Reviewer ’s report  
 
Title: Low Vitamin D Level Was AssociatedWith Metabolic Syndro me And High Leptin Level 
In Subjects With Nonalcoholic Fatty Liver Disease: A Community -based Study  
 
Version: 1 Date: 02 Nov 2018  
 
Reviewer: Anam Khan  
 
Reviewer's report:  
 
In this cross -sectional study, Chen and colleagues examine the association of serum vitamin D 
levels and risk of metabolic syndrome and hepatic steatosis severity.  
 
The manuscript has a few limitations. The authors use abdominal ultrasound to determine the 
severity of hepat ic steatosis. On page 12, line 206 -208, the authors state "The degree of fatty 
liver disease was graded as normal (absent), mild, moderate or severe, on the basis of the intense 
reflection level of echogenicity". Liver biopsy is currently the most reliable  approach for 
identifying for the presence of steatohepatitis and fibrosis in patients with NAFLD. Imaging tests 
such as ultrasound do not reliably reflect the spectrum of liver histology in patients with 
NAFLD. Imaging such as with magnetic resonance elas tography or transient elastography are 
validated noninvasive imaging modalities for assessment of advanced fibrosis in patients with 
NAFLD which were not used by the study authors.  
 
The authors do calculate the NAFLD fibrosis score which is a validated cl inical decision aid to 
predict likelihood of advanced fibrosis. However according to the authors, most subjects with 
NAFLD did not have an advanced fibrosis status. On page 13, line 281, the authors state "77% of 
subjects present a NAFLD fibrosis score < -1.455, indicating a low degree of fibrosis (F0 -2). 
Only 6 subjects with a NAFLD fibrosis score >0.674 (high degree of fibrosis, F3 -4) were 
identified in this study". Hence, the authors could not draw any conclusions regarding an 
association between vitamin D levels and fibrosis in subjects with NAFLD.  
 
Hence, this reviewer recommends that the association of vitamin D with severity of NAFLD be 
removed from the primary aim if using abdominal ultrasound alone to determine severity of 
NAFLD. The primary aim sho uld be limited to determine the association of vitamin D with 
NAFLD.  
 
The authors have mentioned that one of the strengths of their study was that they measured the 
serum levels of inflammatory cytokines e.g. adiponectin, leptin, CRP and TNF -alpha. The 
secondary aim of the study should be explicitly stated to reflect that the association between 
serum vitamin D levels and levels of adiponectin, leptin, CRP and TNF -alpha was to be 
determined.  
 
Overall, the authors have done a good job of demonstrating that s erum vitamin D levels are 
associated with metabolic syndrome independently of confounders such as obesity and NAFLD 
status.  
 
The authors should include that one of the limitations of their study was the inclusion of a 
majority of patients with NAFLD witho ut advanced fibrosis based on NAFLD fibrosis scores. 
This could explain why no association was found between serum vitamin D levels and NAFLD.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequatel y supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, p lease specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this  manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied f or patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the a uthors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer  review policy of the journal  
Reviewer ’s report  
 
Title: Low Vitamin D Level Was AssociatedWith Metabolic Syndro me And High Leptin Level 
In Subjects With Nonalcoholic Fatty Liver Disease: A Community -based Study  
 
Version: 1 Date: 02 Nov 2018  
 
Reviewer: Anam Khan  
 
Reviewer's report:  
 
In this cross -sectional study, Chen and colleagues examine the association of serum vitamin D 
levels and risk of metabolic syndrome and hepatic steatosis severity.  
 
The manuscript has a few limitations. The authors use abdominal ultrasound to determine the 
severity of hepat ic steatosis. On page 12, line 206 -208, the authors state "The degree of fatty 
liver disease was graded as normal (absent), mild, moderate or severe, on the basis of the intense 
reflection level of echogenicity". Liver biopsy is currently the most reliable  approach for 
identifying for the presence of steatohepatitis and fibrosis in patients with NAFLD. Imaging tests 
such as ultrasound do not reliably reflect the spectrum of liver histology in patients with 
NAFLD. Imaging such as with magnetic resonance elas tography or transient elastography are 
validated noninvasive imaging modalities for assessment of advanced fibrosis in patients with 
NAFLD which were not used by the study authors.  
 
The authors do calculate the NAFLD fibrosis score which is a validated cl inical decision aid to 
predict likelihood of advanced fibrosis. However according to the authors, most subjects with 
NAFLD did not have an advanced fibrosis status. On page 13, line 281, the authors state "77% of 
subjects present a NAFLD fibrosis score < -1.455, indicating a low degree of fibrosis (F0 -2). 
Only 6 subjects with a NAFLD fibrosis score >0.674 (high degree of fibrosis, F3 -4) were 
identified in this study". Hence, the authors could not draw any conclusions regarding an 
association between vitamin D levels and fibrosis in subjects with NAFLD.  
 
Hence, this reviewer recommends that the association of vitamin D with severity of NAFLD be 
removed from the primary aim if using abdominal ultrasound alone to determine severity of 
NAFLD. The primary aim sho uld be limited to determine the association of vitamin D with 
NAFLD.  
 
The authors have mentioned that one of the strengths of their study was that they measured the 
serum levels of inflammatory cytokines e.g. adiponectin, leptin, CRP and TNF -alpha. The 
secondary aim of the study should be explicitly stated to reflect that the association between 
serum vitamin D levels and levels of adiponectin, leptin, CRP and TNF -alpha was to be 
determined.  
 
Overall, the authors have done a good job of demonstrating that s erum vitamin D levels are 
associated with metabolic syndrome independently of confounders such as obesity and NAFLD 
status.  
 
The authors should include that one of the limitations of their study was the inclusion of a 
majority of patients with NAFLD witho ut advanced fibrosis based on NAFLD fibrosis scores. 
This could explain why no association was found between serum vitamin D levels and NAFLD.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequatel y supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, p lease specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this  manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied f or patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the a uthors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer  review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Low Vitamin D Level Was AssociatedWith Metabolic Syndro me And High Leptin Level 
In Subjects With Nonalcoholic Fatty Liver Disease: A Community -based Study  
 
Version: 1 Date: 02 Nov 2018  
 
Reviewer: Anam Khan  
 
Reviewer's report:  
 
In this cross -sectional study, Chen and colleagues examine the association of serum vitamin D 
levels and risk of metabolic syndrome and hepatic steatosis severity.  
 
The manuscript has a few limitations. The authors use abdominal ultrasound to determine the 
severity of hepat ic steatosis. On page 12, line 206 -208, the authors state "The degree of fatty 
liver disease was graded as normal (absent), mild, moderate or severe, on the basis of the intense 
reflection level of echogenicity". Liver biopsy is currently the most reliable  approach for 
identifying for the presence of steatohepatitis and fibrosis in patients with NAFLD. Imaging tests 
such as ultrasound do not reliably reflect the spectrum of liver histology in patients with 
NAFLD. Imaging such as with magnetic resonance elas tography or transient elastography are 
validated noninvasive imaging modalities for assessment of advanced fibrosis in patients with 
NAFLD which were not used by the study authors.  
 
The authors do calculate the NAFLD fibrosis score which is a validated cl inical decision aid to 
predict likelihood of advanced fibrosis. However according to the authors, most subjects with 
NAFLD did not have an advanced fibrosis status. On page 13, line 281, the authors state "77% of 
subjects present a NAFLD fibrosis score < -1.455, indicating a low degree of fibrosis (F0 -2). 
Only 6 subjects with a NAFLD fibrosis score >0.674 (high degree of fibrosis, F3 -4) were 
identified in this study". Hence, the authors could not draw any conclusions regarding an 
association between vitamin D levels and fibrosis in subjects with NAFLD.  
 
Hence, this reviewer recommends that the association of vitamin D with severity of NAFLD be 
removed from the primary aim if using abdominal ultrasound alone to determine severity of 
NAFLD. The primary aim sho uld be limited to determine the association of vitamin D with 
NAFLD.  
 
The authors have mentioned that one of the strengths of their study was that they measured the 
serum levels of inflammatory cytokines e.g. adiponectin, leptin, CRP and TNF -alpha. The 
secondary aim of the study should be explicitly stated to reflect that the association between 
serum vitamin D levels and levels of adiponectin, leptin, CRP and TNF -alpha was to be 
determined.  
 
Overall, the authors have done a good job of demonstrating that s erum vitamin D levels are 
associated with metabolic syndrome independently of confounders such as obesity and NAFLD 
status.  
 
The authors should include that one of the limitations of their study was the inclusion of a 
majority of patients with NAFLD witho ut advanced fibrosis based on NAFLD fibrosis scores. 
This could explain why no association was found between serum vitamin D levels and NAFLD.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequatel y supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, p lease specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this  manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied f or patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the a uthors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer  review policy of the journal  
assistant