Review for 10.1186/s12876-025-03759-5 (2025)

Title: Estimated sdLDL-C as a biomarker of hepatic steatosis severity in MASLD: a
retrospective study
Version: 0 Date: 06 Feb 2025
Reviewer's report:
Dear Editor,
Thank you for the opportunity to review the manuscript titled "Relationship between estimated
small dense low-density lipoprotein cholesterol and severity of hepatic steatosis in patients
with NAFLD: a retrospective study." This study investigates the diagnostic role of estimated
small dense low-density lipoprotein cholesterol (EsdLDL-C) in assessing the severity of hepatic
steatosis in non-alcoholic fatty liver disease (NAFLD). The authors effectively demonstrate the
correlation between EsdLDL-C and the severity of hepatic steatosis in NAFLD patients, which
is a highly relevant topic considering the growing burden of NAFLD. The use of controlled
attenuation parameter (CAP) for assessing steatosis severity and the novel approach of using
EsdLDL-C as a diagnostic marker contribute to the value of the study.
Statistical Comments:
Clarification on Multivariate Analysis: The manuscript reports the results of logistic regression
analysis, but further clarification on the inclusion criteria for variables would enhance the
transparency of the methodology. How were variables chosen for inclusion in the model, and
were any potential confounders tested for multicollinearity before inclusion? Additionally, the
manuscript could benefit from more detailed interpretation of the odds ratios (OR) and their
clinical significance in the context of predicting severe steatosis.
ROC Curve and Cut-off Value: The authors present an ROC curve to evaluate the predictive
value of EsdLDL-C for identifying moderate-to-severe hepatic steatosis, with an AUC of 0.825.
While the results are promising, it would be useful to include a more in-depth discussion of
the clinical application of the proposed cut-off value (28.5 mg/dL). What are the potential
implications of using this threshold for screening and monitoring patients with NAFLD in
clinical practice? A comparison with existing biomarkers, such as ALT or FIB-4, would provide
better context.
Exploring Potential Bias in the Single-Center Design: The study design is retrospective and
single-center, which could limit the generalizability of the findings. While the sample size
is robust (461 patients), the authors should acknowledge this limitation and discuss whether
regional biases may influence the results. Additionally, any potential selection bias in patient
inclusion could be further addressed to strengthen the reliability of the conclusions.
Clinical Comments:
Clinical Relevance of EsdLDL-C: The manuscript's findings highlight that EsdLDL-C is an
independent predictor of the severity of hepatic steatosis in NAFLD patients. The clinical
relevance of these findings could be expanded. For instance, how might EsdLDL-C be integrated
into clinical practice to help identify patients who are at risk of progressing to more severe stages
of NAFLD? Could EsdLDL-C be used alongside other clinical markers (e.g., liver enzymes,
imaging techniques) to improve patient management and follow-up?
Impact of Lifestyle Factors: The study focuses on the biochemical and imaging markers of
NAFLD, but it would be valuable to discuss the role of lifestyle factors, such as diet and
physical activity, in the context of EsdLDL-C levels. Given that NAFLD is often associated
with metabolic syndrome, how might interventions targeting lifestyle changes (e.g., weight loss,
diet modification) impact EsdLDL-C levels and the progression of hepatic steatosis? A more
comprehensive view of patient management that includes lifestyle factors could enhance the
manuscript.
Validation of EsdLDL-C in Broader Populations: While the study demonstrates a significant
correlation between EsdLDL-C and steatosis severity in a Chinese cohort, the authors should
address the potential need for validation in other populations. How applicable are the findings
to diverse ethnic groups, and do different populations exhibit similar trends? The authors could
discuss the importance of validating EsdLDL-C as a predictive marker in diverse settings,
including Western cohorts or those with different metabolic profiles.
Updated Prevalence of NAFLD and Role of Gut Microbiota: The authors should update the
prevalence of non-alcoholic fatty liver disease (NAFLD) globally, as recent estimates suggest
that the prevalence has reached 30.2%. The authors are encouraged to cite the following study
for the updated prevalence:
DOI: 10.1016/j.arcmed.2024.103043
Furthermore, the manuscript would benefit from an expanded discussion on the role of
gut microbiota in the development and progression of NAFLD, particularly how microbiota
dysbiosis can influence lipid metabolism and liver health. The authors are encouraged to cite
the following studies, which provide valuable insights into the impact of gut microbiota on lipid
profiles in NAFLD patients:
DOI: 10.1093/nutrit/nuad086
DOI: 10.1016/j.arcmed.2024.103043
DOI: 10.1016/j.numecd.2024.05.017
DOI: 10.1186/s13643-023-02299-x
DOI: 10.1016/j.chom.2023.01.009
DOI: 10.1007/s11154-019-09512-0
These studies highlight how changes in gut microbiota composition can impact lipid profiles,
inflammation, and other metabolic pathways that contribute to the development and progression
of NAFLD. Including these references will enrich the manuscript by linking microbiota
dysbiosis to lipid metabolism in NAFLD, offering deeper insight into the potential therapeutic
avenues targeting the gut microbiota for managing this disease.