Review for 10.1186/s12876-024-03565-5 (2024)

Title: Association between the lymphocyte-to-high-density lipoprotein ratio and Metabolic
dysfunction-associated steatotic liver disease among US adults: a cross-sectional study from
NHANES 2017 to 2020
Version: 1 Date: 03 Oct 2024
Reviewer:  Amira A A Othman
Reviewer's report:
First of all
I want to congratulate the authors on their work. In this study, Tang et al used data from the 2017–
2020 National Health and Nutrition Examination Survey (NHANES) for adult Americans, this
research aims to explore the association between the lymphocyte-to-high-density lipoprotein
ratio and non-alcoholic fatty liver disease patients in adult US citizens.
NAFLD is characterized by subclinical inflammation8,9,10, and routine blood cells such as
platelets and white blood cells (WBCs) have been used as good biomarkers of systemic
inflammation. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte count ratio
(PLR), lymphocyte-monocyte ratio (LMR) and mean platelet volume (MPV) have recently been
considered as potential novel biomarkers of the inflammatory process. However, the association
between inflammatory markers and NAFLD remains uncertain*, **.
(*: doi.org/10.1186/s12974-021-02090-6, **: doi.org/10.1111/j.1478-3231.2011.02639.x).
The authors tried to contribute to this field of research with new findings, nevertheless, there is
an observation for which sufficient justification must be obtained.
In general:
1. The English writing level is shallow, and it is necessary to seek help from an English language
specialist to correct spelling and grammatical errors in the entire text.
In Title:
2. The authors may consider indicating that the study is an insight from NHANES with data
collected between March 2017 and 2020
3. “Non-alcoholic fatty liver disease (NAFLD)” is a broad expression that encompasses a
variety of conditions, including “non-alcoholic fatty liver (NAFLD, steatosis)”, intrahepatic
lipid accumulation without any secondary cause of liver fat accumulation such as heavy alcohol
consumption, of at least 5% of the liver weight that causes liver dysfunction and inflammation,
and advance to “non-alcoholic steatohepatitis (NASH)”, which is distinguished by liver fibrosis,
which advances to cirrhosis, and hepatocellular carcinoma in about 30–40% of cases. Thus, the
disease spectrum of NAFLD includes simple steatosis, steatohepatitis, fibrosis, and cirrhosis.
Which of them is the scope of your study to be identified in the title?
In Abstract section.
4. The background subsection:
-  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.
5.  The type of study: a population-based study.
6. In method subsection:
- please use “Using data from the National Health and Nutrition Examination Survey (NHANES)
database spanning from 2017 to 2020, a cross-sectional study included ***** participants was
performed to assess the relationship …….”.
- It would help if you described the aim of your statistical analysis. For example, Multivariate
linear regression models were used to examine the linear connection between the lymphocyte-
to-high-density lipoprotein ratio and non-alcoholic fatty liver disease. Fitted smoothing curves
and threshold effect analysis were used to describe the nonlinear relationship, etc.
- A two-part linear regression model was also used to estimate threshold effects.
- Nothing was mentioned about the participant’s age, sex, etc. in the abstract.
In the Introduction section:
7. Try to provide a summarized description of The National Health and Nutrition Examination
Survey (NHANES) in the background section rather than in the methodology 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.”.
8. Non-alcoholic fatty liver disease (NAFLD) nomenclature had several limitations, the name
chosen to replace NAFLD is metabolic dysfunction-associated steatotic liver disease (MASLD)
(Ref: doi.org/10.1186/s12876-024-03310-y).
9. Please focus on the relationship between the association between the LHR and MASLD
patients more than its relationship with cardiovascular disorders.
In the Methods section:
10. Please move the sentences defining the NHANES to the introduction section rather than the
methodology section.
11. Diagnosis of NAFLD
• Imaging, including “ultrasonography (US)”, “computed tomography (CT)”, and “magnetic
resonance imaging (MRI)”, are often used to diagnose MAFLD incidentally when routine liver
function lab shows abnormal biochemical test results. A liver biopsy is required to detect NASH
to determine the fibrosis advancement. Because a biopsy is intrusive and expensive, extensive
research has been undertaken to identify relevant blood biomarkers for the early prediction of
MAFLD.
(Ref.: doi.org/10.1186/s12876-024-03310-y).  Was the diagnosis made by questionnaire only?
• Why did not you utilize relevant biomarkers for MAFLD diagnosis?
12. Inclusion and exclusion criteria are Incomplete.
13. What was the source of the covariate data?
14. Statistical analysis:
- What is the test of significance used in the 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. What test of
significance is to be used?
- LHR and MASLD patients: Please discuss the following: “Three logistic regression models
were employed, with varying levels of adjustment for potential confounders. Model 1 was
unadjusted for covariates, while Model 2 included adjustments for age, sex, and race. Model
3 was further adjusted for education, marital status, PIR, BMI, alcohol intake, smoking status,
physical activity, hypertension, diabetes, high cholesterol levels, coronary heart disease, stroke,
and cancer.” Could you please explain how covariates were categorized? Why such diseases
were excluded (hypertension, diabetes, high cholesterol levels, coronary heart disease, stroke,
and cancer)?
- The generalized additive model and smoothed curve testing should be used to assess the
nonlinear relationship between sleep patterns, and dietary fiber intake, with liver fibrosis in
MAFLD patients.
In the Results section:
15. In all tables, please explain the abbreviations under tables.
16. 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 results with expected results, nothing was mentioned about
in the statistical analysis section.
17. Subgroup analyses must be performed to evaluate the effect of circadian syndrome on
gallstones and their stability in different populations. Subgroup analyses based on differences
in diagnostic components were performed to elaborate correlations. The results were presented
in forest plots using odds ratios (ORs) and 95% confidence intervals (CIs).
18. What about Quartile cut-off values?
19. Log2 logarithmic transformation shall be analyzed.
20. Future article readers may not know whether the above-mentioned variables were originally
collected as continuous data during data collection by NHANES, or whether the data were
originally categorized in the current study. In addition, in case there is a methodology article
published by NHANES or by other authors that specifically describes the variables, the authors
of the current study may consider citing that paper in the methodology section where the authors
of the current study mentioned the NHANES website.
In the Discussion section:
21. 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.
22. The discussion should explain how this ratio can help in the management of MAFLD.
23. Discuss the novelty of your study and how it differs from other scores and ratios:
• Association Between Monocyte to High-Density Lipoprotein Cholesterol Ratio and Risk of
MAFLD (doi: 10.3389/fmed.2022.898931, doi.org/10.1007/s11596-024-2919-6)
•  Association between platelet and Risk of MAFLD
(doi.org/10.1038/s41598-024-56796-7, doi: 10.1097/MEG.0000000000002439)
• Association between neutrophil-to-high-density lipoprotein cholesterol ratio and Risk of
MAFLD (doi.org/10.1186/s12876-024-03394-6).
24. Diseases diagnosis depending only on a questionnaire is to be considered one of the main
weaknesses.
In the conclusion section:
25. The conclusion should restate your main points and provide closure.