Reviewer’s report
Title: Validity of biopsy-based drug effects in a diet-induced obese mouse model of biopsyconfirmed
NASH
Version: 0 Date: 10 Oct 2019
Reviewer: Paul Kelly
Reviewer's report:
This is an interesting manuscript describing methodological work related to assessment of NASH. The
question is: does a single biopsy fully represent the changes which drug treatment can bring about in
this animal model. The answer appears to be, with certain caveats, yes. The authors also go on to
describe the effects of three pharmacological interventions applied to this model of NASH. The three
drugs appear to do different things. The manuscript is well-written and the scientific method sound.
However, I would recommend three changes:
1 Re-consider the title. Is this really about methodology, or was the real objective to describe the effects
of the drugs? The authors should consider if it might be better to focus the title on the pharmacological
effects, with the stereo logy as a valuable preparatory step.
2 What is INT-767? While I appreciate that this is a drug in development, some summary of its
mechanism of action would make the paper much more attractive.
3 The legend to Figure 2 is difficult to read and should be re-worked. Why is the term "slaps" used?
This means nothing to me. If it is a term used in some stereology work it needs to be explained,
otherwise this legend, and related text, should be re-written. 
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.
Yes
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  additional  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 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 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, which will not
be published.
I agree to the open peer review policy of the journal
Reviewer’s report
Title: Validity of biopsy-based drug effects in a diet-induced obese mouse model of biopsyconfirmed
NASH
Version: 0 Date: 10 Oct 2019
Reviewer: Paul Kelly
Reviewer's report:
This is an interesting manuscript describing methodological work related to assessment of NASH. The
question is: does a single biopsy fully represent the changes which drug treatment can bring about in
this animal model. The answer appears to be, with certain caveats, yes. The authors also go on to
describe the effects of three pharmacological interventions applied to this model of NASH. The three
drugs appear to do different things. The manuscript is well-written and the scientific method sound.
However, I would recommend three changes:
1 Re-consider the title. Is this really about methodology, or was the real objective to describe the effects
of the drugs? The authors should consider if it might be better to focus the title on the pharmacological
effects, with the stereo logy as a valuable preparatory step.
2 What is INT-767? While I appreciate that this is a drug in development, some summary of its
mechanism of action would make the paper much more attractive.
3 The legend to Figure 2 is difficult to read and should be re-worked. Why is the term "slaps" used?
This means nothing to me. If it is a term used in some stereology work it needs to be explained,
otherwise this legend, and related text, should be re-written. 
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.
Yes
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  additional  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 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 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, 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: Validity of biopsy-based drug effects in a diet-induced obese mouse model of biopsyconfirmed
NASH
Version: 0 Date: 10 Oct 2019
Reviewer: Paul Kelly
Reviewer's report:
This is an interesting manuscript describing methodological work related to assessment of NASH. The
question is: does a single biopsy fully represent the changes which drug treatment can bring about in
this animal model. The answer appears to be, with certain caveats, yes. The authors also go on to
describe the effects of three pharmacological interventions applied to this model of NASH. The three
drugs appear to do different things. The manuscript is well-written and the scientific method sound.
However, I would recommend three changes:
1 Re-consider the title. Is this really about methodology, or was the real objective to describe the effects
of the drugs? The authors should consider if it might be better to focus the title on the pharmacological
effects, with the stereo logy as a valuable preparatory step.
2 What is INT-767? While I appreciate that this is a drug in development, some summary of its
mechanism of action would make the paper much more attractive.
3 The legend to Figure 2 is difficult to read and should be re-worked. Why is the term "slaps" used?
This means nothing to me. If it is a term used in some stereology work it needs to be explained,
otherwise this legend, and related text, should be re-written. 
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.
Yes
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  additional  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 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 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, which will not
be published.
I agree to the open peer review policy of the journal
assistant