Review for 10.1186/s12876-025-03831-0 (2025)

Title: The Fasting Plasma Glucose to High-Density Lipoprotein Cholesterol Ratio: A Novel
Index for Identifying NAFLD
Version: 0 Date: 06 Dec 2024
Reviewer:  Nam Nhat Nguyen
Reviewer's report:
This study evaluates the potential utility of the fasting plasma glucose (FPG) to high-density
lipoprotein cholesterol (HDL-C) ratio (FHR) as a novel, less invasive marker for non-alcoholic
fatty liver disease (NAFLD) compared to liver biopsy.
The study has several notable strengths, including a large sample size and efforts to adjust
for multiple variables. However, the authors acknowledge certain limitations, such as the
observational design restricting causal inference, participant recruitment from a single center
limiting generalizability, and the reliance on abdominal ultrasound for diagnosing NAFLD,
which may introduce misclassification bias.
While the study provides valuable insights, several areas require further discussion:
Major points:
1) Given that participants underwent physical examinations over a long period (1994–2016),
could temporal heterogeneity in diagnostic techniques, particularly advancements in ultrasound
technology, introduce technical bias?
2) Unlike more advanced tools such as MRI or VCTE-CAP, abdominal ultrasound provides
only qualitative findings (e.g., bright hepatic echoes, increased hepatorenal echogenicity, and
vascular blurring) rather than quantifying steatosis (e.g., liver fat content). This limitation may
lead to misclassification of NAFLD patients.
3) According to Figure 1 and the text, a total of 14,251 participants were included in the study.
However, Table 1 reports a total of 14,242 participants across the four FHR groups. Please
clarify this discrepancy.
4) Since FHR is the primary independent variable in this study, the Methods section should
include a detailed explanation of how FHR is calculated, including the units of measurement
for the numerator and denominator.
5) The term “quartile interval” is uncommon and lacks a standardized definition. It would be
more appropriate to use “interquartile range” to describe the difference between the third quartile
(Q3) and the first quartile (Q1).
6) Why were individuals with diabetes and impaired fasting glucose excluded from the study,
given that diabetes is a well-established risk factor for NAFLD?
7) he authors should provide additional details in the Methods about how the optimal thresholds
for each measure in the AUC plot were determined.
8) The text mentions that the p-value of the Delong test comparing AUCs between indices was
p < 0.05, while Table 4’s footnote indicates p < 0.001. This discrepancy needs clarification.
9) The claim that this study is the first to identify a correlation between FHR and NAFLD is
overstated. Similar findings have been reported, such as in the study by Jin et al. (Front Med,
2024).
10) The section labeled “Strengths” primarily discusses the novelty and applicability of the topic
rather than the study’s actual strengths. The strengths should focus on aspects such as the large
sample size and adjustment for multiple confounding variables.
Minor points: Many grammars in the text require some adjustments for clarity and correctness,
such as:
1) Lines 112-115: “Several progressively adjusted models were developed to analyze this
association: Model 1 age height, body mass index (BMI), and sex adjusted. Model 2 further
adjusted for SBP and lifestyle habits (such as exercise habits, drinking and smoking) in addition
to the variables in Model 1. Model 3 all non-collinear variables adjusted.”
2) Lines 128-129: dd the word “respectively” for better clarity.
3) Lines 131-132: “Additionally, the high FHR group exhibited higher levels of DBP, GGT,
HbA1c, weight, ALT, TG, WC, height, SBP, AST and BMI, than the low FHR group”. Use the
plural form for “groups” and reorder variables for coherence.
4) Table 2: add a comma between “sex” and “height” in the table footnote.
5) The authors should consistently use either “sex” or “gender” throughout the manuscript, not
both.