Title: The relationship between Sarcopenia and Metabolic dysfunction-associated fatty liver
disease among the young and middle-aged populations
Version: 0 Date: 05 Feb 2024
Reviewer:  Laurens A. van Kleef
Reviewer's report:
We had the honour to review the manuscript on the associations between SLD and fibrosis with
sarcopenia among younger populations. Although the analyses were extensive, some questions
remain on whether these analyses were performed or what the results actually mean for further
research or clinical practice.
Major revisions
1. Steatotic liver disease has been the newly introduced definition since June 2023 and debate on
whether it is NAFLD or MAFLD is no longer relevant. Therefore the discussion on differences
between NAFLD and MAFLD should be removed from the manuscript and I would recommend
the authors to update the analysis towards MASLD (slightly different from MAFLD).
2. I do not understand how the sample size was reached. To the best of my knowledge, only
+/- 8.000 participants are included in the 2017-2018 dataset. And not over 9.000 as presented
in the flowchart.
3. The ordinal logistic regression is difficult to understand and assumes a similar effect size
between phenotype steps. I think it is better to report the effect size for (1) mild and (2) moderate/
severe steatosis compared to non-MASLD
4. Any thoughts on why the association between MAFLD (and fibrosis) with sarcopenia
completely disappears in subgroup analysis focussing on BMI < 30 and BMI > 30? Would this
implicate that every association reported in the study can be explained by BMI? I miss discussing
the potential effect of BMI on both MASLD and sarcopenia (especially since the definition uses
BMI).
5. Please provide a DAG indicating why some variables were tought to be mediators while others
only confounders.
6. Since age is an important confouder an not totally accounted for by simply adding age as a
linear confounder, did the authors consider including Age^2 to the models as well?
7. The non-linear relationship is not well explained in the discussion. What is the consequence?
What should we further adjust in additional studies? Or does it not have any consequences since
it is only non-linear in the extremes?
Minor revisions
1. Please check spelling and grammar, for example line 60 an other lines are not very simple
to understand
2. Please use sex instead of gender (as sex is how we are born and gender is how we feel)
3. In the conclusion, avoid the terms develop and progress. You may change it into MAFLD
prevalance and severity for example. Similar to line 292: please avoid develop, it is not clear
whether MAFLD results in sarcopenia or vice versa. And similar to line 287 only associations
were reported no causality is tested
4. Liver ultrasound as mentioned in line 315 is not used in the NHANES. Steatosis was based
on CAP and fibrosis on TE.
5. Please add a sensitivity analysis in which liver stiffness 8.0 kPa is used instead of the 6 as in
this study. 8.0 kPa is a more common cut-off in the general population.
6. Consider presenting the results in the figures on a log transformed scale instead of a normal
scale to make it more visually pleasing.
Title: The relationship between Sarcopenia and Metabolic dysfunction-associated fatty liver
disease among the young and middle-aged populations
Version: 0 Date: 05 Feb 2024
Reviewer:  Laurens A. van Kleef
Reviewer's report:
We had the honour to review the manuscript on the associations between SLD and fibrosis with
sarcopenia among younger populations. Although the analyses were extensive, some questions
remain on whether these analyses were performed or what the results actually mean for further
research or clinical practice.
Major revisions
1. Steatotic liver disease has been the newly introduced definition since June 2023 and debate on
whether it is NAFLD or MAFLD is no longer relevant. Therefore the discussion on differences
between NAFLD and MAFLD should be removed from the manuscript and I would recommend
the authors to update the analysis towards MASLD (slightly different from MAFLD).
2. I do not understand how the sample size was reached. To the best of my knowledge, only
+/- 8.000 participants are included in the 2017-2018 dataset. And not over 9.000 as presented
in the flowchart.
3. The ordinal logistic regression is difficult to understand and assumes a similar effect size
between phenotype steps. I think it is better to report the effect size for (1) mild and (2) moderate/
severe steatosis compared to non-MASLD
4. Any thoughts on why the association between MAFLD (and fibrosis) with sarcopenia
completely disappears in subgroup analysis focussing on BMI < 30 and BMI > 30? Would this
implicate that every association reported in the study can be explained by BMI? I miss discussing
the potential effect of BMI on both MASLD and sarcopenia (especially since the definition uses
BMI).
5. Please provide a DAG indicating why some variables were tought to be mediators while others
only confounders.
6. Since age is an important confouder an not totally accounted for by simply adding age as a
linear confounder, did the authors consider including Age^2 to the models as well?
7. The non-linear relationship is not well explained in the discussion. What is the consequence?
What should we further adjust in additional studies? Or does it not have any consequences since
it is only non-linear in the extremes?
Minor revisions
1. Please check spelling and grammar, for example line 60 an other lines are not very simple
to understand
2. Please use sex instead of gender (as sex is how we are born and gender is how we feel)
3. In the conclusion, avoid the terms develop and progress. You may change it into MAFLD
prevalance and severity for example. Similar to line 292: please avoid develop, it is not clear
whether MAFLD results in sarcopenia or vice versa. And similar to line 287 only associations
were reported no causality is tested
4. Liver ultrasound as mentioned in line 315 is not used in the NHANES. Steatosis was based
on CAP and fibrosis on TE.
5. Please add a sensitivity analysis in which liver stiffness 8.0 kPa is used instead of the 6 as in
this study. 8.0 kPa is a more common cut-off in the general population.
6. Consider presenting the results in the figures on a log transformed scale instead of a normal
scale to make it more visually pleasing.
Please review this paper.
user
Title: The relationship between Sarcopenia and Metabolic dysfunction-associated fatty liver
disease among the young and middle-aged populations
Version: 0 Date: 05 Feb 2024
Reviewer:  Laurens A. van Kleef
Reviewer's report:
We had the honour to review the manuscript on the associations between SLD and fibrosis with
sarcopenia among younger populations. Although the analyses were extensive, some questions
remain on whether these analyses were performed or what the results actually mean for further
research or clinical practice.
Major revisions
1. Steatotic liver disease has been the newly introduced definition since June 2023 and debate on
whether it is NAFLD or MAFLD is no longer relevant. Therefore the discussion on differences
between NAFLD and MAFLD should be removed from the manuscript and I would recommend
the authors to update the analysis towards MASLD (slightly different from MAFLD).
2. I do not understand how the sample size was reached. To the best of my knowledge, only
+/- 8.000 participants are included in the 2017-2018 dataset. And not over 9.000 as presented
in the flowchart.
3. The ordinal logistic regression is difficult to understand and assumes a similar effect size
between phenotype steps. I think it is better to report the effect size for (1) mild and (2) moderate/
severe steatosis compared to non-MASLD
4. Any thoughts on why the association between MAFLD (and fibrosis) with sarcopenia
completely disappears in subgroup analysis focussing on BMI < 30 and BMI > 30? Would this
implicate that every association reported in the study can be explained by BMI? I miss discussing
the potential effect of BMI on both MASLD and sarcopenia (especially since the definition uses
BMI).
5. Please provide a DAG indicating why some variables were tought to be mediators while others
only confounders.
6. Since age is an important confouder an not totally accounted for by simply adding age as a
linear confounder, did the authors consider including Age^2 to the models as well?
7. The non-linear relationship is not well explained in the discussion. What is the consequence?
What should we further adjust in additional studies? Or does it not have any consequences since
it is only non-linear in the extremes?
Minor revisions
1. Please check spelling and grammar, for example line 60 an other lines are not very simple
to understand
2. Please use sex instead of gender (as sex is how we are born and gender is how we feel)
3. In the conclusion, avoid the terms develop and progress. You may change it into MAFLD
prevalance and severity for example. Similar to line 292: please avoid develop, it is not clear
whether MAFLD results in sarcopenia or vice versa. And similar to line 287 only associations
were reported no causality is tested
4. Liver ultrasound as mentioned in line 315 is not used in the NHANES. Steatosis was based
on CAP and fibrosis on TE.
5. Please add a sensitivity analysis in which liver stiffness 8.0 kPa is used instead of the 6 as in
this study. 8.0 kPa is a more common cut-off in the general population.
6. Consider presenting the results in the figures on a log transformed scale instead of a normal
scale to make it more visually pleasing.
assistant