Title: U-shaped association of the stress hyperglycemia ratio for all-cause and cardiovascular
mortality in patients with NAFLD: results from the NHANES database prospective cohort study
Version: 0 Date: 22 May 2025
Reviewer:  Alireza Ramandi
Reviewer's report:
Line 62: please use recent GBD studies / epidemiologic original studies, instead of meta-analyses
(references 1 and 2) in reporting prevalence of fatty liver disease. Your reference number 3 is
a very appreciated paper in the field, but it would be more robust if you could provide a newer
publication along with it.
Line 69: “in-depth understanding of the pathogenesis of NAFLD” the word pathogenesis implies
understanding the underlying molecular pathway that leads to NAFLD, whereas studying cohort
fails to provide sufficient causality for that matter. Please revise the word pathogenesis into
predictive factors, or associations, or similar words.
Line 73: please change the word “admission” due to inaccuracy.
Line 79: the reference number 12 discusses if SHR is a better mortality biomarker in acute
COVID-19 patients. While the major focus of the article is on random blood glucose in
comparison to SHR, it mentions briefly that HBA1C did not show any significant association
with mortality, but SHR did. Nevertheless, this is only in COVID-19 patients, the power of the
study seems to be insufficient, and the setting of the disease is acute. There are no justifications
for your sentence. Please revise your sentence, replace your cited reference, and provide a
justification how an acute marker could help in prediciting mortality in a chronic disease.
Methods/Discussion-limitations: please either justify why you have not included PNPLA3 gene
polymorphism within your covariates in the method section, or in discussion section mention
your limitation of not having PNPLA3 data available. PNPLA3 is the most important gene
variation that has been associated with NAFLD and hepatosteatosis. The importance of this gene
is that it has approximately same prevalence as the NAFLD itself (~30% worldwide) and it is
within a complex pathogenesis pathway that leads to NAFLD. A suitable article to be added
for your references in either method section (justifying lack of PNPLA3 data) and/or discssion
limitation section (Mentioning this phenomenon as a major limitation to your study) would
be: DOI: 10.1111/liv.70091 which has extensively described the role of PNPLA3 and modeled
it, along with a suitable history of PNPLA3 discovery. Please revise your limitation section
by adding this important covariate that has not been included in your study, and cite suitable
references.
Methods: please justify and provide your ad-hoc statistical analysis that has lead you find the
“non-linear” association. A cox survival analysis or a regression cannot provide that data, unless
provided with sufficient ad-hoc tests.
Methods: please provide your Kaplan Meier curve.
Title: U-shaped association of the stress hyperglycemia ratio for all-cause and cardiovascular
mortality in patients with NAFLD: results from the NHANES database prospective cohort study
Version: 0 Date: 22 May 2025
Reviewer:  Alireza Ramandi
Reviewer's report:
Line 62: please use recent GBD studies / epidemiologic original studies, instead of meta-analyses
(references 1 and 2) in reporting prevalence of fatty liver disease. Your reference number 3 is
a very appreciated paper in the field, but it would be more robust if you could provide a newer
publication along with it.
Line 69: “in-depth understanding of the pathogenesis of NAFLD” the word pathogenesis implies
understanding the underlying molecular pathway that leads to NAFLD, whereas studying cohort
fails to provide sufficient causality for that matter. Please revise the word pathogenesis into
predictive factors, or associations, or similar words.
Line 73: please change the word “admission” due to inaccuracy.
Line 79: the reference number 12 discusses if SHR is a better mortality biomarker in acute
COVID-19 patients. While the major focus of the article is on random blood glucose in
comparison to SHR, it mentions briefly that HBA1C did not show any significant association
with mortality, but SHR did. Nevertheless, this is only in COVID-19 patients, the power of the
study seems to be insufficient, and the setting of the disease is acute. There are no justifications
for your sentence. Please revise your sentence, replace your cited reference, and provide a
justification how an acute marker could help in prediciting mortality in a chronic disease.
Methods/Discussion-limitations: please either justify why you have not included PNPLA3 gene
polymorphism within your covariates in the method section, or in discussion section mention
your limitation of not having PNPLA3 data available. PNPLA3 is the most important gene
variation that has been associated with NAFLD and hepatosteatosis. The importance of this gene
is that it has approximately same prevalence as the NAFLD itself (~30% worldwide) and it is
within a complex pathogenesis pathway that leads to NAFLD. A suitable article to be added
for your references in either method section (justifying lack of PNPLA3 data) and/or discssion
limitation section (Mentioning this phenomenon as a major limitation to your study) would
be: DOI: 10.1111/liv.70091 which has extensively described the role of PNPLA3 and modeled
it, along with a suitable history of PNPLA3 discovery. Please revise your limitation section
by adding this important covariate that has not been included in your study, and cite suitable
references.
Methods: please justify and provide your ad-hoc statistical analysis that has lead you find the
“non-linear” association. A cox survival analysis or a regression cannot provide that data, unless
provided with sufficient ad-hoc tests.
Methods: please provide your Kaplan Meier curve.
Please review this paper.
user
Title: U-shaped association of the stress hyperglycemia ratio for all-cause and cardiovascular
mortality in patients with NAFLD: results from the NHANES database prospective cohort study
Version: 0 Date: 22 May 2025
Reviewer:  Alireza Ramandi
Reviewer's report:
Line 62: please use recent GBD studies / epidemiologic original studies, instead of meta-analyses
(references 1 and 2) in reporting prevalence of fatty liver disease. Your reference number 3 is
a very appreciated paper in the field, but it would be more robust if you could provide a newer
publication along with it.
Line 69: “in-depth understanding of the pathogenesis of NAFLD” the word pathogenesis implies
understanding the underlying molecular pathway that leads to NAFLD, whereas studying cohort
fails to provide sufficient causality for that matter. Please revise the word pathogenesis into
predictive factors, or associations, or similar words.
Line 73: please change the word “admission” due to inaccuracy.
Line 79: the reference number 12 discusses if SHR is a better mortality biomarker in acute
COVID-19 patients. While the major focus of the article is on random blood glucose in
comparison to SHR, it mentions briefly that HBA1C did not show any significant association
with mortality, but SHR did. Nevertheless, this is only in COVID-19 patients, the power of the
study seems to be insufficient, and the setting of the disease is acute. There are no justifications
for your sentence. Please revise your sentence, replace your cited reference, and provide a
justification how an acute marker could help in prediciting mortality in a chronic disease.
Methods/Discussion-limitations: please either justify why you have not included PNPLA3 gene
polymorphism within your covariates in the method section, or in discussion section mention
your limitation of not having PNPLA3 data available. PNPLA3 is the most important gene
variation that has been associated with NAFLD and hepatosteatosis. The importance of this gene
is that it has approximately same prevalence as the NAFLD itself (~30% worldwide) and it is
within a complex pathogenesis pathway that leads to NAFLD. A suitable article to be added
for your references in either method section (justifying lack of PNPLA3 data) and/or discssion
limitation section (Mentioning this phenomenon as a major limitation to your study) would
be: DOI: 10.1111/liv.70091 which has extensively described the role of PNPLA3 and modeled
it, along with a suitable history of PNPLA3 discovery. Please revise your limitation section
by adding this important covariate that has not been included in your study, and cite suitable
references.
Methods: please justify and provide your ad-hoc statistical analysis that has lead you find the
“non-linear” association. A cox survival analysis or a regression cannot provide that data, unless
provided with sufficient ad-hoc tests.
Methods: please provide your Kaplan Meier curve.
assistant