Review for 10.1186/s12876-025-03798-y (2025)

Title: A negative correlation of low estimated glucose disposal rate with significant liver fibrosis
in adults with NAFLD and obesity: results from NHANES 2017–2020
Version: 2 Date: 27 Feb 2025
Reviewer's report:
Dear Editor,
I would like to thank you for the opportunity to review the manuscript titled "A Negative
Correlation of Low Estimated Glucose Disposal Rate with Significant Liver Fibrosis in Adults
with NAFLD and Obesity: Results from NHANES 2017–2020." This is an insightful study that
highlights the relationship between the estimated glucose disposal rate (eGDR) and liver fibrosis
in individuals with non-alcoholic fatty liver disease (NAFLD) and obesity. The study's findings
contribute to a deeper understanding of the role of insulin resistance in liver fibrosis progression,
which is critical for better clinical management of NAFLD patients.
After reviewing the manuscript thoroughly, I have provided several comments and suggestions
that I believe could strengthen the manuscript.
Clinical Comments:
Updated Prevalence of NAFLD: I recommend that the authors update the introduction to include
the most recent meta-analysis on the global prevalence of NAFLD, which is now reported to be
30.2%. This would provide a more up-to-date context for the significance of the study's findings.
The authors could cite the following article to reflect this updated prevalence:
DOI: 10.1016/j.arcmed.2024.103043
Importance of Gut Microbiota: The manuscript discusses insulin resistance and liver fibrosis but
would benefit from a brief discussion on the role of gut microbiota in NAFLD and its potential
impact on liver fibrosis progression. Emerging evidence shows that gut dysbiosis can influence
metabolic pathways, inflammation, and fibrosis in NAFLD. I encourage the authors to consider
citing the following articles that explore the importance of gut microbiota in liver diseases:
DOI: 10.1016/j.clnesp.2023.07.087
DOI: 10.1038/s41387-024-00281-7
DOI: 10.2174/0115733998284844240102110559
DOI: 10.1038/s41467-020-18754-5
DOI: 10.1080/19490976.2023.2226922
Including this perspective will provide a broader understanding of how metabolic dysfunction
and gut health might collectively contribute to liver disease.
Mechanisms Linking eGDR and Liver Fibrosis: While the manuscript highlights the correlation
between eGDR and liver fibrosis, I encourage the authors to further elaborate on the biological
mechanisms linking eGDR, insulin resistance, and liver fibrosis. The role of visceral fat,
systemic inflammation, and gut-derived metabolic by-products could be explored in greater
depth to clarify how these factors contribute to fibrosis progression in NAFLD.
Statistical Comments:
Multivariate Model Adjustments: The authors adjust for several important covariates in their
multivariate logistic regression models. It would be helpful to discuss how potential confounders
like socioeconomic status, lifestyle factors (e.g., diet and exercise), and medication use were
incorporated into the analysis. These factors may have a significant influence on both eGDR
and liver fibrosis and could affect the results.
Sensitivity and Subgroup Analysis: The manuscript does well to explore the relationship
between eGDR and liver fibrosis in different BMI categories. However, I suggest the authors
perform additional stratified analyses by other key variables, such as age, sex, and the presence
of comorbidities (e.g., diabetes, hypertension), to further validate the findings and identify
subgroups that may benefit most from early fibrosis detection.
Clinical Applicability of eGDR Model: The authors developed a model incorporating eGDR,
BMI, age, AST, WBC, and PLT for fibrosis prediction. While this is a promising step, I
recommend that the authors explicitly discuss the clinical implications of this model. For
example, at what eGDR threshold should clinicians consider more aggressive monitoring or
interventions for NAFLD patients?