Review for 10.1186/s12876-025-03666-9 (2025)

Title: Serum Uric Acid as a Biomarker for Metabolic Dysfunction-Associated Steatotic Liver
Disease: Insights from Ultrasound Elastography in a Chinese Cohort
Version: 1 Date: 22 Dec 2024
Reviewer:  Amira A A Othman
Reviewer's report:
First of all,
Let me congratulate the authors for the enormous contribution they have made to this field. Here,
Chang and Liu use the data from 2018 to 2023 and the cohort of Chinese adults who participated
in the analysis to show the relationship of SUA levels with metabolic dysfunction-associated
Steatotic liver disease. This study uses advanced diagnostic techniques, such as ultrasound
elastography, and performs extensive statistical analyses, including logistic regression, restricted
cubic splines, and subgroup analyses. The authors seek to position SUA as a potential biomarker
of MASLD risk stratification and add important value to the evolving understanding of the
pathogenesis of MASLD.
MASLD, previously known as NAFLD, is a leading cause of chronic liver disease worldwide,
with prevalence rates ranging from 25% to 30% globally. The condition is closely linked
to obesity, type 2 diabetes, and metabolic syndrome, which are rising in prevalence across
many regions, including China*. Diagnostic tools like ultrasound elastography, which can
non-invasively assess hepatic steatosis and fibrosis, are revolutionizing the management of
MASLD**.  Previous studies have linked SUA to metabolic syndrome and NAFLD, but this
study uniquely examines its relationship with MASLD under the updated nomenclature and
criteria.
(*: DOI: 10.1016/j.jhep.2021.10.023,DOI: 10.1053/j.gastro.2020.11.051.  )
The authors handled the reviewer comments satisfactorily, nevertheless, there is an observation
for which sufficient justification must be obtained.
In general:
1. The manuscript used technical terms without definitions, which may hinder understanding
for broader readers. Please provide brief explanations.
2. Abbreviations must be fully written at their first use.
3. You have used the recently adopted name and abbreviation for the disease, MASLD, which
is Metabolic Dysfunction-Associated Steatotic Liver Disease, reflecting the update in the
understanding and putting into light the role of metabolic dysfunction. Why do you continue to
use the old term NAFLD, or Non-Alcoholic Fatty Liver Disease? The new term MASLD gets
rid of the out-of-date emphasis on ruling out alcohol as a cause, and it points toward metabolic
components, making the terminology more accurate and encompassing. The use of NAFLD
may be mislabeled and take away from consistency with contemporary standards of research
and clinical practices.
In the Title:
4. Revise your title to emphasize the significance of SUA as a biomarker and the role
of ultrasound elastography in metabolic dysfunction-associated Steatotic liver disease. For
example: "Serum Uric Acid as a Biomarker for Metabolic Dysfunction-Associated Steatotic
Liver Disease: Insights from Ultrasound Elastography in a Chinese Cohort."
In the Abstract section:
5. Include a sentence on the potential impact of Serum uric acid monitoring for metabolic
dysfunction-associated Steatotic liver disease management, such as informing preventive
strategies or early intervention.
In the Introduction section:
6. Discuss regional factors, such as dietary patterns, genetic predispositions, or rising metabolic
syndrome prevalence, that may make SUA an important marker for MASLD in the Chinese
population.
In the Methods section:
7. Please provide the participants' sociodemographic data.
8. How the sample size was calculated.
9. Inclusion and exclusion criteria must be provided.
10. How were patients with MAFLD diagnosed? What is the golden standard for diagnosis?
11. Are data collections retrospectively on a survey form? Nothing mentioned.
12. Include a justification for SUA tertile thresholds, referencing prior studies if applicable.
13. Discuss how the exclusion of participants with poor ultrasound imaging or other liver
diseases might bias the findings toward healthier individuals.
In the Results section:
14. In all tables, please explain the abbreviations under tables. Add key takeaways to each figure
or table caption to make the results more accessible. Simplify tables by focusing on the most
clinically relevant comparisons.
15. You can title the statistical test column as “Test of significance” and use U= for the Mann–
Whitney U test, T= for the T-test, and #2 = for the Chi-square test, etc., Although the Chi-square
test was used to compare observed and expected results, nothing was mentioned in the statistical
analysis section.
16. What were the patients' complaints?
17. Provide a brief interpretation of why these demographic differences may occur, linking to
biological mechanisms.
In the Discussion section:
18. The discussion section is one of the final parts of a research paper, in which an author
describes, analyzes, and interprets their findings. They explain the significance of those results
and tie everything back to the research question(s). In this manuscript, there is confusion
between what should be written in the introduction and discussion sections. Please reconstruct
the discussion section.
19. Expand on the biological mechanisms linking SUA and MASLD, such as its role in oxidative
stress, inflammation, or insulin resistance.
20. Compare SUA to other non-invasive biomarkers or indices for MASLD (e.g., Fibrosis-4
Index, NLR) to contextualize its relevance.
21. Discuss how SUA monitoring could complement ultrasound elastography in resource-
limited settings or routine screenings.
22. Discuss the novelty of your study.
23. Limitations should be in a dedicated subsection and discuss additional factors like: the cross-
sectional design precludes causal inference,  dietary factors, or unmeasured comorbidities, that
could influence SUA levels or MASLD risk, etc.
24. Discuss the future implications of your study. Discuss how SUA monitoring could align
with public health efforts to combat MASLD in populations with rising obesity and metabolic
syndrome prevalence.