Title: The Newly Proposed Plasma-Glycosylated Hemoglobin A1c/High-Density Lipoprotein
Cholesterol Ratio Serves as A Simple and Practical Indicator for Screening Metabolic
Associated Fatty Liver Disease: An Observational Study Based on A Physical Examination
Population
Version: 0 Date: 25 Jun 2024
Reviewer's report:
In the article titled “The Newly Proposed Plasma-Glycosylated Hemoglobin A1c/High-Density
Lipoprotein Cholesterol Ratio Serves as A Simple and Practical Indicator for Assessing Non-
alcoholic Fatty Liver Disease: An Observational Study Based on A Physical Examination
Population”, the authors have studied the association between the HbA1c/HDL-C ratio and
NAFLD in 14,251 individuals. The authors found a significant positive association between the
HbA1c/HDL-C ratio. The manuscript is well constructed, and the statistical analyses support
the conclusion. Still, I have concerns regarding the clinical utility of the findings. As the field is
moving from a diagnosis of exclusion (NAFLD) to an inclusive diagnosis of MAFLD, using of
a single parameter for the diagnosis or screening is counterintuitive.
Major comments
1. Title: “Indicator for Assessing Non-alcoholic Fatty Liver Disease” is a vague term. Are the
authors proposing HbA1c/HDL-C ratio for the diagnosis of NAFLD or is it a screening marker.
This needs to be clarified in the title and the manuscript.
2. Lines 240-242: Recommendations for HbA1c/HDL-C ratio cut-offs for the prevention of
NAFLD in general population are beyond the scope of this study. Such recommendations
would require longitudinal studies. Authors should refrain from making such arbitrary cut-offs.
Optimum cut-off values obtained from ROC analyses are not cut-offs for prevention in general
population.
3. Figure 3: The authors have shown that HbA1c/HDL-C ratio performs better than HbA1c or
HDL-C alone in ROC analysis. What about other predictors of MAFLD like WC, BP, and TG?
Does adding HbA1c/HDL-C ratio to WC, BP, or TG improve the AUC of these parameters?
This analysis would help in understanding the incremental value of HbA1c/HDL-C ratio over
these parameters.
Minor comments
1. Table 2: Table 2 analyses are repetitive. HbA1C/HDL-C ratio is a continuous variable and
authors have shown that it is significantly associated with NAFLD using logistic regression.
Dividing HbA1C/HDL-C into quartiles and quantifying the OR does not provide any additional
information.
2. Table 3: Abbreviations are incorrectly shown as FPG/HDL-C ratio.
3. Discussion section has repetitions of results. E.g., lines 221, 223, 239-240. These can be
removed.
Title: The Newly Proposed Plasma-Glycosylated Hemoglobin A1c/High-Density Lipoprotein
Cholesterol Ratio Serves as A Simple and Practical Indicator for Screening Metabolic
Associated Fatty Liver Disease: An Observational Study Based on A Physical Examination
Population
Version: 0 Date: 25 Jun 2024
Reviewer's report:
In the article titled “The Newly Proposed Plasma-Glycosylated Hemoglobin A1c/High-Density
Lipoprotein Cholesterol Ratio Serves as A Simple and Practical Indicator for Assessing Non-
alcoholic Fatty Liver Disease: An Observational Study Based on A Physical Examination
Population”, the authors have studied the association between the HbA1c/HDL-C ratio and
NAFLD in 14,251 individuals. The authors found a significant positive association between the
HbA1c/HDL-C ratio. The manuscript is well constructed, and the statistical analyses support
the conclusion. Still, I have concerns regarding the clinical utility of the findings. As the field is
moving from a diagnosis of exclusion (NAFLD) to an inclusive diagnosis of MAFLD, using of
a single parameter for the diagnosis or screening is counterintuitive.
Major comments
1. Title: “Indicator for Assessing Non-alcoholic Fatty Liver Disease” is a vague term. Are the
authors proposing HbA1c/HDL-C ratio for the diagnosis of NAFLD or is it a screening marker.
This needs to be clarified in the title and the manuscript.
2. Lines 240-242: Recommendations for HbA1c/HDL-C ratio cut-offs for the prevention of
NAFLD in general population are beyond the scope of this study. Such recommendations
would require longitudinal studies. Authors should refrain from making such arbitrary cut-offs.
Optimum cut-off values obtained from ROC analyses are not cut-offs for prevention in general
population.
3. Figure 3: The authors have shown that HbA1c/HDL-C ratio performs better than HbA1c or
HDL-C alone in ROC analysis. What about other predictors of MAFLD like WC, BP, and TG?
Does adding HbA1c/HDL-C ratio to WC, BP, or TG improve the AUC of these parameters?
This analysis would help in understanding the incremental value of HbA1c/HDL-C ratio over
these parameters.
Minor comments
1. Table 2: Table 2 analyses are repetitive. HbA1C/HDL-C ratio is a continuous variable and
authors have shown that it is significantly associated with NAFLD using logistic regression.
Dividing HbA1C/HDL-C into quartiles and quantifying the OR does not provide any additional
information.
2. Table 3: Abbreviations are incorrectly shown as FPG/HDL-C ratio.
3. Discussion section has repetitions of results. E.g., lines 221, 223, 239-240. These can be
removed.
Please review this paper.
user
Title: The Newly Proposed Plasma-Glycosylated Hemoglobin A1c/High-Density Lipoprotein
Cholesterol Ratio Serves as A Simple and Practical Indicator for Screening Metabolic
Associated Fatty Liver Disease: An Observational Study Based on A Physical Examination
Population
Version: 0 Date: 25 Jun 2024
Reviewer's report:
In the article titled “The Newly Proposed Plasma-Glycosylated Hemoglobin A1c/High-Density
Lipoprotein Cholesterol Ratio Serves as A Simple and Practical Indicator for Assessing Non-
alcoholic Fatty Liver Disease: An Observational Study Based on A Physical Examination
Population”, the authors have studied the association between the HbA1c/HDL-C ratio and
NAFLD in 14,251 individuals. The authors found a significant positive association between the
HbA1c/HDL-C ratio. The manuscript is well constructed, and the statistical analyses support
the conclusion. Still, I have concerns regarding the clinical utility of the findings. As the field is
moving from a diagnosis of exclusion (NAFLD) to an inclusive diagnosis of MAFLD, using of
a single parameter for the diagnosis or screening is counterintuitive.
Major comments
1. Title: “Indicator for Assessing Non-alcoholic Fatty Liver Disease” is a vague term. Are the
authors proposing HbA1c/HDL-C ratio for the diagnosis of NAFLD or is it a screening marker.
This needs to be clarified in the title and the manuscript.
2. Lines 240-242: Recommendations for HbA1c/HDL-C ratio cut-offs for the prevention of
NAFLD in general population are beyond the scope of this study. Such recommendations
would require longitudinal studies. Authors should refrain from making such arbitrary cut-offs.
Optimum cut-off values obtained from ROC analyses are not cut-offs for prevention in general
population.
3. Figure 3: The authors have shown that HbA1c/HDL-C ratio performs better than HbA1c or
HDL-C alone in ROC analysis. What about other predictors of MAFLD like WC, BP, and TG?
Does adding HbA1c/HDL-C ratio to WC, BP, or TG improve the AUC of these parameters?
This analysis would help in understanding the incremental value of HbA1c/HDL-C ratio over
these parameters.
Minor comments
1. Table 2: Table 2 analyses are repetitive. HbA1C/HDL-C ratio is a continuous variable and
authors have shown that it is significantly associated with NAFLD using logistic regression.
Dividing HbA1C/HDL-C into quartiles and quantifying the OR does not provide any additional
information.
2. Table 3: Abbreviations are incorrectly shown as FPG/HDL-C ratio.
3. Discussion section has repetitions of results. E.g., lines 221, 223, 239-240. These can be
removed.
assistant