Reviewer ’s report  
 
Title:  Diagnostic accuracy of controlled attenuation parameter (CAP) as a non -invasive test for 
steatosis in suspected non alcoholic fatty liver disease: a systematic review and meta -analysis  
 
Version: 0 Date: 26 Aug 2018 
 
Reviewer:  Fabio  Piscaglia  
 
Reviewer’s report:  
 
Please include all comments for the authors in this box rather than uploading your report as an 
attachment. Please only upload as attachments annotated versions of manuscripts, graphs, 
supporting materials or other aspe cts of your report which cannot be included in a text format.  
 
Please overwrite this text when adding your comments to the authors.  
 
There are a few mispelling and typos.  
 
Page 13. Line 3 from bottom.  Probably they would not like to state "is without bias", but rather 
"may be imperfect" or something similar.  
 
For what concerns me, as a clinician, the analysis appears sound. However, the statistical 
analysis represent the core of this study, once the s tudies have been selected. I suggest the 
manuscript to be reviewed by a statistician as well.  
 
One major concer is how the CAP applies to the everyday patient, who would not have fitted into 
a study (no indication for biopsy). In fact, the findings of thi s study could only apply to patients 
who (even in a study) were considered to usefully undergo a biopsy, which clearly does not 
represent the concutive patients entering ultrasound labs or hepatology offices. Moreover, this 
study declare to be focused in p atients with histology proven NAFLD. The Authors state "In this 
study, we analyzed the diagnostic accuracy of CAP in distinguishing different stages of hepatic 
steatosis in liver -biopsy proven NAFLD patients, and assessed the possible contributing factors 
affecting CAP values"  
 
However, a number of patients had no significant liver steatosis (S0). How could a diagnosis of 
histological NAFLD be achieved in patients in whom histology showed no steatosis?. What sort 
of disease did these patients suffer from?  
 
In other terms, the findings of present study applies only to patients for whom a clinical 
suspicion of NAFLD has been raised (at least I guess so) and for whom a biopsy could be 
indicated. I expect that most patients with fully normal liver transaminses (a large majority of 
patients in medical offices) are not represented in this study. These are general considerations, 
however, I believe it is very important to put each study in the specific context in which the 
diagnostic tool will be applied and this s tudy carried out an extensive statistical analysis but did 
not deal enough about the correlation between the starting studies and the impact of the 
conclusions of the current study.  
 
Are the methods appropriate and well described?  
If not, please specify wh at 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 r equire 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:  
 
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 financia lly 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 y ou 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 a research contract with Esaote and received a Speaker Bureaus honorarium from Meda 
Pharma 3 years ago.  
 
Other relationship with industry (not related to the present study): Bayer, Bracco, EISAI, 
Guerbet.  
 
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 publicati on, 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:  Diagnostic accuracy of controlled attenuation parameter (CAP) as a non -invasive test for 
steatosis in suspected non alcoholic fatty liver disease: a systematic review and meta -analysis  
 
Version: 0 Date: 26 Aug 2018 
 
Reviewer:  Fabio  Piscaglia  
 
Reviewer’s report:  
 
Please include all comments for the authors in this box rather than uploading your report as an 
attachment. Please only upload as attachments annotated versions of manuscripts, graphs, 
supporting materials or other aspe cts of your report which cannot be included in a text format.  
 
Please overwrite this text when adding your comments to the authors.  
 
There are a few mispelling and typos.  
 
Page 13. Line 3 from bottom.  Probably they would not like to state "is without bias", but rather 
"may be imperfect" or something similar.  
 
For what concerns me, as a clinician, the analysis appears sound. However, the statistical 
analysis represent the core of this study, once the s tudies have been selected. I suggest the 
manuscript to be reviewed by a statistician as well.  
 
One major concer is how the CAP applies to the everyday patient, who would not have fitted into 
a study (no indication for biopsy). In fact, the findings of thi s study could only apply to patients 
who (even in a study) were considered to usefully undergo a biopsy, which clearly does not 
represent the concutive patients entering ultrasound labs or hepatology offices. Moreover, this 
study declare to be focused in p atients with histology proven NAFLD. The Authors state "In this 
study, we analyzed the diagnostic accuracy of CAP in distinguishing different stages of hepatic 
steatosis in liver -biopsy proven NAFLD patients, and assessed the possible contributing factors 
affecting CAP values"  
 
However, a number of patients had no significant liver steatosis (S0). How could a diagnosis of 
histological NAFLD be achieved in patients in whom histology showed no steatosis?. What sort 
of disease did these patients suffer from?  
 
In other terms, the findings of present study applies only to patients for whom a clinical 
suspicion of NAFLD has been raised (at least I guess so) and for whom a biopsy could be 
indicated. I expect that most patients with fully normal liver transaminses (a large majority of 
patients in medical offices) are not represented in this study. These are general considerations, 
however, I believe it is very important to put each study in the specific context in which the 
diagnostic tool will be applied and this s tudy carried out an extensive statistical analysis but did 
not deal enough about the correlation between the starting studies and the impact of the 
conclusions of the current study.  
 
Are the methods appropriate and well described?  
If not, please specify wh at 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 r equire 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:  
 
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 financia lly 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 y ou 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 a research contract with Esaote and received a Speaker Bureaus honorarium from Meda 
Pharma 3 years ago.  
 
Other relationship with industry (not related to the present study): Bayer, Bracco, EISAI, 
Guerbet.  
 
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 publicati on, 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:  Diagnostic accuracy of controlled attenuation parameter (CAP) as a non -invasive test for 
steatosis in suspected non alcoholic fatty liver disease: a systematic review and meta -analysis  
 
Version: 0 Date: 26 Aug 2018 
 
Reviewer:  Fabio  Piscaglia  
 
Reviewer’s report:  
 
Please include all comments for the authors in this box rather than uploading your report as an 
attachment. Please only upload as attachments annotated versions of manuscripts, graphs, 
supporting materials or other aspe cts of your report which cannot be included in a text format.  
 
Please overwrite this text when adding your comments to the authors.  
 
There are a few mispelling and typos.  
 
Page 13. Line 3 from bottom.  Probably they would not like to state "is without bias", but rather 
"may be imperfect" or something similar.  
 
For what concerns me, as a clinician, the analysis appears sound. However, the statistical 
analysis represent the core of this study, once the s tudies have been selected. I suggest the 
manuscript to be reviewed by a statistician as well.  
 
One major concer is how the CAP applies to the everyday patient, who would not have fitted into 
a study (no indication for biopsy). In fact, the findings of thi s study could only apply to patients 
who (even in a study) were considered to usefully undergo a biopsy, which clearly does not 
represent the concutive patients entering ultrasound labs or hepatology offices. Moreover, this 
study declare to be focused in p atients with histology proven NAFLD. The Authors state "In this 
study, we analyzed the diagnostic accuracy of CAP in distinguishing different stages of hepatic 
steatosis in liver -biopsy proven NAFLD patients, and assessed the possible contributing factors 
affecting CAP values"  
 
However, a number of patients had no significant liver steatosis (S0). How could a diagnosis of 
histological NAFLD be achieved in patients in whom histology showed no steatosis?. What sort 
of disease did these patients suffer from?  
 
In other terms, the findings of present study applies only to patients for whom a clinical 
suspicion of NAFLD has been raised (at least I guess so) and for whom a biopsy could be 
indicated. I expect that most patients with fully normal liver transaminses (a large majority of 
patients in medical offices) are not represented in this study. These are general considerations, 
however, I believe it is very important to put each study in the specific context in which the 
diagnostic tool will be applied and this s tudy carried out an extensive statistical analysis but did 
not deal enough about the correlation between the starting studies and the impact of the 
conclusions of the current study.  
 
Are the methods appropriate and well described?  
If not, please specify wh at 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 r equire 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:  
 
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 financia lly 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 y ou 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 a research contract with Esaote and received a Speaker Bureaus honorarium from Meda 
Pharma 3 years ago.  
 
Other relationship with industry (not related to the present study): Bayer, Bracco, EISAI, 
Guerbet.  
 
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 publicati on, 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