Reviewer ’s report  
 
Title: Physical activity intervention for non -diabetic patients  with non -alcoholic fatty liver 
disease: a meta -analysis of randomized controlled trials  
 
Version: 0 Date: 31 Dec 2019  
 
Reviewer: Umberto Vespasiani -Gentilucci  
 
Reviewer's report:  
Here Wang et al.  present a meta -analysis of randomized controlled trials focusing on the effect 
of physical activity on hepatic enzymes, serum lipids and glucose metabolism in NAFLD 
patients.  
 
I have the following points:  
1) Authors state that studies including NAFLD patients with diabetes w ere excluded from the 
analysis due to the potential confounding effect of anti -diabetic medications. First of all, a better 
check of precise inclusion/exclusion criteria of each study should be performed (see for example 
Hallsworth el al., where diabetic p atients on metformin were included). Secondly, I don't 
understand why diabetic patients sould be excluded: 1) It is an important limit, since a significant 
proportion of NAFLD patients are diabetic; 2) the problem of anti -diabetic drugs is always 
assessed and solved in each reference study by matching with an adequate control population. 
Otherwise, the title of the paper should be at least modified in "Physical activity intervention for 
non-diabetic patients with non -alcoholic fatty liver disease: …".  
2) On e of the main point when evaluating the efficacy of any kind of treatment in NAFLD 
patients is the effect on the intra -hepatic lipid load (as previously assessed in their meta -analysis 
by Orci LA et al, Clin Gastroenterol Hepatol 2016).  Why this point was  not assessed in this 
work, at least in the minority of the study sample where this evaluation was available?  
 
 
Are the methods appropriate and well desc ribed?  
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.  
 
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 addit ional statistical review  
 
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, 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 futu re? 
 
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 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 f or publication, my named report 
including any attachments I upload will be posted on the website along with th e authors' 
responses. I agree for my report to be made available under an Open Acc ess 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 not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Physical activity intervention for non -diabetic patients  with non -alcoholic fatty liver 
disease: a meta -analysis of randomized controlled trials  
 
Version: 0 Date: 31 Dec 2019  
 
Reviewer: Umberto Vespasiani -Gentilucci  
 
Reviewer's report:  
Here Wang et al.  present a meta -analysis of randomized controlled trials focusing on the effect 
of physical activity on hepatic enzymes, serum lipids and glucose metabolism in NAFLD 
patients.  
 
I have the following points:  
1) Authors state that studies including NAFLD patients with diabetes w ere excluded from the 
analysis due to the potential confounding effect of anti -diabetic medications. First of all, a better 
check of precise inclusion/exclusion criteria of each study should be performed (see for example 
Hallsworth el al., where diabetic p atients on metformin were included). Secondly, I don't 
understand why diabetic patients sould be excluded: 1) It is an important limit, since a significant 
proportion of NAFLD patients are diabetic; 2) the problem of anti -diabetic drugs is always 
assessed and solved in each reference study by matching with an adequate control population. 
Otherwise, the title of the paper should be at least modified in "Physical activity intervention for 
non-diabetic patients with non -alcoholic fatty liver disease: …".  
2) On e of the main point when evaluating the efficacy of any kind of treatment in NAFLD 
patients is the effect on the intra -hepatic lipid load (as previously assessed in their meta -analysis 
by Orci LA et al, Clin Gastroenterol Hepatol 2016).  Why this point was  not assessed in this 
work, at least in the minority of the study sample where this evaluation was available?  
 
 
Are the methods appropriate and well desc ribed?  
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.  
 
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 addit ional statistical review  
 
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, 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 futu re? 
 
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 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 f or publication, my named report 
including any attachments I upload will be posted on the website along with th e authors' 
responses. I agree for my report to be made available under an Open Acc ess 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 not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Physical activity intervention for non -diabetic patients  with non -alcoholic fatty liver 
disease: a meta -analysis of randomized controlled trials  
 
Version: 0 Date: 31 Dec 2019  
 
Reviewer: Umberto Vespasiani -Gentilucci  
 
Reviewer's report:  
Here Wang et al.  present a meta -analysis of randomized controlled trials focusing on the effect 
of physical activity on hepatic enzymes, serum lipids and glucose metabolism in NAFLD 
patients.  
 
I have the following points:  
1) Authors state that studies including NAFLD patients with diabetes w ere excluded from the 
analysis due to the potential confounding effect of anti -diabetic medications. First of all, a better 
check of precise inclusion/exclusion criteria of each study should be performed (see for example 
Hallsworth el al., where diabetic p atients on metformin were included). Secondly, I don't 
understand why diabetic patients sould be excluded: 1) It is an important limit, since a significant 
proportion of NAFLD patients are diabetic; 2) the problem of anti -diabetic drugs is always 
assessed and solved in each reference study by matching with an adequate control population. 
Otherwise, the title of the paper should be at least modified in "Physical activity intervention for 
non-diabetic patients with non -alcoholic fatty liver disease: …".  
2) On e of the main point when evaluating the efficacy of any kind of treatment in NAFLD 
patients is the effect on the intra -hepatic lipid load (as previously assessed in their meta -analysis 
by Orci LA et al, Clin Gastroenterol Hepatol 2016).  Why this point was  not assessed in this 
work, at least in the minority of the study sample where this evaluation was available?  
 
 
Are the methods appropriate and well desc ribed?  
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.  
 
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 addit ional statistical review  
 
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, 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 futu re? 
 
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 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 f or publication, my named report 
including any attachments I upload will be posted on the website along with th e authors' 
responses. I agree for my report to be made available under an Open Acc ess 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 not be published.  
 
I agree to the open peer review policy of the journal  
assistant