Title: Impact of Sociodemographic Disparities on Sarcopenia, Telomere Length, and Mortality
in Patients with Liver Disease in the US Population
Version: 2 Date: 13 Sep 2024
Reviewer:  Ioannis Andrianopoulos
Reviewer's report:
This is a retrospective study conducted in a large cohort of patients addressing  the relationship
of sarcopenia with telomere length and mortality. Key findings of the study are a prevalence of
sarcopenia of 9.5% among patients with liver disease and an association of the interaction of
telomere and sarcopenia with mortality
Hereby follow my comments.
Methods
The definition of appendicular lean mass (“Sarcopenia was defined using appendicular lean
mass (ALM)less bone mineral content (obtained by DEXA) adjusted for BMI”) is not clear.
Please clarify
Results
1)In the first paragraph of the results section authors provide twice prevalence percentages for
AML please clarify
2) Results in table 1 are not compared statistically (no p values). Their presentation without any
comparison does not offer any valuable information.
3) “all levels of income <45K (except for those whobroadly responded >$20K)”  meaning is
unclear. B reading supplemental table 2 I presume that income is self-reported and that some
subjects reported a non-specific income of >20K while others were more specific. Nevertheless,
it is confusing and probably more of a statistical finding rather a true relationship. How do
authors explain the fact that despite the reduction in the prevalence of sarcopenia as the income
increases a higher income is still a risk factor for sarcopenia (supplemental table 2) ?
4) Figure 2 : see my comment above. The figure shows a reduction in sarcopenia as the income
increases but supplemental table shows that still a higher income (20k-45k) remains a risk factor
for sarcopenia. How do authors explain this paradox?
5)Table 2 the symbol “*” is described in the footnote as explanatory for the sarcopenia
abbreviation. If that is the case why is it next to telomere.
6) “In patients with liver disease, the interaction between telomere length and sarcopenia
was significantly associated with mortality”. How was this assessed? What authors mean by
interaction?
7) A recent systematic meta-analysis has shown that sarcopenia is related to mortality (PMID
34315158).  Short telomeres are associated with sarcopenia. Therefore one would expect that
short telomeres should be associated with mortality. This study did not show   association of
sarcopenia with mortality and showed that long telomeres are associated  also with mortality.
How do authors explain these findings?
8) Table 3 presents two different sizes of telomere (0.75 and 1.25) how were these values
selected, was it arbitrarily?
9) Telomere size decreases with age according to other studies. Is this also the case in this study?
An unadjusted for age association between telomere length and sarcopenia is questionable as
age is a significant confounder.
10) Have the authors considered adjusting for age to assess the association of telomere length
with mortality?
11)  This study does not provide any causal relationship between sarcopenia liver disease,
telomere length and mortality. Have the authors considered performing mediation analysis
looking at the relationship of sarcopenia, telomere length age and mortality?
General comment
Needs extensive language editing especially in terms of typos:  eg needs space between words
(eg Introduction: “ withdeclining”  change to “with declining”).
Title: Impact of Sociodemographic Disparities on Sarcopenia, Telomere Length, and Mortality
in Patients with Liver Disease in the US Population
Version: 2 Date: 13 Sep 2024
Reviewer:  Ioannis Andrianopoulos
Reviewer's report:
This is a retrospective study conducted in a large cohort of patients addressing  the relationship
of sarcopenia with telomere length and mortality. Key findings of the study are a prevalence of
sarcopenia of 9.5% among patients with liver disease and an association of the interaction of
telomere and sarcopenia with mortality
Hereby follow my comments.
Methods
The definition of appendicular lean mass (“Sarcopenia was defined using appendicular lean
mass (ALM)less bone mineral content (obtained by DEXA) adjusted for BMI”) is not clear.
Please clarify
Results
1)In the first paragraph of the results section authors provide twice prevalence percentages for
AML please clarify
2) Results in table 1 are not compared statistically (no p values). Their presentation without any
comparison does not offer any valuable information.
3) “all levels of income <45K (except for those whobroadly responded >$20K)”  meaning is
unclear. B reading supplemental table 2 I presume that income is self-reported and that some
subjects reported a non-specific income of >20K while others were more specific. Nevertheless,
it is confusing and probably more of a statistical finding rather a true relationship. How do
authors explain the fact that despite the reduction in the prevalence of sarcopenia as the income
increases a higher income is still a risk factor for sarcopenia (supplemental table 2) ?
4) Figure 2 : see my comment above. The figure shows a reduction in sarcopenia as the income
increases but supplemental table shows that still a higher income (20k-45k) remains a risk factor
for sarcopenia. How do authors explain this paradox?
5)Table 2 the symbol “*” is described in the footnote as explanatory for the sarcopenia
abbreviation. If that is the case why is it next to telomere.
6) “In patients with liver disease, the interaction between telomere length and sarcopenia
was significantly associated with mortality”. How was this assessed? What authors mean by
interaction?
7) A recent systematic meta-analysis has shown that sarcopenia is related to mortality (PMID
34315158).  Short telomeres are associated with sarcopenia. Therefore one would expect that
short telomeres should be associated with mortality. This study did not show   association of
sarcopenia with mortality and showed that long telomeres are associated  also with mortality.
How do authors explain these findings?
8) Table 3 presents two different sizes of telomere (0.75 and 1.25) how were these values
selected, was it arbitrarily?
9) Telomere size decreases with age according to other studies. Is this also the case in this study?
An unadjusted for age association between telomere length and sarcopenia is questionable as
age is a significant confounder.
10) Have the authors considered adjusting for age to assess the association of telomere length
with mortality?
11)  This study does not provide any causal relationship between sarcopenia liver disease,
telomere length and mortality. Have the authors considered performing mediation analysis
looking at the relationship of sarcopenia, telomere length age and mortality?
General comment
Needs extensive language editing especially in terms of typos:  eg needs space between words
(eg Introduction: “ withdeclining”  change to “with declining”).
Please review this paper.
user
Title: Impact of Sociodemographic Disparities on Sarcopenia, Telomere Length, and Mortality
in Patients with Liver Disease in the US Population
Version: 2 Date: 13 Sep 2024
Reviewer:  Ioannis Andrianopoulos
Reviewer's report:
This is a retrospective study conducted in a large cohort of patients addressing  the relationship
of sarcopenia with telomere length and mortality. Key findings of the study are a prevalence of
sarcopenia of 9.5% among patients with liver disease and an association of the interaction of
telomere and sarcopenia with mortality
Hereby follow my comments.
Methods
The definition of appendicular lean mass (“Sarcopenia was defined using appendicular lean
mass (ALM)less bone mineral content (obtained by DEXA) adjusted for BMI”) is not clear.
Please clarify
Results
1)In the first paragraph of the results section authors provide twice prevalence percentages for
AML please clarify
2) Results in table 1 are not compared statistically (no p values). Their presentation without any
comparison does not offer any valuable information.
3) “all levels of income <45K (except for those whobroadly responded >$20K)”  meaning is
unclear. B reading supplemental table 2 I presume that income is self-reported and that some
subjects reported a non-specific income of >20K while others were more specific. Nevertheless,
it is confusing and probably more of a statistical finding rather a true relationship. How do
authors explain the fact that despite the reduction in the prevalence of sarcopenia as the income
increases a higher income is still a risk factor for sarcopenia (supplemental table 2) ?
4) Figure 2 : see my comment above. The figure shows a reduction in sarcopenia as the income
increases but supplemental table shows that still a higher income (20k-45k) remains a risk factor
for sarcopenia. How do authors explain this paradox?
5)Table 2 the symbol “*” is described in the footnote as explanatory for the sarcopenia
abbreviation. If that is the case why is it next to telomere.
6) “In patients with liver disease, the interaction between telomere length and sarcopenia
was significantly associated with mortality”. How was this assessed? What authors mean by
interaction?
7) A recent systematic meta-analysis has shown that sarcopenia is related to mortality (PMID
34315158).  Short telomeres are associated with sarcopenia. Therefore one would expect that
short telomeres should be associated with mortality. This study did not show   association of
sarcopenia with mortality and showed that long telomeres are associated  also with mortality.
How do authors explain these findings?
8) Table 3 presents two different sizes of telomere (0.75 and 1.25) how were these values
selected, was it arbitrarily?
9) Telomere size decreases with age according to other studies. Is this also the case in this study?
An unadjusted for age association between telomere length and sarcopenia is questionable as
age is a significant confounder.
10) Have the authors considered adjusting for age to assess the association of telomere length
with mortality?
11)  This study does not provide any causal relationship between sarcopenia liver disease,
telomere length and mortality. Have the authors considered performing mediation analysis
looking at the relationship of sarcopenia, telomere length age and mortality?
General comment
Needs extensive language editing especially in terms of typos:  eg needs space between words
(eg Introduction: “ withdeclining”  change to “with declining”).
assistant