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: 03 Mar 2025
Reviewer's report:
Dear authors,
The authors conduct a systematic review and meta-analysis (SRMA) to examine the
association between non-alcoholic fatty liver disease (NAFLD) and the triglyceride glucose-
waist circumference (TyG-WC) index by a systematic review and meta-analysis. A significant
mean difference (MD) in TyG-WC levels between NAFLD and non-NAFLD cases was found
in the study analysis, which suggests that the TyG-WC index, a novel measure for evaluating
insulin resistance (IR), may function as a potential indicator for NAFLD and even much better
when compared to other indices like TyG-BMI as a reflection of visceral fat accumulation.
This finding could help with clinical management, early diagnosis, and disease monitoring of
NAFLD patients.
However, I have the following comments to consider:
1- The "NAFLD" term has been updated since 2023 to overarching term "MASLD
(metabolic dysfunction-associated steatotic liver disease). I think that the NAFLD term was
applicable during your study period (1991-2021), but clear notification to terms updates /
replacement with MASLD term must be implemented over the manuscript's title, introduction,
methodology, results and discussion sections. Please refer to: [https://www.aasld.org/new-
masld-nomenclature]
2- Introduction:
# This part of the manuscript provides a comprehensive overview of NAFLD and the potential
role of the TyG-WC index. While the paper has mentioned the current and projected prevalence
of NAFLD, it doesn't provide specific data on its prevalence across different regions or
populations. Even the use of ultrasound and liver biopsy as diagnostic tools is briefly mentioned,
other non-invasive methods currently in use or under investigation (like LiverMultiScan,
Magnetic resonance elastography (MRE), radiomics, …etc.) should be also elaborated. Please
refer to: [Li G, Zhang X, Lin H, Liang LY, Wong GL, Wong VW. Non-invasive tests of non-
alcoholic fatty liver disease. Chin Med J (Engl). 2022 Jan 27;135(5):532-546. doi: 10.1097/
CM9.0000000000002027. PMID: 35089884; PMCID: PMC8920457].
#  Despite the absence of FDA-approved treatments and that weight loss as a primary treatment
of NAFLD, additional discussion of other management strategies or emerging therapies is highly
recommended to mention (such as Mediterranean diet, physical activity and exercise, bariatric
surgery). Please refer to: [Sun J, Jin X, Li Y. Current strategies for nonalcoholic fatty liver
disease treatment (Review). Int J Mol Med. 2024 Oct;54(4):88. doi: 10.3892/ijmm.2024.5412.
Epub 2024 Aug 12. PMID: 39129305; PMCID: PMC11335354.]
# The introduction could provide more context by discussing other predictive indices for
NAFLD that have been studied, beyond just mentioning HOMA-IR and TyG. In addition, further
explanation of the mechanisms underlying NAFLD development in general, and the role genetic
predisposition in NAFLD development in specific could be beneficial to address.
3- Results
4- Discussion
# The publication does not include a more thorough comparison to other recognized prognostic
indices, such as the TyG index or HOMA-IR, despite mentioning that TyG-WC may be more
useful than TyG-BMI in predicting NAFLD. A more thorough examination of the relative
advantages and disadvantages of these various indexes would be beneficial.
# The article also focuses of how insulin resistance contributes to the development of non-
alcoholic fatty liver disease (NAFLD) and how the elements of TyG-WC—waist circumference,
fasting plasma glucose, and triglycerides—are related to this process. But it could go into more
detail about the precise ways in which these elements influence the onset and course of NAFLD.
# According to the study, TyG-WC may be clinically useful for NAFLD management, disease
monitoring, and early diagnosis. It might, however, offer more precise information about how
this index might be applied to standard clinical procedures, including suggested cut-off values,
screening algorithms, or possible effects on patient outcomes.
# Whilst the study admits several shortcomings, such as the use of ultrasonography and the
preponderance of participants from a small number of nations, it might go into further detail
on the ramifications of these shortcomings and offer more targeted topics for future research
to fill in the gaps.
# In addition, potential confounding variables, such as dietary practices, physical activity, or
other comorbidities, that might affect the association between TyG-WC and NAFLD could be
covered in the study, along with how these variables were or could be taken into consideration
in subsequent research.
5- Conclusion
Conclusions should outline specific recommendations or guidance on how TyG-WC index can
be implemented in practice, and focus on placing the findings in a broader context, such as the
overall importance of early NAFLD detection and the potential impact of using TyG-WC as a
screening tool.