Reviewer ’s report  
 
Title: Serum amyloid A is a better predictive biomarker of mucosal healing than C -reactive 
protein in ulcerative colitis in clinica l remission  
 
Version: 0 Date: 04 Aug 2019  
 
Reviewer: Shunji Ishihara  
 
Reviewer's report:  
 
This study was performed to evaluate whether SAA is a better serum biomarker than CRP for 
predicting mucos al healing in UC patients in clinical remission. In examinations of findings of a 
total of 199 colonoscopy procedures conducted in 108 patients, the authors found that SAA had a 
stronger correlation with mucosal inflammation as compared to CRP, and also sh owed excellent 
sensitivity and specificity with significant statistical significance. Although the focus of this 
study is interesting, there are some critical issues that must be addressed. Following are this 
reviewer's comments for the authors.  
 
 
Comments  
 
1. The authors did not evaluate the utility of SAA in association with several important 
clinical factors, including disease extent (Montreal classification) and therapeutic 
regimen. In particular, medications such as corticosteroids and biologics can infl uence 
the usefulness of SAA and CRP for monitoring mucosal activity.  
 
2. As noted by the authors, SAA is produced by the liver (hepatocytes) during an acute 
phase of inflammation and pro -inflammatory cytokines, including interleukin (IL) -6, 
play essential r oles in its production. Although the biological characteristics of SAA are 
similar to those of CRP, the authors concluded that SAA has better utility for 
evaluating mucosal activity in UC patients as compared to CRP. The reasons and/or 
involved mechanisms related to this issue should be clearly discussed.  
 
3. Did the authors examine the clinical backgrounds of UC patients in whom a high 
effectiveness of SAA as compared to CRP was shown? Such analysis may be useful for 
making a proper choice between CRP and S AA in clinical settings.  
 
4. A recently published study (Dig Liver Dis. 2018 Jun;50(6):553 -558. 2018) revealed 
that SAA level was correlated with endoscopic findings in patients with Crohn's disease 
(CD). Those authors concluded that SAA is a possible bioma rker for evaluating 
mucosal healing. It would be good for the present authors to discuss the clinical utility 
of SAA in UC as compared to CD patients.  
 
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 th e necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
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 asses s any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this man uscript  
 
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 f ive years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2.  Do you  hold any stocks or shares in an organisation t hat 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 for 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 understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the webs ite 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 nam ed report can be in cluded 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: Serum amyloid A is a better predictive biomarker of mucosal healing than C -reactive 
protein in ulcerative colitis in clinica l remission  
 
Version: 0 Date: 04 Aug 2019  
 
Reviewer: Shunji Ishihara  
 
Reviewer's report:  
 
This study was performed to evaluate whether SAA is a better serum biomarker than CRP for 
predicting mucos al healing in UC patients in clinical remission. In examinations of findings of a 
total of 199 colonoscopy procedures conducted in 108 patients, the authors found that SAA had a 
stronger correlation with mucosal inflammation as compared to CRP, and also sh owed excellent 
sensitivity and specificity with significant statistical significance. Although the focus of this 
study is interesting, there are some critical issues that must be addressed. Following are this 
reviewer's comments for the authors.  
 
 
Comments  
 
1. The authors did not evaluate the utility of SAA in association with several important 
clinical factors, including disease extent (Montreal classification) and therapeutic 
regimen. In particular, medications such as corticosteroids and biologics can infl uence 
the usefulness of SAA and CRP for monitoring mucosal activity.  
 
2. As noted by the authors, SAA is produced by the liver (hepatocytes) during an acute 
phase of inflammation and pro -inflammatory cytokines, including interleukin (IL) -6, 
play essential r oles in its production. Although the biological characteristics of SAA are 
similar to those of CRP, the authors concluded that SAA has better utility for 
evaluating mucosal activity in UC patients as compared to CRP. The reasons and/or 
involved mechanisms related to this issue should be clearly discussed.  
 
3. Did the authors examine the clinical backgrounds of UC patients in whom a high 
effectiveness of SAA as compared to CRP was shown? Such analysis may be useful for 
making a proper choice between CRP and S AA in clinical settings.  
 
4. A recently published study (Dig Liver Dis. 2018 Jun;50(6):553 -558. 2018) revealed 
that SAA level was correlated with endoscopic findings in patients with Crohn's disease 
(CD). Those authors concluded that SAA is a possible bioma rker for evaluating 
mucosal healing. It would be good for the present authors to discuss the clinical utility 
of SAA in UC as compared to CD patients.  
 
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 th e necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
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 asses s any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this man uscript  
 
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 f ive years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2.  Do you  hold any stocks or shares in an organisation t hat 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 for 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 understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the webs ite 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 nam ed report can be in cluded 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: Serum amyloid A is a better predictive biomarker of mucosal healing than C -reactive 
protein in ulcerative colitis in clinica l remission  
 
Version: 0 Date: 04 Aug 2019  
 
Reviewer: Shunji Ishihara  
 
Reviewer's report:  
 
This study was performed to evaluate whether SAA is a better serum biomarker than CRP for 
predicting mucos al healing in UC patients in clinical remission. In examinations of findings of a 
total of 199 colonoscopy procedures conducted in 108 patients, the authors found that SAA had a 
stronger correlation with mucosal inflammation as compared to CRP, and also sh owed excellent 
sensitivity and specificity with significant statistical significance. Although the focus of this 
study is interesting, there are some critical issues that must be addressed. Following are this 
reviewer's comments for the authors.  
 
 
Comments  
 
1. The authors did not evaluate the utility of SAA in association with several important 
clinical factors, including disease extent (Montreal classification) and therapeutic 
regimen. In particular, medications such as corticosteroids and biologics can infl uence 
the usefulness of SAA and CRP for monitoring mucosal activity.  
 
2. As noted by the authors, SAA is produced by the liver (hepatocytes) during an acute 
phase of inflammation and pro -inflammatory cytokines, including interleukin (IL) -6, 
play essential r oles in its production. Although the biological characteristics of SAA are 
similar to those of CRP, the authors concluded that SAA has better utility for 
evaluating mucosal activity in UC patients as compared to CRP. The reasons and/or 
involved mechanisms related to this issue should be clearly discussed.  
 
3. Did the authors examine the clinical backgrounds of UC patients in whom a high 
effectiveness of SAA as compared to CRP was shown? Such analysis may be useful for 
making a proper choice between CRP and S AA in clinical settings.  
 
4. A recently published study (Dig Liver Dis. 2018 Jun;50(6):553 -558. 2018) revealed 
that SAA level was correlated with endoscopic findings in patients with Crohn's disease 
(CD). Those authors concluded that SAA is a possible bioma rker for evaluating 
mucosal healing. It would be good for the present authors to discuss the clinical utility 
of SAA in UC as compared to CD patients.  
 
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 th e necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
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 asses s any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this man uscript  
 
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 f ive years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2.  Do you  hold any stocks or shares in an organisation t hat 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 for 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 understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the webs ite 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 nam ed report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant