Title: Sex- and reproductive status-specific relationships between body composition and non-
alcoholic fatty liver disease
Version: 1 Date: 17 Aug 2023
Reviewer's report:
This study investigated the sex- and menopausal-specific relationships between body
composition (bioelectrical impedance) and the severity of liver steatosis and fibrosis (Fibroscan)
using a sample of 880 participants retrieved from records of patients who attended the
Endocrinology Department of Jiangsu Provincial Hospital of Traditional Chinese Medicine
between January 2022 and October 2022. Please see below my comments on the manuscript:
Major comments:
• Page 6 – Menopause is a major categorization in the manuscript and should be clearly
described. What proportion of women was menopausal status was based on the age cut-point of
49 years? How was menopausal stage characterized in the other participants?
• Page 6 - Is the cutpoint for visceral adiposity  >=100 cm2 validated? Please provide a reference.
• Page 7 – Should the definition of dyslipidaemia be dependent on sex, particularly for HDL
and TG?
• The sample has a very high prevalence of T2D and dylipidaemia, which is not representative
of the normal population. This should be included in the discussion as a limitation.
• Please specify why the covariates in the models were included. For example, why would one
adjust for BMI in a model with percentage body fat? Why was percentage body fat and not fat
mass in kg included in the models? Due to differences in size between men and women, height
should be included in the models.
• For the models, it would be helpful if the body composition variables were normalized (Z-
scores) so the unit change in variables were comparable.
• Page 14 – the authors state “we wonder about the interaction between the three. Does
the relationship between body composition and NAFLD differ by gender or reproductive
status?” To be able to compare if men differ to women and/or premenopausal women differ to
postmenopausal women, an interaction term should be included in the model. If significant sex-
stratified analysis should then be performed.
• A power calculation should be performed to determine and a correct for multiple comparisons
performed. This is particularly relevant for the postmenopausal women (n=108).
• Has the BIA estimate of VFA been validated in this population? Please provide this
information. If the differences in VFA are adjusted for fat mass, do the differences between
pre- and post-menopausal women persist? Further, on page 15 – the authors state “Notably,
visceral obesity was only independently associated with liver steatosis grade in post-menopausal
women. This may be driven by a shift of fat to the viscera in women after menopause”, but in
the manuscipt it is shown that VFA was higher in pre- compared to postmenopausal women.
• There are vast differences in BMI between groups. Do the differences in biochemical
parameters and fibroscan persist when accounting for these differences?
• It is not clear why there is a focus on sarcopenia if the majority of the sample are not of older
age.
Minor comments
• Please improve the grammar. The abstract should be written in the past tense.
• Be consistent with the use of sex and gender. I believe that in the case of this study, sex should
be used as the descriptor.
• Figure 1 – please provide details of what happened between step 1 and step 2 (n=1827)
• Figures 2 and 3 – It is not clear why the body composition is presented in two separate figures,
it should be one.
• Use a more scientific term than “aggravated”.
Title: Sex- and reproductive status-specific relationships between body composition and non-
alcoholic fatty liver disease
Version: 1 Date: 17 Aug 2023
Reviewer's report:
This study investigated the sex- and menopausal-specific relationships between body
composition (bioelectrical impedance) and the severity of liver steatosis and fibrosis (Fibroscan)
using a sample of 880 participants retrieved from records of patients who attended the
Endocrinology Department of Jiangsu Provincial Hospital of Traditional Chinese Medicine
between January 2022 and October 2022. Please see below my comments on the manuscript:
Major comments:
• Page 6 – Menopause is a major categorization in the manuscript and should be clearly
described. What proportion of women was menopausal status was based on the age cut-point of
49 years? How was menopausal stage characterized in the other participants?
• Page 6 - Is the cutpoint for visceral adiposity  >=100 cm2 validated? Please provide a reference.
• Page 7 – Should the definition of dyslipidaemia be dependent on sex, particularly for HDL
and TG?
• The sample has a very high prevalence of T2D and dylipidaemia, which is not representative
of the normal population. This should be included in the discussion as a limitation.
• Please specify why the covariates in the models were included. For example, why would one
adjust for BMI in a model with percentage body fat? Why was percentage body fat and not fat
mass in kg included in the models? Due to differences in size between men and women, height
should be included in the models.
• For the models, it would be helpful if the body composition variables were normalized (Z-
scores) so the unit change in variables were comparable.
• Page 14 – the authors state “we wonder about the interaction between the three. Does
the relationship between body composition and NAFLD differ by gender or reproductive
status?” To be able to compare if men differ to women and/or premenopausal women differ to
postmenopausal women, an interaction term should be included in the model. If significant sex-
stratified analysis should then be performed.
• A power calculation should be performed to determine and a correct for multiple comparisons
performed. This is particularly relevant for the postmenopausal women (n=108).
• Has the BIA estimate of VFA been validated in this population? Please provide this
information. If the differences in VFA are adjusted for fat mass, do the differences between
pre- and post-menopausal women persist? Further, on page 15 – the authors state “Notably,
visceral obesity was only independently associated with liver steatosis grade in post-menopausal
women. This may be driven by a shift of fat to the viscera in women after menopause”, but in
the manuscipt it is shown that VFA was higher in pre- compared to postmenopausal women.
• There are vast differences in BMI between groups. Do the differences in biochemical
parameters and fibroscan persist when accounting for these differences?
• It is not clear why there is a focus on sarcopenia if the majority of the sample are not of older
age.
Minor comments
• Please improve the grammar. The abstract should be written in the past tense.
• Be consistent with the use of sex and gender. I believe that in the case of this study, sex should
be used as the descriptor.
• Figure 1 – please provide details of what happened between step 1 and step 2 (n=1827)
• Figures 2 and 3 – It is not clear why the body composition is presented in two separate figures,
it should be one.
• Use a more scientific term than “aggravated”.
Please review this paper.
user
Title: Sex- and reproductive status-specific relationships between body composition and non-
alcoholic fatty liver disease
Version: 1 Date: 17 Aug 2023
Reviewer's report:
This study investigated the sex- and menopausal-specific relationships between body
composition (bioelectrical impedance) and the severity of liver steatosis and fibrosis (Fibroscan)
using a sample of 880 participants retrieved from records of patients who attended the
Endocrinology Department of Jiangsu Provincial Hospital of Traditional Chinese Medicine
between January 2022 and October 2022. Please see below my comments on the manuscript:
Major comments:
• Page 6 – Menopause is a major categorization in the manuscript and should be clearly
described. What proportion of women was menopausal status was based on the age cut-point of
49 years? How was menopausal stage characterized in the other participants?
• Page 6 - Is the cutpoint for visceral adiposity  >=100 cm2 validated? Please provide a reference.
• Page 7 – Should the definition of dyslipidaemia be dependent on sex, particularly for HDL
and TG?
• The sample has a very high prevalence of T2D and dylipidaemia, which is not representative
of the normal population. This should be included in the discussion as a limitation.
• Please specify why the covariates in the models were included. For example, why would one
adjust for BMI in a model with percentage body fat? Why was percentage body fat and not fat
mass in kg included in the models? Due to differences in size between men and women, height
should be included in the models.
• For the models, it would be helpful if the body composition variables were normalized (Z-
scores) so the unit change in variables were comparable.
• Page 14 – the authors state “we wonder about the interaction between the three. Does
the relationship between body composition and NAFLD differ by gender or reproductive
status?” To be able to compare if men differ to women and/or premenopausal women differ to
postmenopausal women, an interaction term should be included in the model. If significant sex-
stratified analysis should then be performed.
• A power calculation should be performed to determine and a correct for multiple comparisons
performed. This is particularly relevant for the postmenopausal women (n=108).
• Has the BIA estimate of VFA been validated in this population? Please provide this
information. If the differences in VFA are adjusted for fat mass, do the differences between
pre- and post-menopausal women persist? Further, on page 15 – the authors state “Notably,
visceral obesity was only independently associated with liver steatosis grade in post-menopausal
women. This may be driven by a shift of fat to the viscera in women after menopause”, but in
the manuscipt it is shown that VFA was higher in pre- compared to postmenopausal women.
• There are vast differences in BMI between groups. Do the differences in biochemical
parameters and fibroscan persist when accounting for these differences?
• It is not clear why there is a focus on sarcopenia if the majority of the sample are not of older
age.
Minor comments
• Please improve the grammar. The abstract should be written in the past tense.
• Be consistent with the use of sex and gender. I believe that in the case of this study, sex should
be used as the descriptor.
• Figure 1 – please provide details of what happened between step 1 and step 2 (n=1827)
• Figures 2 and 3 – It is not clear why the body composition is presented in two separate figures,
it should be one.
• Use a more scientific term than “aggravated”.
assistant