Reviewer ’s report  
 
Title: Increased circulating total bile acid levels were associated with  organ failure in patients 
with acute pancreatitis  
 
Version: 0 Date: 20 Jan 2020  
 
Reviewer: Atsushi Irisawa  
 
Reviewer's report:  
This research article showed t hat the increase of circulating total bile acid (TBA) in early stage 
of acute pancreatitis (AP) is independently related to organ failure (OF), which indicates the 
adverse prognosis of AP patients. As you mentioned, early identification of risk factors of OF 
may allow for earlier treatment intervention of AP. So your point of view is very important. 
However, it seems that there are some problems to mention your conclusions.  
 
1. At first, I think that biliary pancreatitis should be excluded in this study. T BA increase in 
biliary pancreatitis due to bile outflow obstruction. For these reasons, it would be difficult to use 
TBA as markers for predicting OF in biliary pancreatitis What do you think?  
2. In addition, you mentioned that some studies illuminated tha t the levels of circulating 
TBA were elevated in patients with metabolic diseases such as obesity and type 2 diabetes (page 
4, line11 -13.). Why was there no significant difference in the prevalence of DM between high 
TBA (HTBA) group and the normal TBA (NT BA) group?  
3. Were there Ursodeoxycholic acid (UDCA) patients in this study? I think patients with 
taking UDCA should be excluded from this study because of UDCA pharmacology.  
4. In this study, the selection of patients were (1) within 7 days after onset of AP; (2) TBA 
values available within 7 days after admission. This selection period is too long. BA increase 
when multiple OF and drug -induced liver injury occur during disease progression and treatment. 
What do you think?  
5. You mentioned patients with H TBA were more likely to be drinking (59.3% vs. 28.9%; 
p&lt;0.001). Were these patients denied alcoholic liver disease?  
6. Please describe the cause of the death (e.g. related AP, septic shock due to cholangitis, 
and more).  
7. How did you choose your treatm ent for the pancreatic fluid collection?  
8. Please describe the definition of AP in more detail.  
 
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.  
 
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 assess 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.  
 
I am abl e to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
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, 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 al l 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 tha t I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my na me 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 website along with the authors' 
responses. I agree for my report to be made availab le 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 in cluded as confidential comments 
to the editors, which will n ot be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Increased circulating total bile acid levels were associated with  organ failure in patients 
with acute pancreatitis  
 
Version: 0 Date: 20 Jan 2020  
 
Reviewer: Atsushi Irisawa  
 
Reviewer's report:  
This research article showed t hat the increase of circulating total bile acid (TBA) in early stage 
of acute pancreatitis (AP) is independently related to organ failure (OF), which indicates the 
adverse prognosis of AP patients. As you mentioned, early identification of risk factors of OF 
may allow for earlier treatment intervention of AP. So your point of view is very important. 
However, it seems that there are some problems to mention your conclusions.  
 
1. At first, I think that biliary pancreatitis should be excluded in this study. T BA increase in 
biliary pancreatitis due to bile outflow obstruction. For these reasons, it would be difficult to use 
TBA as markers for predicting OF in biliary pancreatitis What do you think?  
2. In addition, you mentioned that some studies illuminated tha t the levels of circulating 
TBA were elevated in patients with metabolic diseases such as obesity and type 2 diabetes (page 
4, line11 -13.). Why was there no significant difference in the prevalence of DM between high 
TBA (HTBA) group and the normal TBA (NT BA) group?  
3. Were there Ursodeoxycholic acid (UDCA) patients in this study? I think patients with 
taking UDCA should be excluded from this study because of UDCA pharmacology.  
4. In this study, the selection of patients were (1) within 7 days after onset of AP; (2) TBA 
values available within 7 days after admission. This selection period is too long. BA increase 
when multiple OF and drug -induced liver injury occur during disease progression and treatment. 
What do you think?  
5. You mentioned patients with H TBA were more likely to be drinking (59.3% vs. 28.9%; 
p&lt;0.001). Were these patients denied alcoholic liver disease?  
6. Please describe the cause of the death (e.g. related AP, septic shock due to cholangitis, 
and more).  
7. How did you choose your treatm ent for the pancreatic fluid collection?  
8. Please describe the definition of AP in more detail.  
 
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.  
 
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 assess 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.  
 
I am abl e to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
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, 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 al l 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 tha t I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my na me 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 website along with the authors' 
responses. I agree for my report to be made availab le 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 in cluded as confidential comments 
to the editors, which will n ot be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Increased circulating total bile acid levels were associated with  organ failure in patients 
with acute pancreatitis  
 
Version: 0 Date: 20 Jan 2020  
 
Reviewer: Atsushi Irisawa  
 
Reviewer's report:  
This research article showed t hat the increase of circulating total bile acid (TBA) in early stage 
of acute pancreatitis (AP) is independently related to organ failure (OF), which indicates the 
adverse prognosis of AP patients. As you mentioned, early identification of risk factors of OF 
may allow for earlier treatment intervention of AP. So your point of view is very important. 
However, it seems that there are some problems to mention your conclusions.  
 
1. At first, I think that biliary pancreatitis should be excluded in this study. T BA increase in 
biliary pancreatitis due to bile outflow obstruction. For these reasons, it would be difficult to use 
TBA as markers for predicting OF in biliary pancreatitis What do you think?  
2. In addition, you mentioned that some studies illuminated tha t the levels of circulating 
TBA were elevated in patients with metabolic diseases such as obesity and type 2 diabetes (page 
4, line11 -13.). Why was there no significant difference in the prevalence of DM between high 
TBA (HTBA) group and the normal TBA (NT BA) group?  
3. Were there Ursodeoxycholic acid (UDCA) patients in this study? I think patients with 
taking UDCA should be excluded from this study because of UDCA pharmacology.  
4. In this study, the selection of patients were (1) within 7 days after onset of AP; (2) TBA 
values available within 7 days after admission. This selection period is too long. BA increase 
when multiple OF and drug -induced liver injury occur during disease progression and treatment. 
What do you think?  
5. You mentioned patients with H TBA were more likely to be drinking (59.3% vs. 28.9%; 
p&lt;0.001). Were these patients denied alcoholic liver disease?  
6. Please describe the cause of the death (e.g. related AP, septic shock due to cholangitis, 
and more).  
7. How did you choose your treatm ent for the pancreatic fluid collection?  
8. Please describe the definition of AP in more detail.  
 
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.  
 
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 assess 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.  
 
I am abl e to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
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, 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 al l 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 tha t I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my na me 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 website along with the authors' 
responses. I agree for my report to be made availab le 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 in cluded as confidential comments 
to the editors, which will n ot be published.  
 
I agree to the open peer review policy of the journal  
assistant