Title: Novel non-HDLc/HDLc Ratio for Predicting MASLD: A Cross-Sectional Study in a
Chinese Health Screening Population
Version: 2 Date: 02 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, Hong et al research aims
to establish and validate a prediction model that combines the non-HDL cholesterol-to-HDL
cholesterol ratio (non-HDL: HDL) with other lipid markers to predict MAFLD.
Recently, growing evidence suggests that non-HDL cholesterol and the non-HDL cholesterol-
to-HDL cholesterol ratio (non-HDLc: HDLc) are stronger metabolic syndrome and insulin
resistance predictors than LDL in the general population, although epidemiological data among
diabetic patients are more limited*. The non-HDL cholesterol-to-HDL cholesterol ratio (non-
HDL: HDL) could indicate combined lipid problems and was demonstrated as a better predictor
for multiple dyslipidemia-related disorders, such as coronary heart disease (CHD), insulin
resistance, metabolic syndrome, and chronic kidney disease than single lipoprotein or the apoB/
apoA1 ratio. A recent observational study of type 2 diabetes also found that the non-HDLc/HDLc
ratio had a stronger effect on CHD risk than non-HDLc. However, it is still unclear whether the
non-HDLc/HDLc ratio is an equal or a better predictor for the incidence of NAFLD**.
(*: doi.org/10.1016/j.ijcard.2013.03.027, ** doi.org/10.1186/s12944-018-0848-8).
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 poor, and it is necessary to seek help from an English language
specialist to correct spelling and grammatical errors in the entire text.
2. Abbreviations must be fully written before the first use, for example: NHHR, NAFLD, etc.
In Title:
3. Your title should give readers a clear idea of what your essay is about while also capturing
their interest. Use concise language and avoid overly long or complex titles. Avoid ambiguous
abbreviations.
4. Adding the locality of the study would improve the vision. Cholesterol levels vary by race
and ethnicity as well as gender, according to the CDC. The same for age (doi.org/10.1186/
s12944-020-01421-5).
5. “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 MASLD 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
6. The background subsection:
-  Should be the shortest part of the abstract. It should very 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 consider adding.
- Objective: to elucidate the aim of the study.
7.  Is this study a population-based study?
8. In method subsection:
- 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 lipids and
MAFLD . Fitted smoothing curves and threshold effect analysis were used to describe the
nonlinear relationship, etc.
- Nothing was mentioned about the participant’s age, sex, etc. in the abstract.
9. In conclusion subsection
- State the conclusion concisely and avoid overstatements.
In the Introduction section:
10. 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).
11. Please focus on the relationship between lipids and NAFLD patients more than its
relationship with cardiovascular disorders.
12. Dyslipidemia, needs better discussion (Classification, Etiology, Symptoms and Signs,
Diagnosis, Screening, and Treatment).
13. The abbreviation “NHHR” is not universal. It is commonly abbreviated to “non-HDL: HDL”
or “non-HDLc/HDLc” ratio.
In the Methods section:
14. 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. (doi.org/10.1186/s12876-024-03310-y)
- Why did not you utilize relevant biomarkers for MAFLD diagnosis?
15. Inclusion and exclusion criteria are missing
16. Statistical analysis:
- What is the source of covariates in the three models of logistic regression
- Why did you choose mean ± standard error rather than mean ± standard deviation?
-  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. Why did you
choose the Kruskal–Wallis test?
- 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:
17. Use Table 1 to compare the baseline demographic, clinical, and biochemical characteristics
of individuals by tertiles of the non-HDLc/HDLc ratio.
18. 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.
19. 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).
20. What about Quartile cut-off values?
21. Log2 logarithmic transformation shall be analyzed.
In the Discussion section:
22. 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 section and the discussion section. Please reconstruct
the discussion section.
23. Discuss the novelty of your study in the notion of others
(doi.org/10.1186/s12944-020-01421-5, doi.org/10.1186/s12944-018-0720-x, doi.org/10.1186/
s12944-018-0848-8, doi.org/10.1186/2193-1801-3-407)
In the conclusion section:
24. The conclusion should restate your main points and provide closure.
Title: Novel non-HDLc/HDLc Ratio for Predicting MASLD: A Cross-Sectional Study in a
Chinese Health Screening Population
Version: 2 Date: 02 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, Hong et al research aims
to establish and validate a prediction model that combines the non-HDL cholesterol-to-HDL
cholesterol ratio (non-HDL: HDL) with other lipid markers to predict MAFLD.
Recently, growing evidence suggests that non-HDL cholesterol and the non-HDL cholesterol-
to-HDL cholesterol ratio (non-HDLc: HDLc) are stronger metabolic syndrome and insulin
resistance predictors than LDL in the general population, although epidemiological data among
diabetic patients are more limited*. The non-HDL cholesterol-to-HDL cholesterol ratio (non-
HDL: HDL) could indicate combined lipid problems and was demonstrated as a better predictor
for multiple dyslipidemia-related disorders, such as coronary heart disease (CHD), insulin
resistance, metabolic syndrome, and chronic kidney disease than single lipoprotein or the apoB/
apoA1 ratio. A recent observational study of type 2 diabetes also found that the non-HDLc/HDLc
ratio had a stronger effect on CHD risk than non-HDLc. However, it is still unclear whether the
non-HDLc/HDLc ratio is an equal or a better predictor for the incidence of NAFLD**.
(*: doi.org/10.1016/j.ijcard.2013.03.027, ** doi.org/10.1186/s12944-018-0848-8).
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 poor, and it is necessary to seek help from an English language
specialist to correct spelling and grammatical errors in the entire text.
2. Abbreviations must be fully written before the first use, for example: NHHR, NAFLD, etc.
In Title:
3. Your title should give readers a clear idea of what your essay is about while also capturing
their interest. Use concise language and avoid overly long or complex titles. Avoid ambiguous
abbreviations.
4. Adding the locality of the study would improve the vision. Cholesterol levels vary by race
and ethnicity as well as gender, according to the CDC. The same for age (doi.org/10.1186/
s12944-020-01421-5).
5. “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 MASLD 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
6. The background subsection:
-  Should be the shortest part of the abstract. It should very 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 consider adding.
- Objective: to elucidate the aim of the study.
7.  Is this study a population-based study?
8. In method subsection:
- 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 lipids and
MAFLD . Fitted smoothing curves and threshold effect analysis were used to describe the
nonlinear relationship, etc.
- Nothing was mentioned about the participant’s age, sex, etc. in the abstract.
9. In conclusion subsection
- State the conclusion concisely and avoid overstatements.
In the Introduction section:
10. 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).
11. Please focus on the relationship between lipids and NAFLD patients more than its
relationship with cardiovascular disorders.
12. Dyslipidemia, needs better discussion (Classification, Etiology, Symptoms and Signs,
Diagnosis, Screening, and Treatment).
13. The abbreviation “NHHR” is not universal. It is commonly abbreviated to “non-HDL: HDL”
or “non-HDLc/HDLc” ratio.
In the Methods section:
14. 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. (doi.org/10.1186/s12876-024-03310-y)
- Why did not you utilize relevant biomarkers for MAFLD diagnosis?
15. Inclusion and exclusion criteria are missing
16. Statistical analysis:
- What is the source of covariates in the three models of logistic regression
- Why did you choose mean ± standard error rather than mean ± standard deviation?
-  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. Why did you
choose the Kruskal–Wallis test?
- 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:
17. Use Table 1 to compare the baseline demographic, clinical, and biochemical characteristics
of individuals by tertiles of the non-HDLc/HDLc ratio.
18. 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.
19. 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).
20. What about Quartile cut-off values?
21. Log2 logarithmic transformation shall be analyzed.
In the Discussion section:
22. 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 section and the discussion section. Please reconstruct
the discussion section.
23. Discuss the novelty of your study in the notion of others
(doi.org/10.1186/s12944-020-01421-5, doi.org/10.1186/s12944-018-0720-x, doi.org/10.1186/
s12944-018-0848-8, doi.org/10.1186/2193-1801-3-407)
In the conclusion section:
24. The conclusion should restate your main points and provide closure.
Please review this paper.
user
Title: Novel non-HDLc/HDLc Ratio for Predicting MASLD: A Cross-Sectional Study in a
Chinese Health Screening Population
Version: 2 Date: 02 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, Hong et al research aims
to establish and validate a prediction model that combines the non-HDL cholesterol-to-HDL
cholesterol ratio (non-HDL: HDL) with other lipid markers to predict MAFLD.
Recently, growing evidence suggests that non-HDL cholesterol and the non-HDL cholesterol-
to-HDL cholesterol ratio (non-HDLc: HDLc) are stronger metabolic syndrome and insulin
resistance predictors than LDL in the general population, although epidemiological data among
diabetic patients are more limited*. The non-HDL cholesterol-to-HDL cholesterol ratio (non-
HDL: HDL) could indicate combined lipid problems and was demonstrated as a better predictor
for multiple dyslipidemia-related disorders, such as coronary heart disease (CHD), insulin
resistance, metabolic syndrome, and chronic kidney disease than single lipoprotein or the apoB/
apoA1 ratio. A recent observational study of type 2 diabetes also found that the non-HDLc/HDLc
ratio had a stronger effect on CHD risk than non-HDLc. However, it is still unclear whether the
non-HDLc/HDLc ratio is an equal or a better predictor for the incidence of NAFLD**.
(*: doi.org/10.1016/j.ijcard.2013.03.027, ** doi.org/10.1186/s12944-018-0848-8).
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 poor, and it is necessary to seek help from an English language
specialist to correct spelling and grammatical errors in the entire text.
2. Abbreviations must be fully written before the first use, for example: NHHR, NAFLD, etc.
In Title:
3. Your title should give readers a clear idea of what your essay is about while also capturing
their interest. Use concise language and avoid overly long or complex titles. Avoid ambiguous
abbreviations.
4. Adding the locality of the study would improve the vision. Cholesterol levels vary by race
and ethnicity as well as gender, according to the CDC. The same for age (doi.org/10.1186/
s12944-020-01421-5).
5. “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 MASLD 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
6. The background subsection:
-  Should be the shortest part of the abstract. It should very 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 consider adding.
- Objective: to elucidate the aim of the study.
7.  Is this study a population-based study?
8. In method subsection:
- 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 lipids and
MAFLD . Fitted smoothing curves and threshold effect analysis were used to describe the
nonlinear relationship, etc.
- Nothing was mentioned about the participant’s age, sex, etc. in the abstract.
9. In conclusion subsection
- State the conclusion concisely and avoid overstatements.
In the Introduction section:
10. 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).
11. Please focus on the relationship between lipids and NAFLD patients more than its
relationship with cardiovascular disorders.
12. Dyslipidemia, needs better discussion (Classification, Etiology, Symptoms and Signs,
Diagnosis, Screening, and Treatment).
13. The abbreviation “NHHR” is not universal. It is commonly abbreviated to “non-HDL: HDL”
or “non-HDLc/HDLc” ratio.
In the Methods section:
14. 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. (doi.org/10.1186/s12876-024-03310-y)
- Why did not you utilize relevant biomarkers for MAFLD diagnosis?
15. Inclusion and exclusion criteria are missing
16. Statistical analysis:
- What is the source of covariates in the three models of logistic regression
- Why did you choose mean ± standard error rather than mean ± standard deviation?
-  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. Why did you
choose the Kruskal–Wallis test?
- 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:
17. Use Table 1 to compare the baseline demographic, clinical, and biochemical characteristics
of individuals by tertiles of the non-HDLc/HDLc ratio.
18. 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.
19. 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).
20. What about Quartile cut-off values?
21. Log2 logarithmic transformation shall be analyzed.
In the Discussion section:
22. 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 section and the discussion section. Please reconstruct
the discussion section.
23. Discuss the novelty of your study in the notion of others
(doi.org/10.1186/s12944-020-01421-5, doi.org/10.1186/s12944-018-0720-x, doi.org/10.1186/
s12944-018-0848-8, doi.org/10.1186/2193-1801-3-407)
In the conclusion section:
24. The conclusion should restate your main points and provide closure.
assistant