Title: Estimated sdLDL-C as a biomarker of hepatic steatosis severity in MASLD: a
retrospective study
Version: 0 Date: 11 Feb 2025
Reviewer:  Amira A A Othman
Reviewer's report:
First of all
I want to congratulate the authors on their work. In this study, Jiang et al. aimed to investigates
the relationship between estimated small dense low-density lipoprotein cholesterol (EsdLDL-C)
and the severity of hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD).
It also assesses the correlation between EsdLDL-C and directly measured sdLDL-C (DsdLDL-
C), aiming to determine whether EsdLDL-C can serve as a cost-effective marker for identifying
patients with more severe forms of NAFLD.
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 be more informative and concise. , I suggest “ Estimated sdLDL-C as a Marker
of Hepatic Steatosis Severity in MAFLD: A Retrospective Study”.
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 subsection of the method in the abstract: Instead of "categorized into a mild (Mil)
group and a moderate and severe (Mod-Sev) group based on controlled attenuation parameter
(CAP) values," consider "Patients were classified by CAP values into mild and moderate-to-
severe groups."
5. In the results subsection in the abstract:   Improve numerical clarity and conciseness.
6. In the conclusion subsection in the abstract: should emphasize clinical implications rather
than just restating findings. Instead of "EsdLDL-C helping individuals with Mod-Sev steatosis
in NAFLD," consider "EsdLDL-C may serve as a practical, cost-effective biomarker for
identifying high-risk NAFLD patients."
In the Introduction section:
7. 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.
(*: https://doi.org/10.1186/s12876-024-03310-y).
8. Some sentences are overly complex. For example: "Early presentation of simple hepatic
steatosis and named non-alcoholic fatty liver (NAFL). However, if left untreated, some patients
of NAFL may progress to non-alcoholic steatohepatitis (NASH), liver cirrhosis (LC), and
ultimately hepatocellular carcinoma (HCC)." Suggested rewrite: "MAFLD initially manifests as
simple hepatic steatosis. If untreated, it can progress to non-alcoholic steatohepatitis, cirrhosis,
and even hepatocellular carcinoma (HCC)."
9. The aim of your study should be in the final paragraph. I suggest "Given the high prevalence
of NAFLD and the need for non-invasive, cost-effective biomarkers, this study explores whether
EsdLDL-C can serve as a reliable predictor of disease severity."
In the Methods section:
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. Grouping of patients: The Mild, Moderate, and Severe categories should be briefly justified
with clinical relevance (e.g., why CAP values of 259 and 292 were chosen as cutoffs).
15. The formula for EsdLDL-C calculation should be explained in simpler terms for broader
readership.
16. 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 the Results section:
17. In all tables, please explain the abbreviations under tables.
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., Although the Chi-square
test was used to compare observed and expected results, nothing was mentioned in the statistical
analysis section.
19. Ensure that table captions succinctly describe the content for standalone clarity.
20.  The comparison between groups (Mild vs. Mod-Sev) is well-presented but could benefit
from a summary statement before diving into details. Example: "Compared to the mild group, the
moderate-to-severe group had significantly higher EsdLDL-C, BMI, and CAP values, indicating
a strong association between lipid metabolism and hepatic steatosis."
21. Tables and figures should be referenced more explicitly. Instead of "Figure 2 presents the
ROC curve," consider "As shown in Figure 2, an EsdLDL-C cutoff of 28.5 mg/dL effectively
predicts Mod-Sev steatosis (AUC = 0.825, 95% CI: 0.784-0.867, P < 0.001)."
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 and discussion sections. Please reconstruct
the discussion section.
23. Discuss the novelty of your study regarding previously published papers.
24. The clinical significance of findings should be more prominent. Example: Instead of
"EsdLDL-C was significantly correlated with hepatic steatosis severity," try "These findings
suggest EsdLDL-C could be a useful, non-invasive marker for identifying NAFLD patients at
risk for disease progression."
25. The discussion briefly mentions regional bias, but it would be stronger if it suggested how
future studies could address these limitations (e.g., larger sample size, multi-center study).
Title: Estimated sdLDL-C as a biomarker of hepatic steatosis severity in MASLD: a
retrospective study
Version: 0 Date: 11 Feb 2025
Reviewer:  Amira A A Othman
Reviewer's report:
First of all
I want to congratulate the authors on their work. In this study, Jiang et al. aimed to investigates
the relationship between estimated small dense low-density lipoprotein cholesterol (EsdLDL-C)
and the severity of hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD).
It also assesses the correlation between EsdLDL-C and directly measured sdLDL-C (DsdLDL-
C), aiming to determine whether EsdLDL-C can serve as a cost-effective marker for identifying
patients with more severe forms of NAFLD.
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 be more informative and concise. , I suggest “ Estimated sdLDL-C as a Marker
of Hepatic Steatosis Severity in MAFLD: A Retrospective Study”.
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 subsection of the method in the abstract: Instead of "categorized into a mild (Mil)
group and a moderate and severe (Mod-Sev) group based on controlled attenuation parameter
(CAP) values," consider "Patients were classified by CAP values into mild and moderate-to-
severe groups."
5. In the results subsection in the abstract:   Improve numerical clarity and conciseness.
6. In the conclusion subsection in the abstract: should emphasize clinical implications rather
than just restating findings. Instead of "EsdLDL-C helping individuals with Mod-Sev steatosis
in NAFLD," consider "EsdLDL-C may serve as a practical, cost-effective biomarker for
identifying high-risk NAFLD patients."
In the Introduction section:
7. 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.
(*: https://doi.org/10.1186/s12876-024-03310-y).
8. Some sentences are overly complex. For example: "Early presentation of simple hepatic
steatosis and named non-alcoholic fatty liver (NAFL). However, if left untreated, some patients
of NAFL may progress to non-alcoholic steatohepatitis (NASH), liver cirrhosis (LC), and
ultimately hepatocellular carcinoma (HCC)." Suggested rewrite: "MAFLD initially manifests as
simple hepatic steatosis. If untreated, it can progress to non-alcoholic steatohepatitis, cirrhosis,
and even hepatocellular carcinoma (HCC)."
9. The aim of your study should be in the final paragraph. I suggest "Given the high prevalence
of NAFLD and the need for non-invasive, cost-effective biomarkers, this study explores whether
EsdLDL-C can serve as a reliable predictor of disease severity."
In the Methods section:
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. Grouping of patients: The Mild, Moderate, and Severe categories should be briefly justified
with clinical relevance (e.g., why CAP values of 259 and 292 were chosen as cutoffs).
15. The formula for EsdLDL-C calculation should be explained in simpler terms for broader
readership.
16. 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 the Results section:
17. In all tables, please explain the abbreviations under tables.
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., Although the Chi-square
test was used to compare observed and expected results, nothing was mentioned in the statistical
analysis section.
19. Ensure that table captions succinctly describe the content for standalone clarity.
20.  The comparison between groups (Mild vs. Mod-Sev) is well-presented but could benefit
from a summary statement before diving into details. Example: "Compared to the mild group, the
moderate-to-severe group had significantly higher EsdLDL-C, BMI, and CAP values, indicating
a strong association between lipid metabolism and hepatic steatosis."
21. Tables and figures should be referenced more explicitly. Instead of "Figure 2 presents the
ROC curve," consider "As shown in Figure 2, an EsdLDL-C cutoff of 28.5 mg/dL effectively
predicts Mod-Sev steatosis (AUC = 0.825, 95% CI: 0.784-0.867, P < 0.001)."
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 and discussion sections. Please reconstruct
the discussion section.
23. Discuss the novelty of your study regarding previously published papers.
24. The clinical significance of findings should be more prominent. Example: Instead of
"EsdLDL-C was significantly correlated with hepatic steatosis severity," try "These findings
suggest EsdLDL-C could be a useful, non-invasive marker for identifying NAFLD patients at
risk for disease progression."
25. The discussion briefly mentions regional bias, but it would be stronger if it suggested how
future studies could address these limitations (e.g., larger sample size, multi-center study).
Please review this paper.
user
Title: Estimated sdLDL-C as a biomarker of hepatic steatosis severity in MASLD: a
retrospective study
Version: 0 Date: 11 Feb 2025
Reviewer:  Amira A A Othman
Reviewer's report:
First of all
I want to congratulate the authors on their work. In this study, Jiang et al. aimed to investigates
the relationship between estimated small dense low-density lipoprotein cholesterol (EsdLDL-C)
and the severity of hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD).
It also assesses the correlation between EsdLDL-C and directly measured sdLDL-C (DsdLDL-
C), aiming to determine whether EsdLDL-C can serve as a cost-effective marker for identifying
patients with more severe forms of NAFLD.
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 be more informative and concise. , I suggest “ Estimated sdLDL-C as a Marker
of Hepatic Steatosis Severity in MAFLD: A Retrospective Study”.
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 subsection of the method in the abstract: Instead of "categorized into a mild (Mil)
group and a moderate and severe (Mod-Sev) group based on controlled attenuation parameter
(CAP) values," consider "Patients were classified by CAP values into mild and moderate-to-
severe groups."
5. In the results subsection in the abstract:   Improve numerical clarity and conciseness.
6. In the conclusion subsection in the abstract: should emphasize clinical implications rather
than just restating findings. Instead of "EsdLDL-C helping individuals with Mod-Sev steatosis
in NAFLD," consider "EsdLDL-C may serve as a practical, cost-effective biomarker for
identifying high-risk NAFLD patients."
In the Introduction section:
7. 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.
(*: https://doi.org/10.1186/s12876-024-03310-y).
8. Some sentences are overly complex. For example: "Early presentation of simple hepatic
steatosis and named non-alcoholic fatty liver (NAFL). However, if left untreated, some patients
of NAFL may progress to non-alcoholic steatohepatitis (NASH), liver cirrhosis (LC), and
ultimately hepatocellular carcinoma (HCC)." Suggested rewrite: "MAFLD initially manifests as
simple hepatic steatosis. If untreated, it can progress to non-alcoholic steatohepatitis, cirrhosis,
and even hepatocellular carcinoma (HCC)."
9. The aim of your study should be in the final paragraph. I suggest "Given the high prevalence
of NAFLD and the need for non-invasive, cost-effective biomarkers, this study explores whether
EsdLDL-C can serve as a reliable predictor of disease severity."
In the Methods section:
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. Grouping of patients: The Mild, Moderate, and Severe categories should be briefly justified
with clinical relevance (e.g., why CAP values of 259 and 292 were chosen as cutoffs).
15. The formula for EsdLDL-C calculation should be explained in simpler terms for broader
readership.
16. 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 the Results section:
17. In all tables, please explain the abbreviations under tables.
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., Although the Chi-square
test was used to compare observed and expected results, nothing was mentioned in the statistical
analysis section.
19. Ensure that table captions succinctly describe the content for standalone clarity.
20.  The comparison between groups (Mild vs. Mod-Sev) is well-presented but could benefit
from a summary statement before diving into details. Example: "Compared to the mild group, the
moderate-to-severe group had significantly higher EsdLDL-C, BMI, and CAP values, indicating
a strong association between lipid metabolism and hepatic steatosis."
21. Tables and figures should be referenced more explicitly. Instead of "Figure 2 presents the
ROC curve," consider "As shown in Figure 2, an EsdLDL-C cutoff of 28.5 mg/dL effectively
predicts Mod-Sev steatosis (AUC = 0.825, 95% CI: 0.784-0.867, P < 0.001)."
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 and discussion sections. Please reconstruct
the discussion section.
23. Discuss the novelty of your study regarding previously published papers.
24. The clinical significance of findings should be more prominent. Example: Instead of
"EsdLDL-C was significantly correlated with hepatic steatosis severity," try "These findings
suggest EsdLDL-C could be a useful, non-invasive marker for identifying NAFLD patients at
risk for disease progression."
25. The discussion briefly mentions regional bias, but it would be stronger if it suggested how
future studies could address these limitations (e.g., larger sample size, multi-center study).
assistant