Reviewer ’s report  
Title: Response of fibroblast growth factor 1 9 and bile acid synthes is after a body weight -
adjusted oral fat tolerance test in overweight and obese NAFLD patients: a non -randomized 
controlled pilot  trial 
 
Version: 0 Date: 27 Jan 2017  
 
Reviewer: Günter Fauler  
 
Reviewer's report:  
Although it is difficult to reach a representative number of patients, especially in pilot trials, the 
number of samples here (12 -16 in each group) seems very low to formulate suitable statistical 
conclusions.  
As there was nearly no effect on BA synthesis , statistical differences can be seen more or less 
only in some changes of FGF19 concentrations. Hence, these results should be highlighted and 
both the mechanisms and consequences should be discussed more detailed in the 'discussion' 
section. Especially, why FGF19 levels are lower in overweight patients than in obese ones after 
2h?  
The authors showed that individual basal concentrations of FGF19 were between 17 and 392 
pg/ml with an inconsistent distribution, so one better should calculate medians (and IQ R) instead 
of means. Furthermore, I suggest that presentations of the data (especially when the number of 
samples is low), where all individual trends over time points are illustrated, could be better 
clarify, whether there are differences in response by p atients with low or high basal 
concentrations.  
The discussion section is very confusing and not easy to read, maybe through to repeated mixing 
of themes within one paragraph and the introduction of new findings from the literature (e.g. 
βKlotho), never men tioned before (and therefore also not analyzed in this cohort). Some of the 
dim suggestions and crosslinks should be specified and substantiated. A final conclusion could 
highlight the findings with a preceding hypothesis in the introduction. In summary, a  continuous 
'red thread' is recommended.  
Special remarks:  
In Tab 2 the results regarding cholesterol, C4 and bile acids can be shown in a supplemental 
table (BAs are shown also in Fig 4).  
Supplemental Tab1: Is something known about medication of patients (e.g. 
hypercholesterolemia: 6 patients in overweight, 2 in obesity?) or insulin resistance?  
Fig1/4/7: what is the meaning of the asterisks (case number?) and what scale is used?  
Fig2/3/5/6/8/9: A correlation curve would demonstrate the correlation more cle arly. 
Fig6: Really necessary? Correlation between cholesterol and bile acids is obvious.  
Fig8/9: Does it make sense to correlate one target with another target, measured at different time 
points?  
Fig9: If you exclude the one high -C4/chol -value (maybe an ou tlier?, difficult to say in such a 
small cohort?) the correlation will be quite different or disappear?.   
Correct spelling (native speaker?)  
 
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 conclusio ns 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 recommend additional statistical review  
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, fees, 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, eith er 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 u nderstand 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 repor t 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 e ditors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
Title: Response of fibroblast growth factor 1 9 and bile acid synthes is after a body weight -
adjusted oral fat tolerance test in overweight and obese NAFLD patients: a non -randomized 
controlled pilot  trial 
 
Version: 0 Date: 27 Jan 2017  
 
Reviewer: Günter Fauler  
 
Reviewer's report:  
Although it is difficult to reach a representative number of patients, especially in pilot trials, the 
number of samples here (12 -16 in each group) seems very low to formulate suitable statistical 
conclusions.  
As there was nearly no effect on BA synthesis , statistical differences can be seen more or less 
only in some changes of FGF19 concentrations. Hence, these results should be highlighted and 
both the mechanisms and consequences should be discussed more detailed in the 'discussion' 
section. Especially, why FGF19 levels are lower in overweight patients than in obese ones after 
2h?  
The authors showed that individual basal concentrations of FGF19 were between 17 and 392 
pg/ml with an inconsistent distribution, so one better should calculate medians (and IQ R) instead 
of means. Furthermore, I suggest that presentations of the data (especially when the number of 
samples is low), where all individual trends over time points are illustrated, could be better 
clarify, whether there are differences in response by p atients with low or high basal 
concentrations.  
The discussion section is very confusing and not easy to read, maybe through to repeated mixing 
of themes within one paragraph and the introduction of new findings from the literature (e.g. 
βKlotho), never men tioned before (and therefore also not analyzed in this cohort). Some of the 
dim suggestions and crosslinks should be specified and substantiated. A final conclusion could 
highlight the findings with a preceding hypothesis in the introduction. In summary, a  continuous 
'red thread' is recommended.  
Special remarks:  
In Tab 2 the results regarding cholesterol, C4 and bile acids can be shown in a supplemental 
table (BAs are shown also in Fig 4).  
Supplemental Tab1: Is something known about medication of patients (e.g. 
hypercholesterolemia: 6 patients in overweight, 2 in obesity?) or insulin resistance?  
Fig1/4/7: what is the meaning of the asterisks (case number?) and what scale is used?  
Fig2/3/5/6/8/9: A correlation curve would demonstrate the correlation more cle arly. 
Fig6: Really necessary? Correlation between cholesterol and bile acids is obvious.  
Fig8/9: Does it make sense to correlate one target with another target, measured at different time 
points?  
Fig9: If you exclude the one high -C4/chol -value (maybe an ou tlier?, difficult to say in such a 
small cohort?) the correlation will be quite different or disappear?.   
Correct spelling (native speaker?)  
 
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 conclusio ns 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 recommend additional statistical review  
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, fees, 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, eith er 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 u nderstand 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 repor t 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 e ditors, 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: Response of fibroblast growth factor 1 9 and bile acid synthes is after a body weight -
adjusted oral fat tolerance test in overweight and obese NAFLD patients: a non -randomized 
controlled pilot  trial 
 
Version: 0 Date: 27 Jan 2017  
 
Reviewer: Günter Fauler  
 
Reviewer's report:  
Although it is difficult to reach a representative number of patients, especially in pilot trials, the 
number of samples here (12 -16 in each group) seems very low to formulate suitable statistical 
conclusions.  
As there was nearly no effect on BA synthesis , statistical differences can be seen more or less 
only in some changes of FGF19 concentrations. Hence, these results should be highlighted and 
both the mechanisms and consequences should be discussed more detailed in the 'discussion' 
section. Especially, why FGF19 levels are lower in overweight patients than in obese ones after 
2h?  
The authors showed that individual basal concentrations of FGF19 were between 17 and 392 
pg/ml with an inconsistent distribution, so one better should calculate medians (and IQ R) instead 
of means. Furthermore, I suggest that presentations of the data (especially when the number of 
samples is low), where all individual trends over time points are illustrated, could be better 
clarify, whether there are differences in response by p atients with low or high basal 
concentrations.  
The discussion section is very confusing and not easy to read, maybe through to repeated mixing 
of themes within one paragraph and the introduction of new findings from the literature (e.g. 
βKlotho), never men tioned before (and therefore also not analyzed in this cohort). Some of the 
dim suggestions and crosslinks should be specified and substantiated. A final conclusion could 
highlight the findings with a preceding hypothesis in the introduction. In summary, a  continuous 
'red thread' is recommended.  
Special remarks:  
In Tab 2 the results regarding cholesterol, C4 and bile acids can be shown in a supplemental 
table (BAs are shown also in Fig 4).  
Supplemental Tab1: Is something known about medication of patients (e.g. 
hypercholesterolemia: 6 patients in overweight, 2 in obesity?) or insulin resistance?  
Fig1/4/7: what is the meaning of the asterisks (case number?) and what scale is used?  
Fig2/3/5/6/8/9: A correlation curve would demonstrate the correlation more cle arly. 
Fig6: Really necessary? Correlation between cholesterol and bile acids is obvious.  
Fig8/9: Does it make sense to correlate one target with another target, measured at different time 
points?  
Fig9: If you exclude the one high -C4/chol -value (maybe an ou tlier?, difficult to say in such a 
small cohort?) the correlation will be quite different or disappear?.   
Correct spelling (native speaker?)  
 
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 conclusio ns 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 recommend additional statistical review  
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, fees, 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, eith er 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 u nderstand 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 repor t 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 e ditors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant