Review for 10.1186/s12876-025-03612-9 (2025)

Title: Association Between Neutrophil-Albumin Ratio and Ultrasound-Defined Metabolic
Dysfunction-Associated Fatty Liver Disease in U.S. Adults: Evidence from NHANES
2017-2018
Version: 0 Date: 29 Dec 2024
Reviewer:  Amira A A Othman
Reviewer's report:
First of all
I want to congratulate the authors on their work. In this study, Wu et al. aimed to evaluate the
association between the neutrophil-albumin ratio (NAR) and non-alcoholic fatty liver disease
(NAFLD) defined by ultrasound and to construct predictive models in the 2017-2018 NHANES
for adult Americans.
Non-alcoholic fatty liver disease (NAFLD) is recognized as the most prevalent chronic liver
disease, impacting about 30% of global individuals, with the potential to progress to advanced
hepatic fibrosis and end-stage liver diseases eventually [*]. In June 2023, a multi-society
committee of international experts was gathered, and new terminology was adopted to reduce
stigma and increase disease awareness [**]. A new terminology, Steatotic liver disease (SLD),
replaces “fatty liver disease” as the umbrella term. Under subgroups of SLD, NAFLD has been
renamed as metabolic dysfunction-associated Steatotic liver disease (MASLD) [**]. NAFLD/
MASLD is closely related to metabolic syndrome (MetS) and its associated components of
hypertension, type 2 diabetes mellitus, dyslipidemia, and obesity[***].
(*:doi: 10.1097/HEP.0000000000000004, **: doi: 10.1016/j.jhep.2023.06.003, ***  doi:
10.1111/apt.17308).
The authors handled the reviewer comments satisfactorily, nevertheless, there is an observation
for which sufficient justification must be obtained.
In general:
1. The writing quality needs improvement, and it would be beneficial to consult an English
language expert to address spelling and grammatical issues throughout the text.
2. Abbreviations must be fully written at their first appearance.
In Title:
1. The title should indicate the age and locality of the study population at which the National
Health and Nutrition Examination Survey (NHANES) was performed. , I suggest “Association
Between Neutrophil-Albumin Ratio and Ultrasound-Defined Metabolic Associated Fatty Liver
Disease in U.S. Adults: Evidence from NHANES 2017-2018”.
In Abstract section
2. The background subsection in the abstract :
-  Should be the shortest part of the abstract. It should briefly outline the following information:
What is already known about the subject, related to the paper in question. What is not known
about the subject and hence what the study intended to examine (or what the paper seeks to
present)? Please reconstruct it properly.
3.  The type of study: a population-based study.
4. In the method subsection in the abstract :
- Nothing was mentioned about the participant's age, sex, ethnicity, etc.
- It would help if you described the aim of your statistical analysis.
In the Introduction section:
5. Try to provide a summarized description of The National Health and Nutrition Examination
Survey (NHANES) in the background section. You may use the following:
“NHANES (www.cdc.gov/nchs/nhanes) is designed to assess the health and nutritional status
of adults and children in the United States. The survey is distinctive in that it incorporates
both physical examinations and interviews. Several cross-sectional, nationally representative
health examination surveys are part of the NHANES program. Questions about demographics,
health insurance status, dietary habits, acute and chronic medical issues, mental health, and
prescription drug use are all included in the health interview. Exam components can change
between survey cycles but typically include blood pressure, dental exams, vision, hearing,
dermatology, fitness, balance and strength testing, respiratory testing, taste and smell, and
body measurements (weight, height, skin folds, body composition scans). Hematology, organ
and endocrine function (e.g., thyroid, kidney), environmental exposure, dietary biomarkers,
metabolic and cardiovascular health, and infectious disease are a few examples of laboratory
components.”.
6. MAFLD must replace NAFLD:
“In contrast to NAFLD, MAFLD does not necessitate ruling out other liver disease causes, such
as viral hepatitis or heavy alcohol use*. The new name chosen to replace NAFLD reflected the
disease etiology better and conveyed a more practical approach in daily clinical practice than
NAFLD, considering its close association with metabolic syndrome**. Please discuss the new
nomenclature in more detail.
(*: Doi: 10.1016/j.jhep.2020.03.039, **: doi: 10.1097/HEP.0000000000000520)
7. Highlight the unique contribution of this study, particularly the novel use of NAR for NAFLD
diagnosis compared to existing biomarkers.
In the Methods section:
8. Please move the sentences defining the NHANES to the introduction section rather than the
methodology section.
9. The study utilized the 2017-2018 NHANES survey cycle, why did you choose the study
survey cycle? The survey includes study cycles from 2001 to 2020.
10. Please provide the participants' sociodemographic data.
11. How the sample size was calculated.
12. Mention ethical approval earlier in the methodology to emphasize compliance.
13. Provide more details on the exclusion criteria to ensure reproducibility (e.g., specific
thresholds for "missing data").
14. Clarify the rationale for choosing CAP # 285 dB/m as the NAFLD threshold and address
potential limitations of using this criterion.
15. Statistical analysis:
-   The Mann–Whitney U test is a nonparametric test and involves the summation of ranks. The
Mann–Whitney U test is applied to independent samples. T-test is used to compare the mean of a
continuous variable between a maximum of 2 groups. The Kruskal–Wallis test is a statistical test
used to compare two or more groups for a continuous or discrete variable. The Wilcoxon rank-
sum test is used to compare two independent samples, while the Wilcoxon signed-rank test is
used to compare two related samples, matched samples, or to conduct a paired difference test of
repeated measurements on a single sample to assess whether their population mean ranks differ.
Analysis of variance (ANOVA) is a statistical test used to assess the difference between the
means of more than two groups. How did you choose the proper test during your result analysis?
- In logistic regression analyses, is it multivariate or univariate? Please identify.
In the Results section:
16. In all tables, please explain the abbreviations under tables.
17. 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.
18. Ensure that table captions succinctly describe the content for standalone clarity.
19. Elaborate on the implications of the threshold effect at NAR = 1.436, linking it to potential
clinical thresholds for intervention.
In the Discussion section:
20. 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.
21. Compare the predictive power of NAR to other biomarkers studied in MAFLD (e.g., NLR,
PLR), emphasizing its advantages and limitations.
22. Address potential confounders that could influence the observed association between NAR
and CAP.
23. Discuss how the random forest model's predictive performance translates into clinical
practice.
24. Discuss the novelty of your study regarding previously published papers with the same aim
and title
( doi: 10.3390/nu15081892. , doi: 10.3389/fnut.2024.1368459), via for example:
• Investigate and report how NAR performs in subpopulations (e.g., by age, gender,
comorbidities) to show its adaptability.
• Compare the performance of NAR directly with indices previously used.
• Highlight the combination of NAR with key demographic, clinical, and biochemical variables
(e.g., age, BMI, ALT) for enhanced predictive models.
• perform subgroup analyses or sensitivity tests to identify the most critical variables contributing
to MAFLD risk. Etc.