Review for 10.1186/s12876-025-03888-x (2025)

Title: Triglyceride glucose waist circumference and Non alcoholic fatty liver disease: a
systematic review and meta analysis
Version: 0 Date: 18 Feb 2025
Reviewer's report:
Dear Editor,
I would like to thank you for the opportunity to review the manuscript titled "Triglyceride
glucose waist circumference and Non-alcoholic fatty liver disease: a systematic review and
meta-analysis." This is an insightful and timely study that investigates the relationship between
the triglyceride glucose waist circumference (TyG-WC) index and non-alcoholic fatty liver
disease (NAFLD). Given the increasing burden of NAFLD globally, identifying reliable
predictors such as TyG-WC is crucial for early diagnosis and intervention.
After reviewing the manuscript thoroughly, I have provided several comments and suggestions
below that could strengthen the clarity and impact of the paper.
Clinical Comments:
Updated Prevalence of NAFLD: I recommend updating the introduction with the most recent
global prevalence of NAFLD, which is currently estimated to be 30.2%. This would provide
an updated context for the significance of your findings. Citing the recent paper DOI: 10.1016/
j.arcmed.2024.103043 would further strengthen this point.
Gut Microbiota and Metabolic Pathways: Given the increasing understanding of the role of gut
microbiota in liver diseases, I encourage the authors to briefly discuss how gut dysbiosis might
influence NAFLD development and progression, particularly through inflammatory pathways.
There is emerging evidence that gut microbiota plays a role in modulating insulin resistance and
liver fat accumulation, and adding this perspective could provide a more comprehensive view
of NAFLD. See the articles below, use their content and cite them.
doi.org/10.1038/s41387-024-00281-7
DOI: 10.1097/MS9.0000000000001740
doi.org/10.1016/j.clnesp.2023.07.087
doi: 10.3390/biomedicines10030550
doi.org/10.3389/fnut.2021.700058
Discussion on Mechanisms: While the manuscript explores the association between TyG-WC
and NAFLD risk, a more thorough explanation of the biological mechanisms underlying this
association would be beneficial. For instance, the role of visceral fat and its associated metabolic
disturbances in promoting liver fat deposition could be discussed in more detail.
Statistical Comments:
Sensitivity Analysis and Heterogeneity: The study reports high heterogeneity (I² = 96%) across
the studies. I recommend the authors explore the potential sources of heterogeneity in more
detail, such as differences in study populations, diagnostic criteria, and regional dietary factors.
Additionally, a sensitivity analysis based on study quality (e.g., cross-sectional vs. cohort
studies) could be valuable to better understand how study design affects the findings.
Nonlinear Relationships and Clinical Implications: The relationship between TyG-WC and
NAFLD risk appears nonlinear. The authors should clarify the clinical significance of the
identified cut-off points for TyG-WC levels. For example, at what TyG-WC score should
clinicians be particularly concerned about NAFLD risk, and how can these thresholds guide
preventive measures or clinical interventions?
Subgroup Analysis and Generalizability: The subgroup analysis is helpful, but I suggest that
the authors discuss the implications of their findings for different subgroups in more depth.
For instance, what do the results mean for populations in different regions or those with
comorbidities such as obesity or type 2 diabetes? This will help clinicians understand the broader
applicability of the TyG-WC index.