Review for 10.1186/s12876-025-03974-0 (2025)

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: 29 Mar 2025
Reviewer:  Amira A. A. Othman
Reviewer's report:
First of all
I want to congratulate the authors on their work. In this study, Wu et al. aimed to investigate
the association between the glycated hemoglobin/high-density lipoprotein cholesterol (GHR)
ratio and the presence of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in U.S.
adults. By using data from NHANES and assessing liver status via vibration-controlled transient
elastography (VCTE), the study seeks to determine whether GHR can serve as a reliable
biomarker for identifying individuals at higher risk for NAFLD and fibrosis.
Non-alcoholic fatty liver disease (NAFLD) is recognized as the most prevalent chronic liver
disease, impacting about 30% of global individuals, with the potential to progress to advanced
hepatic fibrosis and end-stage liver diseases eventually [*]. In June 2023, a multi-society
committee of international experts was gathered, and new terminology was adopted to reduce
stigma and increase disease awareness [**]. A new terminology, Steatotic liver disease (SLD),
replaces “fatty liver disease” as the umbrella term. Under subgroups of SLD, NAFLD has been
renamed as metabolic dysfunction-associated Steatotic liver disease (MASLD) [**]. NAFLD/
MASLD is closely related to metabolic syndrome (MetS) and its associated components of
hypertension, type 2 diabetes mellitus, dyslipidemia, and obesity[***].
(*:doi: 10.1097/HEP.0000000000000004, **: doi: 10.1016/j.jhep.2023.06.003, ***  doi:
10.1111/apt.17308).
The authors handled the reviewer comments satisfactorily, nevertheless, there is an observation
for which sufficient justification must be obtained.
In general:
1. The language is generally clear, but some minor grammatical errors and awkward phrasings
could be improved. Consider having the manuscript proofread by a native English speaker or
a professional editing service.
2. Abbreviations must be fully written at their first appearance.
In Title:
1. The current title is long and complex, making it difficult to read.
2. Make the title more specific by including the main variable, study type, or key finding. I
suggest “The Glycated Hemoglobin/HDL Ratio as a Predictor of MAFLD and Liver Fibrosis in
U.S. Adults: Evidence from NHANES 2017-2020”.
In the Abstract section
3. The background subsection in the abstract :
-  Should be the shortest part of the abstract. It should briefly outline the following information:
What is already known about the subject, related to the paper in question. What is not known
about the subject, and hence what the study intended to examine (or what the paper seeks to
present)? Please reconstruct it properly.
4.  The type of study: a population-based study.
5. In the method subsection in the abstract :
- It would help if you described the aim of your statistical analysis.
- Clarify study design and analysis techniques: “This cross-sectional study analyzed NHANES
data (2017–2020) using weighted logistic regression, etc.”
6. In the results subsection in the abstract :
- Include key numerical findings in the results section.
-  Clearly state how GHR was analyzed and categorized.
7. In the conclusion subsection in the abstract :
- Strengthen the conclusion by specifying how GHR could be used in clinical practice.
In the Introduction section:
8. Try to provide a summarized description of the National Health and Nutrition Examination
Survey (NHANES) in the background section. You may use the following: “NHANES
(www.cdc.gov/nchs/nhanes) is designed to assess the health and nutritional status of adults
and children in the United States. The survey is distinctive in that it incorporates both
physical examinations and interviews. Several cross-sectional, nationally representative health
examination surveys are part of the NHANES program. Questions about demographics,
health insurance status, dietary habits, acute and chronic medical issues, mental health, and
prescription drug use are all included in the health interview. Exam components can change
between survey cycles but typically include blood pressure, dental exams, vision, hearing,
dermatology, fitness, balance and strength testing, respiratory testing, taste and smell, and
body measurements (weight, height, skin folds, body composition scans). Hematology, organ
and endocrine function (e.g., thyroid, kidney), environmental exposure, dietary biomarkers,
metabolic and cardiovascular health, and infectious disease are a few examples of laboratory
components.
9. MAFLD must replace NAFLD:
“In contrast to NAFLD, MAFLD does not necessitate ruling out other liver disease causes, such
as viral hepatitis or heavy alcohol use*. The new name chosen to replace NAFLD reflected the
disease etiology better and conveyed a more practical approach in daily clinical practice than
NAFLD, considering its close association with metabolic syndrome**. Please discuss the new
nomenclature in more detail.
(*: Doi: 10.1016/j.jhep.2020.03.039, **: doi: 10.1097/HEP.0000000000000520).
10. Expand on why GHR is a relevant biomarker and how it compares to existing markers.
11.  Clearly state the research gap and justify why this study is necessary.
12. Add recent references to strengthen the background.
13. End the introduction with a clear research question or hypothesis.
In the Methods section:
14. Please move the sentences defining the NHANES to the introduction section rather than the
methodology section.
15. The study utilized the 2017-2020 NHANES survey cycle. Why did you choose the study
survey cycle? The survey includes study cycles from 2001 to 2023.
16. Please provide the participants' sociodemographic data.
17.  Provide more details on inclusion/exclusion criteria.
18.  Explain how confounders were handled in the statistical analysis. Clarify the thresholds
used for defining MAFLD and fibrosis.
In the Results section:
19. In all tables, please explain the abbreviations in tables.
20. You can title the statistical test column as “Test of significance” and use U= for the Mann–
Whitney U test, T= for the T-test, and #2 = for the Chi-square test, etc.. Although the Chi-square
test was used to compare observed and expected results, nothing was mentioned in the statistical
analysis section.
21. Ensure that table captions succinctly describe the content for standalone clarity.
22. Make key findings stand out more clearly.
23. Ensure tables and figures are labeled properly.
In the Discussion section:
24. The discussion section is one of the final parts of a research paper, in which an author
describes, analyzes, and interprets their findings. They explain the significance of those results
and tie everything back to the research question(s). In this manuscript, there is confusion
between what should be written in the introduction and discussion sections. Please reconstruct
the discussion section.
25. Add a discussion of the study’s limitations.
26. Critically analyze how these findings compare to previous studies.
27. Cite recent literature to strengthen your argument.
In the Conclusion section:
28. "Make the conclusion more specific; summarize the key findings without overgeneralizing.
29. Avoid speculation and suggest future research areas if relevant.
30. Briefly mention how GHR could be applied in clinical settings.