Title: Evaluating the Efficacy of 8 Non-invasive Models in Predicting MASLD and Its
Progression: A Prospective Study
Version: 5 Date: 04 Sep 2024
Reviewer's report:
I read with great interest the revised manuscript by Yang et al who aimed to compare the accuracy
of 8 different non invasive models of steatosis in MASLD with MRI-PDFF as the reference
standard as well as the performance of these tests in the prediction of progression of steatosis in
one year time. I have a few comments regarding this paper.
1. The paper needs some English editing. For example:
2. Page 2, "What is already known on this topic", lines: 13, 14: "and early diagnosis and long-
term follow-up using noninvasive methods are needed" - Please rephrase
3. Page 2, :What this study adds", lines 18: Please expand LFC abbreviation
4. As it is written in the abstract (and in main text as well) it is not clear for the readers (especially
not hepatologists) that you are going to compare non-invasive tests of steatosis. Also when you
say progression, you need to clarify that you mean progression of steatosis. You have to indicate
that steatosis this is the main focus of the study.
5. Methods, page 4, line 9: :To investigate the natural course of metabolic associated steatosis
liver disease (MASLD) over a one-year interval, with lifestyle education at enrollment and each
follow-up visit but no pharmacological intervention, except for comorbid conditions requiring
medication (e.g., hypertension, diabetes, hyperlipidemia)" - You need to rephrase the sentence
6. Methods, page 4, line 9: You have already given the expansion of MASLD - please use only
the abbreviation
7. Study design: Please give more details for the design of the study. It is not very clear
how you enrolled patients. Was there a past record of patients with steatosis that you later
enrolled? Did you collect the data prospectively? Which was the time point that patients were
incuded in the study? Was it the day of MRI-PDFF performance? when was the MRI-PDFF
performed in relation to the date of enrollment or in relation to liver biopsy? Give also here the
definitions of degree of steatosis (no steatosis, mild, moderate, severe) according to the MRI-
PDFF measurements
8. Methods, page 6, line 24, "the nonalcoholic fatty liver disease activity score (NAS) were
evaluated": please rephrase
9. Methods, page 6, line 33: Please change MAFLD to MASLD
10. The paragraph of sensitivity analysis should be moved above statistical analysis
11. Tables in general: You have to provide a footnote with all abbreviations used in each table
expanded. Also you have a note that contains statistical analysis performed in the analysis. This
should be deleted and repsrted to the statistical analysis section. Moreover, in the parentheses
of quantitative data you do not explain that this number is the IQR. You have to explain it in the
variables column as you do for (%). For example: Age (years), median (IQR)
12. Results, Page 9, lines 12-17 and 21-25: Delete all data in parentheses as already presented
in Tables
13. Results, Page 9, lines 19-20: Please rephrase as "the equations of the models used in the
study are presented in Suppl Table 1"
14. Considering that 108 patients underwent liver biopsy, please report other information related
to histology apart from MASH presence e.g. fibrosis and METAVIR score, NAS score etc
15. Results, page 10, line 2: Please delete "KNAFLD performed better"
16. Results, page 11, line 14: Please change NAFLD to MASLD
17. I think that it is somewhat misleading to label patients with mild steatosis as mild MASLD,
those with moderate steatosis as moderate MASLD etc. Perhaps you should rename the
categories as: Mild steatosis-MASLD, moderate steatosis-MASLD etc
18. Also I suggest to change the Keep category to Stable.
19. Results, page 13, lines 13-17, "suggesting...group". Not fit in the Results section. You could
mention this comment in the Discussion
20. Results, page 13, line  21: Please delete "FAST performed best"
21. Results, Page 14, lines 4-6: "the AUCs of FAST and KNAFLD were the top 2 highest (AUC:
0.87 and 0.84, respectively), and FLI, Liver Fat Equation and Liver Fat Score also performed
well (AUC: 0.83, 0.80 and 0.78, respectively)" - I would suggest to present this results in a Table
that demonstrates the performance of this models to predict statosis progression
22.Results, Page 16, lines 1-4, "This study evaluated eight clinical prediction models for
MASLD using MRI-PDFF, validating them with LSM and histopathological results. KNAFLD
and FAST emerged as superior tools for assessing MASLD severity and progression, making
them valuable assets in managing MASLD patients": Delete or move to the Discussion section
23. Discussion, page 16, lines 6-19: I would suggest this information to be moved in the
Introduction section.
24. Another limitation of the study that needs to be addressed is the lack of an extrinsic validation
cohort to confrm the accuracy of the estimated cut-offs for each score
Title: Evaluating the Efficacy of 8 Non-invasive Models in Predicting MASLD and Its
Progression: A Prospective Study
Version: 5 Date: 04 Sep 2024
Reviewer's report:
I read with great interest the revised manuscript by Yang et al who aimed to compare the accuracy
of 8 different non invasive models of steatosis in MASLD with MRI-PDFF as the reference
standard as well as the performance of these tests in the prediction of progression of steatosis in
one year time. I have a few comments regarding this paper.
1. The paper needs some English editing. For example:
2. Page 2, "What is already known on this topic", lines: 13, 14: "and early diagnosis and long-
term follow-up using noninvasive methods are needed" - Please rephrase
3. Page 2, :What this study adds", lines 18: Please expand LFC abbreviation
4. As it is written in the abstract (and in main text as well) it is not clear for the readers (especially
not hepatologists) that you are going to compare non-invasive tests of steatosis. Also when you
say progression, you need to clarify that you mean progression of steatosis. You have to indicate
that steatosis this is the main focus of the study.
5. Methods, page 4, line 9: :To investigate the natural course of metabolic associated steatosis
liver disease (MASLD) over a one-year interval, with lifestyle education at enrollment and each
follow-up visit but no pharmacological intervention, except for comorbid conditions requiring
medication (e.g., hypertension, diabetes, hyperlipidemia)" - You need to rephrase the sentence
6. Methods, page 4, line 9: You have already given the expansion of MASLD - please use only
the abbreviation
7. Study design: Please give more details for the design of the study. It is not very clear
how you enrolled patients. Was there a past record of patients with steatosis that you later
enrolled? Did you collect the data prospectively? Which was the time point that patients were
incuded in the study? Was it the day of MRI-PDFF performance? when was the MRI-PDFF
performed in relation to the date of enrollment or in relation to liver biopsy? Give also here the
definitions of degree of steatosis (no steatosis, mild, moderate, severe) according to the MRI-
PDFF measurements
8. Methods, page 6, line 24, "the nonalcoholic fatty liver disease activity score (NAS) were
evaluated": please rephrase
9. Methods, page 6, line 33: Please change MAFLD to MASLD
10. The paragraph of sensitivity analysis should be moved above statistical analysis
11. Tables in general: You have to provide a footnote with all abbreviations used in each table
expanded. Also you have a note that contains statistical analysis performed in the analysis. This
should be deleted and repsrted to the statistical analysis section. Moreover, in the parentheses
of quantitative data you do not explain that this number is the IQR. You have to explain it in the
variables column as you do for (%). For example: Age (years), median (IQR)
12. Results, Page 9, lines 12-17 and 21-25: Delete all data in parentheses as already presented
in Tables
13. Results, Page 9, lines 19-20: Please rephrase as "the equations of the models used in the
study are presented in Suppl Table 1"
14. Considering that 108 patients underwent liver biopsy, please report other information related
to histology apart from MASH presence e.g. fibrosis and METAVIR score, NAS score etc
15. Results, page 10, line 2: Please delete "KNAFLD performed better"
16. Results, page 11, line 14: Please change NAFLD to MASLD
17. I think that it is somewhat misleading to label patients with mild steatosis as mild MASLD,
those with moderate steatosis as moderate MASLD etc. Perhaps you should rename the
categories as: Mild steatosis-MASLD, moderate steatosis-MASLD etc
18. Also I suggest to change the Keep category to Stable.
19. Results, page 13, lines 13-17, "suggesting...group". Not fit in the Results section. You could
mention this comment in the Discussion
20. Results, page 13, line  21: Please delete "FAST performed best"
21. Results, Page 14, lines 4-6: "the AUCs of FAST and KNAFLD were the top 2 highest (AUC:
0.87 and 0.84, respectively), and FLI, Liver Fat Equation and Liver Fat Score also performed
well (AUC: 0.83, 0.80 and 0.78, respectively)" - I would suggest to present this results in a Table
that demonstrates the performance of this models to predict statosis progression
22.Results, Page 16, lines 1-4, "This study evaluated eight clinical prediction models for
MASLD using MRI-PDFF, validating them with LSM and histopathological results. KNAFLD
and FAST emerged as superior tools for assessing MASLD severity and progression, making
them valuable assets in managing MASLD patients": Delete or move to the Discussion section
23. Discussion, page 16, lines 6-19: I would suggest this information to be moved in the
Introduction section.
24. Another limitation of the study that needs to be addressed is the lack of an extrinsic validation
cohort to confrm the accuracy of the estimated cut-offs for each score
Please review this paper.
user
Title: Evaluating the Efficacy of 8 Non-invasive Models in Predicting MASLD and Its
Progression: A Prospective Study
Version: 5 Date: 04 Sep 2024
Reviewer's report:
I read with great interest the revised manuscript by Yang et al who aimed to compare the accuracy
of 8 different non invasive models of steatosis in MASLD with MRI-PDFF as the reference
standard as well as the performance of these tests in the prediction of progression of steatosis in
one year time. I have a few comments regarding this paper.
1. The paper needs some English editing. For example:
2. Page 2, "What is already known on this topic", lines: 13, 14: "and early diagnosis and long-
term follow-up using noninvasive methods are needed" - Please rephrase
3. Page 2, :What this study adds", lines 18: Please expand LFC abbreviation
4. As it is written in the abstract (and in main text as well) it is not clear for the readers (especially
not hepatologists) that you are going to compare non-invasive tests of steatosis. Also when you
say progression, you need to clarify that you mean progression of steatosis. You have to indicate
that steatosis this is the main focus of the study.
5. Methods, page 4, line 9: :To investigate the natural course of metabolic associated steatosis
liver disease (MASLD) over a one-year interval, with lifestyle education at enrollment and each
follow-up visit but no pharmacological intervention, except for comorbid conditions requiring
medication (e.g., hypertension, diabetes, hyperlipidemia)" - You need to rephrase the sentence
6. Methods, page 4, line 9: You have already given the expansion of MASLD - please use only
the abbreviation
7. Study design: Please give more details for the design of the study. It is not very clear
how you enrolled patients. Was there a past record of patients with steatosis that you later
enrolled? Did you collect the data prospectively? Which was the time point that patients were
incuded in the study? Was it the day of MRI-PDFF performance? when was the MRI-PDFF
performed in relation to the date of enrollment or in relation to liver biopsy? Give also here the
definitions of degree of steatosis (no steatosis, mild, moderate, severe) according to the MRI-
PDFF measurements
8. Methods, page 6, line 24, "the nonalcoholic fatty liver disease activity score (NAS) were
evaluated": please rephrase
9. Methods, page 6, line 33: Please change MAFLD to MASLD
10. The paragraph of sensitivity analysis should be moved above statistical analysis
11. Tables in general: You have to provide a footnote with all abbreviations used in each table
expanded. Also you have a note that contains statistical analysis performed in the analysis. This
should be deleted and repsrted to the statistical analysis section. Moreover, in the parentheses
of quantitative data you do not explain that this number is the IQR. You have to explain it in the
variables column as you do for (%). For example: Age (years), median (IQR)
12. Results, Page 9, lines 12-17 and 21-25: Delete all data in parentheses as already presented
in Tables
13. Results, Page 9, lines 19-20: Please rephrase as "the equations of the models used in the
study are presented in Suppl Table 1"
14. Considering that 108 patients underwent liver biopsy, please report other information related
to histology apart from MASH presence e.g. fibrosis and METAVIR score, NAS score etc
15. Results, page 10, line 2: Please delete "KNAFLD performed better"
16. Results, page 11, line 14: Please change NAFLD to MASLD
17. I think that it is somewhat misleading to label patients with mild steatosis as mild MASLD,
those with moderate steatosis as moderate MASLD etc. Perhaps you should rename the
categories as: Mild steatosis-MASLD, moderate steatosis-MASLD etc
18. Also I suggest to change the Keep category to Stable.
19. Results, page 13, lines 13-17, "suggesting...group". Not fit in the Results section. You could
mention this comment in the Discussion
20. Results, page 13, line  21: Please delete "FAST performed best"
21. Results, Page 14, lines 4-6: "the AUCs of FAST and KNAFLD were the top 2 highest (AUC:
0.87 and 0.84, respectively), and FLI, Liver Fat Equation and Liver Fat Score also performed
well (AUC: 0.83, 0.80 and 0.78, respectively)" - I would suggest to present this results in a Table
that demonstrates the performance of this models to predict statosis progression
22.Results, Page 16, lines 1-4, "This study evaluated eight clinical prediction models for
MASLD using MRI-PDFF, validating them with LSM and histopathological results. KNAFLD
and FAST emerged as superior tools for assessing MASLD severity and progression, making
them valuable assets in managing MASLD patients": Delete or move to the Discussion section
23. Discussion, page 16, lines 6-19: I would suggest this information to be moved in the
Introduction section.
24. Another limitation of the study that needs to be addressed is the lack of an extrinsic validation
cohort to confrm the accuracy of the estimated cut-offs for each score
assistant