Reviewer ’s report  
 
Title: Increased circulating total bile acid levels were associated with  organ failure in patients 
with acute pancreatitis  
 
Version: 0 Date: 23 Jan 2020  
 
Reviewer: Ali Alexander Aghdassi  
 
Reviewer's report:  
In this retrospective study Xie et al. correlated the levels of circulating tot al bile acids (TBS) 
with severity of acute pancreatitis. Severity of AP was classified according to the Determinant -
based Classification. The TBA levels were divided into two groups (high TBA and normal TBA 
group) by choosing a threshold of 10 μmol/L. The authors found a higher incidence of organ 
failure in the HTBA group compared to the NTBA group. In particular there was a higher rate of 
pulmonary and renal failure. Moreover, the authors found an association of high TBA levels and 
(peri -)pancreatic necros is and mortality.  
 
The authors address an important clinical question because an early detection of complications of 
acute pancreatitis is highly desirable. However, I have concerns regarding the design of this 
study.  
 
Major concern:  
1.) The authors have selected the highest TBA level within 7 days, which is a quite long time 
period. During that time acute pancreatitis often has progressed and organ failure has developed. 
On the other hand the majority of patients with mild AP have already recovered. That is why this 
study can't answer whether total bile acids are of predictive value. It just describes an association 
of elevated TBA values and organ failure. However, for organ failure other more commonly used 
laboratory parameters, that are already in clini cal routine, are helpful, too.  
As mentioned by the authors in their discussion an early and accurate prediction of organ failure 
(p. 10, l. 12 -14) is very important for treatment of acute pancreatitis but for this earlier time 
points for TBA measurements would be more valuable. Although the authors have addressed this 
point in their discussion section as well by comparing their results with a study by Maleszka et al 
(Maleszka A, Int Mol Sci 2017) they don't provide information whether TBA levels at hospita l 
admission or maybe after 24 hours might correlate with complications of acute pancreatitis. Data 
regarding TBA levels at hospital admission or shortly after would be more helpful and also more 
convenient, rather than daily TBA measurements during the fir st week.  
Minor concerns:  
 
1.) The authors need to state, which assay was used for measurement of TBA levels.  
2.) Results (p. 7, l. 40 -43): Why were these 659 patients with AP for more than 7 days 
excluded?  
3.) The manuscript needs further English language editing because of grammatical errors, i.e. 
on page 7, l. 46 -54 or page 11, l. 31 -42. 
 
 
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.  
 
No 
 
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: 23 Jan 2020  
 
Reviewer: Ali Alexander Aghdassi  
 
Reviewer's report:  
In this retrospective study Xie et al. correlated the levels of circulating tot al bile acids (TBS) 
with severity of acute pancreatitis. Severity of AP was classified according to the Determinant -
based Classification. The TBA levels were divided into two groups (high TBA and normal TBA 
group) by choosing a threshold of 10 μmol/L. The authors found a higher incidence of organ 
failure in the HTBA group compared to the NTBA group. In particular there was a higher rate of 
pulmonary and renal failure. Moreover, the authors found an association of high TBA levels and 
(peri -)pancreatic necros is and mortality.  
 
The authors address an important clinical question because an early detection of complications of 
acute pancreatitis is highly desirable. However, I have concerns regarding the design of this 
study.  
 
Major concern:  
1.) The authors have selected the highest TBA level within 7 days, which is a quite long time 
period. During that time acute pancreatitis often has progressed and organ failure has developed. 
On the other hand the majority of patients with mild AP have already recovered. That is why this 
study can't answer whether total bile acids are of predictive value. It just describes an association 
of elevated TBA values and organ failure. However, for organ failure other more commonly used 
laboratory parameters, that are already in clini cal routine, are helpful, too.  
As mentioned by the authors in their discussion an early and accurate prediction of organ failure 
(p. 10, l. 12 -14) is very important for treatment of acute pancreatitis but for this earlier time 
points for TBA measurements would be more valuable. Although the authors have addressed this 
point in their discussion section as well by comparing their results with a study by Maleszka et al 
(Maleszka A, Int Mol Sci 2017) they don't provide information whether TBA levels at hospita l 
admission or maybe after 24 hours might correlate with complications of acute pancreatitis. Data 
regarding TBA levels at hospital admission or shortly after would be more helpful and also more 
convenient, rather than daily TBA measurements during the fir st week.  
Minor concerns:  
 
1.) The authors need to state, which assay was used for measurement of TBA levels.  
2.) Results (p. 7, l. 40 -43): Why were these 659 patients with AP for more than 7 days 
excluded?  
3.) The manuscript needs further English language editing because of grammatical errors, i.e. 
on page 7, l. 46 -54 or page 11, l. 31 -42. 
 
 
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.  
 
No 
 
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: 23 Jan 2020  
 
Reviewer: Ali Alexander Aghdassi  
 
Reviewer's report:  
In this retrospective study Xie et al. correlated the levels of circulating tot al bile acids (TBS) 
with severity of acute pancreatitis. Severity of AP was classified according to the Determinant -
based Classification. The TBA levels were divided into two groups (high TBA and normal TBA 
group) by choosing a threshold of 10 μmol/L. The authors found a higher incidence of organ 
failure in the HTBA group compared to the NTBA group. In particular there was a higher rate of 
pulmonary and renal failure. Moreover, the authors found an association of high TBA levels and 
(peri -)pancreatic necros is and mortality.  
 
The authors address an important clinical question because an early detection of complications of 
acute pancreatitis is highly desirable. However, I have concerns regarding the design of this 
study.  
 
Major concern:  
1.) The authors have selected the highest TBA level within 7 days, which is a quite long time 
period. During that time acute pancreatitis often has progressed and organ failure has developed. 
On the other hand the majority of patients with mild AP have already recovered. That is why this 
study can't answer whether total bile acids are of predictive value. It just describes an association 
of elevated TBA values and organ failure. However, for organ failure other more commonly used 
laboratory parameters, that are already in clini cal routine, are helpful, too.  
As mentioned by the authors in their discussion an early and accurate prediction of organ failure 
(p. 10, l. 12 -14) is very important for treatment of acute pancreatitis but for this earlier time 
points for TBA measurements would be more valuable. Although the authors have addressed this 
point in their discussion section as well by comparing their results with a study by Maleszka et al 
(Maleszka A, Int Mol Sci 2017) they don't provide information whether TBA levels at hospita l 
admission or maybe after 24 hours might correlate with complications of acute pancreatitis. Data 
regarding TBA levels at hospital admission or shortly after would be more helpful and also more 
convenient, rather than daily TBA measurements during the fir st week.  
Minor concerns:  
 
1.) The authors need to state, which assay was used for measurement of TBA levels.  
2.) Results (p. 7, l. 40 -43): Why were these 659 patients with AP for more than 7 days 
excluded?  
3.) The manuscript needs further English language editing because of grammatical errors, i.e. 
on page 7, l. 46 -54 or page 11, l. 31 -42. 
 
 
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.  
 
No 
 
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