significant
positive correlation between HbA1c/HDL-C and NAFLD, while no significant association was
observed for liver fibrosis.
Clinical Comments
Clarify Clinical Implications for Non-Diabetic Populations
The study highlights that HbA1c/HDL-C predicts NAFLD better in non-diabetic individuals.
However, clinical implications for non-diabetic patients remain unclear. Are there specific
thresholds or population-based screening protocols that should be considered in this subset?
The authors should clarify how these findings could translate into personalized NAFLD risk
stratification.
Address Implications of Non-Significant Association with Liver Fibrosis
While the manuscript reports no significant association between HbA1c/HDL-C and liver
fibrosis, potential explanations (e.g., sample size, fibrosis stage variability, or lack of sensitivity
in elastography) should be provided to guide future research directions.
Statistical Comments
Consider Sensitivity Analyses for Threshold Effects
The RCS analysis identifies an inflection point at 5.743 for HbA1c/HDL-C and NAFLD.
However, sensitivity analyses exploring alternate inflection points or subgroup-specific
thresholds would enhance robustness and generalizability of this cut-off.
Provide Details on Model Calibration
While ROC and AUC values are reported, model calibration metrics such as Brier scores or
calibration plots should be presented to assess model accuracy. This ensures that predictions
remain accurate across different HbA1c/HDL-C ranges.
Title: The HbA1c/HDL-C Ratio as a Screening indicator of NAFLD in U.S. Adults:A Cross-
sectional NHANES Analysis (2017–2020)
Version: 1 Date: 31 Mar 2025
Reviewer's report:
Dear Editor,
Thank you for inviting me to review the manuscript entitled "Association Between the Plasma
Glycated Hemoglobin/High-Density Lipoprotein Cholesterol Ratio and NAFLD and Liver
Fibrosis Detected by Vibration-Controlled Transient Elastography in U.S. Adults: A Cross-
Sectional Analysis of NHANES 2017-2020."
This manuscript examines the association between the HbA1c/HDL-C ratio and the risk of
non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in U.S. adults, utilizing data
from the 2017–2020 NHANES cohort. The authors used logistic regression, restricted cubic
splines (RCS), and receiver operating characteristic (ROC) analysis to evaluate the predictive
performance of HbA1c/HDL-C for NAFLD and liver fibrosis. Findings indicate a significant
positive correlation between HbA1c/HDL-C and NAFLD, while no significant association was
observed for liver fibrosis.
Clinical Comments
Clarify Clinical Implications for Non-Diabetic Populations
The study highlights that HbA1c/HDL-C predicts NAFLD better in non-diabetic individuals.
However, clinical implications for non-diabetic patients remain unclear. Are there specific
thresholds or population-based screening protocols that should be considered in this subset?
The authors should clarify how these findings could translate into personalized NAFLD risk
stratification.
Address Implications of Non-Significant Association with Liver Fibrosis
While the manuscript reports no significant association between HbA1c/HDL-C and liver
fibrosis, potential explanations (e.g., sample size, fibrosis stage variability, or lack of sensitivity
in elastography) should be provided to guide future research directions.
Statistical Comments
Consider Sensitivity Analyses for Threshold Effects
The RCS analysis identifies an inflection point at 5.743 for HbA1c/HDL-C and NAFLD.
However, sensitivity analyses exploring alternate inflection points or subgroup-specific
thresholds would enhance robustness and generalizability of this cut-off.
Provide Details on Model Calibration
While ROC and AUC values are reported, model calibration metrics such as Brier scores or
calibration plots should be presented to assess model accuracy. This ensures that predictions
remain accurate across different HbA1c/HDL-C ranges.
Please review this paper.
user
Title: The HbA1c/HDL-C Ratio as a Screening indicator of NAFLD in U.S. Adults:A Cross-
sectional NHANES Analysis (2017–2020)
Version: 1 Date: 31 Mar 2025
Reviewer's report:
Dear Editor,
Thank you for inviting me to review the manuscript entitled "Association Between the Plasma
Glycated Hemoglobin/High-Density Lipoprotein Cholesterol Ratio and NAFLD and Liver
Fibrosis Detected by Vibration-Controlled Transient Elastography in U.S. Adults: A Cross-
Sectional Analysis of NHANES 2017-2020."
This manuscript examines the association between the HbA1c/HDL-C ratio and the risk of
non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in U.S. adults, utilizing data
from the 2017–2020 NHANES cohort. The authors used logistic regression, restricted cubic
splines (RCS), and receiver operating characteristic (ROC) analysis to evaluate the predictive
performance of HbA1c/HDL-C for NAFLD and liver fibrosis. Findings indicate a significant
positive correlation between HbA1c/HDL-C and NAFLD, while no significant association was
observed for liver fibrosis.
Clinical Comments
Clarify Clinical Implications for Non-Diabetic Populations
The study highlights that HbA1c/HDL-C predicts NAFLD better in non-diabetic individuals.
However, clinical implications for non-diabetic patients remain unclear. Are there specific
thresholds or population-based screening protocols that should be considered in this subset?
The authors should clarify how these findings could translate into personalized NAFLD risk
stratification.
Address Implications of Non-Significant Association with Liver Fibrosis
While the manuscript reports no significant association between HbA1c/HDL-C and liver
fibrosis, potential explanations (e.g., sample size, fibrosis stage variability, or lack of sensitivity
in elastography) should be provided to guide future research directions.
Statistical Comments
Consider Sensitivity Analyses for Threshold Effects
The RCS analysis identifies an inflection point at 5.743 for HbA1c/HDL-C and NAFLD.
However, sensitivity analyses exploring alternate inflection points or subgroup-specific
thresholds would enhance robustness and generalizability of this cut-off.
Provide Details on Model Calibration
While ROC and AUC values are reported, model calibration metrics such as Brier scores or
calibration plots should be presented to assess model accuracy. This ensures that predictions
remain accurate across different HbA1c/HDL-C ranges.
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