Reviewer ’s report  
 
Title: Frequently abnormal serum gamma -glutamyl transferase act ivity is associated with future 
development of fatty l iver: a retrospective cohort study  
 
Version: 0 Date: 17 May 2020  
 
Reviewer's report:  
 
Because GGT is significantly associated with metabolic syndrome and oxidative stress, its 
association with future development of NAFLD is quite plausible. This is a proof of concept 
study, though lacks novelty. Overall it is written well and easy to follow. The retrospective 
design and use of ultrasound for diagnosing NAFLD,  which has poor sen sitivity for mild hepatic 
steatosis, are the major drawback. Propensity matched analysis and relatively longer follow -up 
are the strength of this study. Some my points and suggestions are:  
 
-Before categorising patients arbitrarily on the basis of GTT cut -offs, authors should have first 
assessed whether GGT had an independent role in predicting the occurrence of NAFLD in entire 
cohort.  
 
-In limitation, Authors need to highlight that GGT is a  dynamic variable, its values might have 
changed differently in both the groups during study time which may have affected the results. 
Similarly,  differential consumption of alcohol and food, differences in physical activities and 
medications (such as ant i-oxidants)  between the groups might have affected the incidence of 
NAFLD during follow -up.  
 
-Authors concluded that TG was independent predictor of NAFLD occurrence in high GGT 
group. However, in propensity matched subjects, the value of TG was not high er in abnormal 
GGT groups compared to the normal ones (table 1). Authors need to explain this discrepancy 
which is likely to be because of some confounders, and may think of doing re -analysis in 
matched subjects or may  change the conclusions.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessa ry 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.  
 
Unable to assess  
Are you able to assess any statistics in the manus cript or would yo u 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 able 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 financially from the 
publi cation 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 curr ently 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  
 
Reviewer Publication Consent. 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 ) if this 
manuscript is accepted for publication. Any comments that I do not wish to be included in the 
published report have been included as confidential comments to the editor,  which will not be 
published.  If you are not happy for us to publish this report, please contact th e edi torial office 
before completin g the review.  If you wish, you can include your name in your published report. 
Please note you must  decide whether to include your name at the start of the process and confirm 
this decision whenever  prompted. If you change  your decision later, we will not be able to 
publish your name.  
 
I agree to the terms of the CC -BY 4.0 license; please do not publish my name with my report.  
(default)  
Reviewer ’s report  
 
Title: Frequently abnormal serum gamma -glutamyl transferase act ivity is associated with future 
development of fatty l iver: a retrospective cohort study  
 
Version: 0 Date: 17 May 2020  
 
Reviewer's report:  
 
Because GGT is significantly associated with metabolic syndrome and oxidative stress, its 
association with future development of NAFLD is quite plausible. This is a proof of concept 
study, though lacks novelty. Overall it is written well and easy to follow. The retrospective 
design and use of ultrasound for diagnosing NAFLD,  which has poor sen sitivity for mild hepatic 
steatosis, are the major drawback. Propensity matched analysis and relatively longer follow -up 
are the strength of this study. Some my points and suggestions are:  
 
-Before categorising patients arbitrarily on the basis of GTT cut -offs, authors should have first 
assessed whether GGT had an independent role in predicting the occurrence of NAFLD in entire 
cohort.  
 
-In limitation, Authors need to highlight that GGT is a  dynamic variable, its values might have 
changed differently in both the groups during study time which may have affected the results. 
Similarly,  differential consumption of alcohol and food, differences in physical activities and 
medications (such as ant i-oxidants)  between the groups might have affected the incidence of 
NAFLD during follow -up.  
 
-Authors concluded that TG was independent predictor of NAFLD occurrence in high GGT 
group. However, in propensity matched subjects, the value of TG was not high er in abnormal 
GGT groups compared to the normal ones (table 1). Authors need to explain this discrepancy 
which is likely to be because of some confounders, and may think of doing re -analysis in 
matched subjects or may  change the conclusions.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessa ry 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.  
 
Unable to assess  
Are you able to assess any statistics in the manus cript or would yo u 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 able 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 financially from the 
publi cation 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 curr ently 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  
 
Reviewer Publication Consent. 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 ) if this 
manuscript is accepted for publication. Any comments that I do not wish to be included in the 
published report have been included as confidential comments to the editor,  which will not be 
published.  If you are not happy for us to publish this report, please contact th e edi torial office 
before completin g the review.  If you wish, you can include your name in your published report. 
Please note you must  decide whether to include your name at the start of the process and confirm 
this decision whenever  prompted. If you change  your decision later, we will not be able to 
publish your name.  
 
I agree to the terms of the CC -BY 4.0 license; please do not publish my name with my report.  
(default)  
Please review this paper.
user
Reviewer ’s report  
 
Title: Frequently abnormal serum gamma -glutamyl transferase act ivity is associated with future 
development of fatty l iver: a retrospective cohort study  
 
Version: 0 Date: 17 May 2020  
 
Reviewer's report:  
 
Because GGT is significantly associated with metabolic syndrome and oxidative stress, its 
association with future development of NAFLD is quite plausible. This is a proof of concept 
study, though lacks novelty. Overall it is written well and easy to follow. The retrospective 
design and use of ultrasound for diagnosing NAFLD,  which has poor sen sitivity for mild hepatic 
steatosis, are the major drawback. Propensity matched analysis and relatively longer follow -up 
are the strength of this study. Some my points and suggestions are:  
 
-Before categorising patients arbitrarily on the basis of GTT cut -offs, authors should have first 
assessed whether GGT had an independent role in predicting the occurrence of NAFLD in entire 
cohort.  
 
-In limitation, Authors need to highlight that GGT is a  dynamic variable, its values might have 
changed differently in both the groups during study time which may have affected the results. 
Similarly,  differential consumption of alcohol and food, differences in physical activities and 
medications (such as ant i-oxidants)  between the groups might have affected the incidence of 
NAFLD during follow -up.  
 
-Authors concluded that TG was independent predictor of NAFLD occurrence in high GGT 
group. However, in propensity matched subjects, the value of TG was not high er in abnormal 
GGT groups compared to the normal ones (table 1). Authors need to explain this discrepancy 
which is likely to be because of some confounders, and may think of doing re -analysis in 
matched subjects or may  change the conclusions.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessa ry 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.  
 
Unable to assess  
Are you able to assess any statistics in the manus cript or would yo u 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 able 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 financially from the 
publi cation 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 curr ently 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  
 
Reviewer Publication Consent. 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 ) if this 
manuscript is accepted for publication. Any comments that I do not wish to be included in the 
published report have been included as confidential comments to the editor,  which will not be 
published.  If you are not happy for us to publish this report, please contact th e edi torial office 
before completin g the review.  If you wish, you can include your name in your published report. 
Please note you must  decide whether to include your name at the start of the process and confirm 
this decision whenever  prompted. If you change  your decision later, we will not be able to 
publish your name.  
 
I agree to the terms of the CC -BY 4.0 license; please do not publish my name with my report.  
(default)  
assistant