Assessment of the association between body composition and risk of non-alcoholic fatty liver

Mohammad Ariya; Farbod Koohpayeh; Alireza Ghaemi; Saeed Osati; Sayed Hossain Davoodi; Jalaledin Mirzay Razzaz; Gholamali Javedan; Elham Ehrampoush; Reza Homayounfar

doi:10.1371/journal.pone.0249223

Peer Review History

Original SubmissionNovember 6, 2020
26 Nov 2020 Decision Letter - Gianfranco D. Alpini, Editor PONE-D-20-34964 Assessment of the association between body composition and risk of Non-alcoholic fatty liver PLOS ONE Dear Dr. Reza Homayounfar, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. The study has merit. Please submit your revised manuscript within 60 days. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Gianfranco D. Alpini Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. 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We will update your Data Availability statement on your behalf to reflect the information you provide. 6. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: No Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: In the current manuscript, Mohammad et al. aimed to study the association between body composition and risk of non-alcoholic fatty liver (NAFLD) development. The authors recruited 2160 patient samples from the nutrition clinics between 2016 and 2017. To determine NAFLD, they used FiroScanTM to determine the controlled attenuation parameter (CAP) score which has been used to define steatosis grade. The body composition was examined by using the dual-energy X-ray absorptiometry (DXA) technique. It was found that fat-free tissue is negatively correlated with NAFLD. Besides, percentages of fat tissue in different body compositions are highly correlated with the risk of NAFLD. Overall, the current study has some clinical importance in guiding the application of fat contents in body composition for the prediction of NAFLD development. However, several issues identified in this manuscript should be further clarified by the authors. 1. The manuscript should be proofread by professional editing service. 2. Table 2 is confused. The authors may consider separating the results into 2 tables including one in males and another one in females. 3. Based on your interpretation, the female would have a high risk of developing NAFLD, if they have total fat and abdominal fat more than 32.23% and 21.42%, respectively. Male would have a high risk of developing NAFLD, if they have total fat and abdominal fat more than 26.73% and 13.76%, respectively. It seems males have a high incidence of developing NAFLD since they require low content of body fat composition to develop NAFLD. In animal studies, it is common that scientists use male mice to study NAFLD because male mice develop NAFLD easily. Could you discuss this aspect in detail in your discussion? 4. Did you check inflammatory cytokines or blood cell contents in your study? It will be interesting to validate if NAFLD patients have a low level of inflammation since adipokines have been linked to inflammation. Reviewer #2: In this study, Ariya et al. seek the association between body composition with risk of NAFLD. The design and procedures of this study sound reasonable and I have no major comments or criticisms for this manuscript. It would be easier for readers to understand if the authors show ROC curves in figures, not Table 3, with p values. Table 2 is confusing and misleading. It looks like the authors show correlation between male and female (e.g., correlation between male left arm fat and female right arm fat), which does not make sense. I think data Table 1 show combined data of male and female, and the authors want to show data for both genders separately. If so, Table 1 is enough to show without Table 2, and if the authors really need to show male and female data separately, format of tables should be same as Table 1, not combined like current Table 2. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0249223.r001
Revision 1
15 Feb 2021 Author Response Response to reviewers Dear Editor and Reviewers We highly appreciate for your detailed and valuable comments on our manuscript. The suggestions were quite helpful for us and we incorporated them in the revised paper. We had referred to literatures and papers and reconstructed the paper to improve the quality of our manuscript. It is important to note that almost all recommendations were corrected and accordingly, we hope these changes could be acceptable to dear editor and respectful reviewers. Our responses to your comments are as follow: Reviewer 1 1. The manuscript should be proofread by professional editing service. • The manuscript was reviewed by two experts and we try to correct all grammatical errors. Also certificate for correcting grammatical mistake have sent with manuscript. 2. Table 2 is confused. The authors may consider separating the results into 2 tables including one in males and another one in females. • Because of the beneficial recommendation of reviewers, table 2 reanalysed with the sex-separated and this analysis was performed in tables 2 and 3. 3. Based on your interpretation, the female would have a high risk of developing NAFLD, if they have total fat and abdominal fat more than 32.23% and 21.42%, respectively. Male would have a high risk of developing NAFLD, if they have total fat and abdominal fat more than 26.73% and 13.76%, respectively. It seems males have a high incidence of developing NAFLD since they require low content of body fat composition to develop NAFLD. In animal studies, it is common that scientists use male mice to study NAFLD because male mice develop NAFLD easily. Could you discuss this aspect in detail in your discussion? • While thanking the reviewers for pointing out this important point, the following sentence was added to the discussion: "Notably, percentage of total fat in women and men of the same age is remarkably different. In fact, total fat is divided into “essential” and “storage" fats. Essential fat has been defined as the fundamental fat for normal physiologic functioning which consists of around 3% and 12% total body of males and females, respectively. On the other hand, storage fat is considered an energy reserve which is expendable and stored in adipose tissue. Thus, the average total fat of an individual (essential fat plus storage fat) in men and women is estimated to be 18-24 percent and 25-31 percent, respectively. Since the percentage of total fat in women is higher than men due to their physiological condition, the amount of total fat affected in diseases such as NAFLD should typically be higher in them than in males. Similarly, in men, the lower amount of total and abdominal fat affects the development of fatty liver, which does not necessarily mean that they develop NAFLD easily." 4. Did you check inflammatory cytokines or blood cell contents in your study? It will be interesting to validate if NAFLD patients have a low level of inflammation since adipokines have been linked to inflammation. • We so appreciate for pointing out this point, but in the present study, these tests were not performed due to financial constraints. But this issue was mentioned in the limitations for future studies. Reviewer 2 � In this study, Ariya et al. seek the association between body composition with risk of NAFLD. The design and procedures of this study sound reasonable and I have no major comments or criticisms for this manuscript. It would be easier for readers to understand if the authors show ROC curves in figures, not Table 3, with p values. Table 2 is confusing and misleading. It looks like the authors show correlation between male and female (e.g., correlation between male left arm fat and female right arm fat), which does not make sense. I think data Table 1 show combined data of male and female, and the authors want to show data for both genders separately. If so, Table 1 is enough to show without Table 2, and if the authors really need to show male and female data separately, format of tables should be same as Table 1, not combined like current Table 2. • We appreciate your valuable comments. Table 3 (now shown as Table 4 in the manuscript) and Figure 1 are reported separately, so it was not possible to display all variables such as "Cut-off Point" in Figure 1. Again, if the reviewer's opinion is to delete this table, we will sincerely delete this table. Besides, it is noteworthy mentioning because of the beneficial recommendation of reviewers, table 2 reanalyzed with the sex-separated and this analysis was performed in tables 2 and 3. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0249223.r002
3 Mar 2021 Decision Letter - Gianfranco D. Alpini, Editor PONE-D-20-34964R1 Assessment of the association between body composition and risk of Non-alcoholic fatty liver PLOS ONE Dear Dr. Reza Homayounfar, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript within 60 days. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Gianfranco D. Alpini Academic Editor PLOS ONE Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: (No Response) Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: As gender difference has been discussed in NAFLD development, the authors may want to include two tables showing data as the table 1 displayed. Reviewer #2: In this study, Ariya et al. seek the association between body composition with risk of NAFLD. I have no further comments. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0249223.r003
Revision 2
8 Mar 2021 Author Response Response to reviewers Dear Editor and Reviewers On behalf of all the authors of the article, I would like to thank the respected editors and reviewers who considered our article worthy of publication in the prestigious journal of Plos ONE and made suggestions to improve the article. We did our best to correct the recommendations and we hope that the article in its current form will acceptable to dear editor and the respected reviewers. Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: (No Response) Reviewer #2: All comments have been addressed ________________________________________ 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ________________________________________ 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ________________________________________ 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ________________________________________ 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ________________________________________ 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: As gender difference has been discussed in NAFLD development, the authors may want to include two tables showing data as the table 1 displayed. Reviewer #2: In this study, Ariya et al. seek the association between body composition with risk of NAFLD. I have no further comments. Considering that changing table number one would cause a significant change in the results section of the article, we decided to make this suggestion of the esteemed reviewer in the form of supplementary tables number one and two. Attachments Attachment Submitted filename: Response to Reviewers 2.docx https://doi.org/10.1371/journal.pone.0249223.r004
15 Mar 2021 Decision Letter - Gianfranco D. Alpini, Editor Assessment of the association between body composition and risk of Non-alcoholic fatty liver PONE-D-20-34964R2 Dear Dr. Reza Homayounfar, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Gianfranco D. Alpini Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Thanks for your response. It is okay to have the table published as supplementary information. It is acceptable. Reviewer #2: In this study, Ariya et al. seek the association between body composition with risk of NAFLD. I have no further comments. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No https://doi.org/10.1371/journal.pone.0249223.r005
Formally Accepted
19 Mar 2021 Acceptance Letter - Gianfranco D. Alpini, Editor PONE-D-20-34964R2 Assessment of the association between body composition and risk of Non-alcoholic fatty liver Dear Dr. Homayounfar: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Gianfranco D. Alpini Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0249223.r006

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