Reviewer ’s report  
 
Title:  Cholesterol esterification in plasma as a biomarker for liver function and prediction of 
mortality  
 
Version: 0 Date: 13 Feb 2017 
 
Reviewer:  Hirokazu  Takahashi  
 
Reviewer’s report:  
 
BMGE -D-16-00482  
 
Authors reported tha t cholesterol esterification (CE) fraction is a potential biomarker for liver 
synthesis and able to predict the mortality of the patients with liver cirrhosis. This manuscript is 
well organized and findings are interesting whereas authors should access sev eral points below.  
 
 
Major Comments  
 
1. According to the description in this manuscript, this is the first time -measurement and 
evaluation of CE fraction in the patients with liver cirrhosis. Therefore, authors should clarify the 
details of clinical signif icance of CE more including sexual difference and aging effect. Data 
about plasma vs. serum should be visualized in supplementary figure.  
 
2. Relationship between CE and total cholesterol has not been clear in this manuscript. 
Also, if the total cholesterol  concentration works to predict the mortality, it would be much 
easier procedure.      
 
3. Authors emphasized that PT -INR has limitation in the patients taking anticoagulants. 
However, this reviewer thinks more patients take antidyslipidemic agents which co uld affect CE 
and total cholesterol level. Authors should evaluate the effect of antidyslipidemic agents on their 
results.  
 
4. Mortality of liver cirrhosis is generally caused by liver failure, hepatocellular carcinoma 
and others. Because CE mainly depends on the liver synthesis, the authors should test if CE also 
could predict the mortality of only hepatocellular carcinoma. Authors also should mention the 
treatment of cirrhosis and hepatocellular carcinoma during the observation period.            
 
 
Minor comments  
 
1. Result (Page 10, line 178 -). This part is redundant and already mentioned in the Patients 
and Method.  
 
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.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additiona l statistical review is recommended, please 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 futur e? 
 
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 for patents relating to the content of the m anuscript?  
 
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 authors  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, w hich will not be published . 
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title:  Cholesterol esterification in plasma as a biomarker for liver function and prediction of 
mortality  
 
Version: 0 Date: 13 Feb 2017 
 
Reviewer:  Hirokazu  Takahashi  
 
Reviewer’s report:  
 
BMGE -D-16-00482  
 
Authors reported tha t cholesterol esterification (CE) fraction is a potential biomarker for liver 
synthesis and able to predict the mortality of the patients with liver cirrhosis. This manuscript is 
well organized and findings are interesting whereas authors should access sev eral points below.  
 
 
Major Comments  
 
1. According to the description in this manuscript, this is the first time -measurement and 
evaluation of CE fraction in the patients with liver cirrhosis. Therefore, authors should clarify the 
details of clinical signif icance of CE more including sexual difference and aging effect. Data 
about plasma vs. serum should be visualized in supplementary figure.  
 
2. Relationship between CE and total cholesterol has not been clear in this manuscript. 
Also, if the total cholesterol  concentration works to predict the mortality, it would be much 
easier procedure.      
 
3. Authors emphasized that PT -INR has limitation in the patients taking anticoagulants. 
However, this reviewer thinks more patients take antidyslipidemic agents which co uld affect CE 
and total cholesterol level. Authors should evaluate the effect of antidyslipidemic agents on their 
results.  
 
4. Mortality of liver cirrhosis is generally caused by liver failure, hepatocellular carcinoma 
and others. Because CE mainly depends on the liver synthesis, the authors should test if CE also 
could predict the mortality of only hepatocellular carcinoma. Authors also should mention the 
treatment of cirrhosis and hepatocellular carcinoma during the observation period.            
 
 
Minor comments  
 
1. Result (Page 10, line 178 -). This part is redundant and already mentioned in the Patients 
and Method.  
 
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.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additiona l statistical review is recommended, please 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 futur e? 
 
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 for patents relating to the content of the m anuscript?  
 
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 authors  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, w hich will not be published . 
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title:  Cholesterol esterification in plasma as a biomarker for liver function and prediction of 
mortality  
 
Version: 0 Date: 13 Feb 2017 
 
Reviewer:  Hirokazu  Takahashi  
 
Reviewer’s report:  
 
BMGE -D-16-00482  
 
Authors reported tha t cholesterol esterification (CE) fraction is a potential biomarker for liver 
synthesis and able to predict the mortality of the patients with liver cirrhosis. This manuscript is 
well organized and findings are interesting whereas authors should access sev eral points below.  
 
 
Major Comments  
 
1. According to the description in this manuscript, this is the first time -measurement and 
evaluation of CE fraction in the patients with liver cirrhosis. Therefore, authors should clarify the 
details of clinical signif icance of CE more including sexual difference and aging effect. Data 
about plasma vs. serum should be visualized in supplementary figure.  
 
2. Relationship between CE and total cholesterol has not been clear in this manuscript. 
Also, if the total cholesterol  concentration works to predict the mortality, it would be much 
easier procedure.      
 
3. Authors emphasized that PT -INR has limitation in the patients taking anticoagulants. 
However, this reviewer thinks more patients take antidyslipidemic agents which co uld affect CE 
and total cholesterol level. Authors should evaluate the effect of antidyslipidemic agents on their 
results.  
 
4. Mortality of liver cirrhosis is generally caused by liver failure, hepatocellular carcinoma 
and others. Because CE mainly depends on the liver synthesis, the authors should test if CE also 
could predict the mortality of only hepatocellular carcinoma. Authors also should mention the 
treatment of cirrhosis and hepatocellular carcinoma during the observation period.            
 
 
Minor comments  
 
1. Result (Page 10, line 178 -). This part is redundant and already mentioned in the Patients 
and Method.  
 
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.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additiona l statistical review is recommended, please 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 futur e? 
 
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 for patents relating to the content of the m anuscript?  
 
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 authors  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, w hich will not be published . 
 
I agree to the open peer review policy of the journal  
assistant