Comparing the controlled attenuation parameter using FibroScan and attenuation imaging with ultrasound as a novel measurement for liver steatosis

Po-Ke Hsu; Li-Sha Wu; Wei-Wen Su; Pei-Yuan Su; Yang-Yuan Chen; Yu-Chun Hsu; Hsu-Heng Yen; Chia-Lin Wu

doi:10.1371/journal.pone.0254892

Peer Review History

Original SubmissionNovember 29, 2020
10 Mar 2021 Decision Letter - Domokos Máthé, Editor PONE-D-20-37505 A prospective comparative study of the controlled attenuation parameter using FibroScan and attenuation imaging with ultrasound in evaluating liver steatosis PLOS ONE Dear Dr. Hsu, 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 by Apr 09 2021 11:59PM. 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, Domokos Máthé 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. Thank you for stating in the text of your manuscript "all participants signed an informed consent form for this study". Please also add this information to your ethics statement in the online submission form. 3. In your Methods section, please provide additional information about the participant recruitment method and the demographic details of your participants. Please ensure you have provided sufficient details to replicate the analyses such as: a) a statement as to whether your sample can be considered representative of a larger population, and b) a description of how participants were recruited. 4. We noticed you have some minor occurrence of overlapping text with the following previous publications, which needs to be addressed: - https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0182784 - https://researchportal.bath.ac.uk/en/publications/endothelin-receptor-aa-regulates-proliferation-and-differentiatio-2 In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. 5. Thank you for stating the following financial disclosure: "NO - Include this sentence at the end of your statement: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." At this time, please address the following queries: Please clarify the sources of funding (financial or material support) for your study. List the grants or organizations that supported your study, including funding received from your institution. State what role the funders took in the study. If the funders had no role in your study, please state: “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.” If any authors received a salary from any of your funders, please state which authors and which funders. If you did not receive any funding for this study, please state: “The authors received no specific funding for this work.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 6. Please amend your list of authors on the manuscript to ensure that each author is linked to an affiliation. Authors’ affiliations should reflect the institution where the work was done (if authors moved subsequently, you can also list the new affiliation stating “current affiliation:….” as necessary). 7. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. [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: I Don't Know 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: No ****** 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: Yes 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: The authors describe a comparative study of controlled attenuation parameter using FibroScan and attenuation imaging with ultrasound in liver steatosis. The topic of the work is interesting and serves a good base to detect liver steatosis by noninvasive manner. For these reason, the manuscript is suitable for publication after revision of some sections, reported here: Minor revision: I missed the two different investigated techniques from the keywords. The references in the main text from 10 to 19 are missing. At row 82 there is a mistyping by the numbers of inclusion criteria. At row 84 there is an extra ‘s’. The number of excluded patients should move from the material and method section to the result part. The Liver biopsy section in the material and methods is superficial. There is not enough information about the applied technique. Any other case, a reference article should be inserted which describes the details of biopsy and staining. There is a mistyping at row 114 dB/cm/MHz. At row 125 the authors write about three groups but there are 4 different ones in parenthesis. The Fig 2 seems a little bit over-explained. At row 155 ATI definition is missing. Major revision: The introduction part contains detailed description (18 lines long) about the steatosis and the gold standard liver biopsy. But there are only 2-2 sentences about the compared techniques. This part should be extended with much more information related to these techniques. At the last paragraph of introduction the authors mention there are other detection methods than CAP and ATI for the diagnosis of steatosis but the relevant references are missing. The image quality of Fig 4 and Fig 5 should be increased. The Fig 4 legend is just a simple sentence of the result. It should contain a title and at least one descriptive sentence. The cohesion power is missing from the discussion section. The consecutive paragraphs are independent from each other. The fourth paragraph would be more appropriate at the introduction part. In the fifth paragraph of discussion, without any introduction or background information there is a comparison with proton-density fat fraction based MRI. The conclusion is too short and not so demonstrative. Other questions: How could you define the success rate and effective shot by the US scans? What does effective data point mean? Reviewer #2: This is a concise paper with the advantage of easily reading the results and judging the significance. A merit of the paper is the accompanying rather detailed patient data as well as the rigorous statistics. There are a number of important concerns, though, which are to be addressed. I do not list all of them one by one, some are issue types, and it is expected that the authors improve all instances of these types. Data availability should be stated in the methods section. Page 2 and Page 13 "No study to date has confirmed the clinical utility of...". This is clearly wrong. There are a number of studies recently published 2020 and 2021. Please include them. With these, the purpose of this study should be specified in more detail. Also your study should be compared to all these. Page 4 "is invasive and prone to triggering complications such as pain..." etc. Reference citing required, and also to all similar statements, that refer to clinical "facts". Page 7 "to make the statistic significant". Determining the unit and display multiplier has nothing to do with significance, please correct the sentence. Page 14a "same from a previous study". Need to cite the previous study. Page 14b "there are several limitations". The reader will need numerical estimation of liver steatosis diagnosis errors coming from obese patients. Cite a study with clinical data, CAP e.g., and/or repeat with a couple of non-obese patients with negative steatosis at least, so that a baseline can be shown: either as non-confounding, or establishing correction factors with subdermal fat amount. ****** 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.0254892.r001
Revision 1
10 Apr 2021 Author Response Dear Editor, We appreciate your editorial comments, as well as those of the reviewers, concerning our manuscript. Based on these comments, we have made several revisions to our manuscript, which is resubmitted for your consideration. If there is anything needing to be further improved, please do not hesitate to inform us at your earliest convenience. Your assistance is highly appreciated. We look forward to your message. The followings are point-by-point responses to the comments. All authors thank the reviewer’s suggestions. Your assistance is highly appreciated. Journal 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 Response: All authors thank the reviewer’s suggestions. We have tried our best to confirm that the format complies with the regulations. Thank you for your advice if there are errors. --------------------------------------------------------------------------------------------------------------------- 2. Thank you for stating in the text of your manuscript "all participants signed an informed consent form for this study". Please also add this information to your ethics statement in the online submission form. Response: All authors thank the reviewer’s suggestions. We will add this information to my ethics statement in the online submission form. --------------------------------------------------------------------------------------------------------------------- 3. In your Methods section, please provide additional information about the participant recruitment method and the demographic details of your participants. Please ensure you have provided sufficient details to replicate the analyses such as: a) a statement as to whether your sample can be considered representative of a larger population, and b) a description of how participants were recruited. Response: All authors thank the reviewer’s suggestions. Thank you for your comments. We have added the participant recruitment method to the article and adding a description of how participants were recruited . We added on “The method of participant recruitment is the notification of liver biopsy from the hospital during this period. After the patient's consent signed, this will be included in the study.” in Row 123- 125, page 7, for participant recruitment method, and added on “Demographic details of the participants show that they are all Asians, and living in central Taiwan mainly in the Changhua county.” in Row 127- 128, page 7for demographic details of participants. --------------------------------------------------------------------------------------------------------------------- 4. We noticed you have some minor occurrence of overlapping text with the following previous publications, which needs to be addressed: - https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0182784 - https://researchportal.bath.ac.uk/en/publications/endothelin-receptor-aa-regula tes-proliferation-anddifferentiatio-2 In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed. Response: All authors thank the reviewer’s suggestions. Thank you for your comments. We have revised and strengthened related paragraphs, such as the following: 1. We changed the title of “Compared the Ccontrolled attenuation parameter using FibroScan with and attenuation imaging with ultrasound as an novel measurement for evaluating liver steatosis” in Row 2-3, page 1. 2. changed the duplicated text “reliable” to “novel” in Row 2, page 1. 3. changed the duplicated text and added on “According to the Clinical Practice Guidelines from European Association for the Study of the Liver (EASL), the golden standard for diagnosis and evaluation fatty liver is liver biopsy [7]. Currently, the gold-standard technique for diagnosing and evaluating liver steatosis is liver biopsy; In addition to distinguishing the presence or absence of fatty liver through liver biopsy, non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) can only be distinguished through liver biopsy. Hhowever, this procedureapproach is invasive and prone to triggering complications, such as pain, bleeding, and infection, and its results may be delayed due to the need to generate pathological reports.”, and we also cited the journal of “https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0182784 in Row 77- 82, page 5 4. changed the duplicated text and added on “Some studies have shown that using an ultrasound scanner such as FibroScan® (Echosens, Paris, France) together with the controlled attenuation parameter (CAP) to measure the amount of ultrasound attenuation can quantitatively and accurately assess the severity of the liver steatosis fatty liver in concordance with liver biopsy [8]. However, FibroScan® is not an imaging device and cannot perform B-mode ultrasound assessments at the same time” in Row 89-95, page 6. --------------------------------------------------------------------------------------------------------------------- 5. Thank you for stating the following financial disclosure: "NO - Include this sentence at the end of your statement: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." At this time, please address the following queries: a. Please clarify the sources of funding (financial or material support) for your study. List the grants or organizations that supported your study, including funding received from your institution. b. State what role the funders took in the study. If the funders had no role in your study, please state: “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.” c. If any authors received a salary from any of your funders, please state which authors and which funders. d. If you did not receive any funding for this study, please state: “The authors received no specific funding for this work.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf. Response: We will add on the text ”The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript” within the cover letter. Thanks for your suggestions. --------------------------------------------------------------------------------------------------------------------- 6. Please amend your list of authors on the manuscript to ensure that each author is linked to an affiliation. Authors’ affiliations should reflect the institution where the work was done (if authors moved subsequently, you can also list the new affiliation stating “current affiliation:….” as necessary). 7. Please include captions for your Supporting Information files at the end of your manuscript, and update any intext citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. Response: We will add on the text and make it more perfect. Thanks for your suggestions. --------------------------------------------------------------------------------------------------------------------- Reviewer: 1 The authors describe a comparative study of controlled attenuation parameter using FibroScan and attenuation imaging with ultrasound in liver steatosis. The topic of the work is interesting and serves a good base to detect liver steatosis by noninvasive manner. For these reason, the manuscript is suitable for publication after revision of some sections, reported here: Minor revision: I missed the two different investigated techniques from the keywords. Response: All authors thank the reviewer’s suggestions. Thank you for your comments. We added on the keywords as follow “controlled attenuation parameter; attenuation imaging” in Row 62-63, page 4. --------------------------------------------------------------------------------------------------------------------- The references in the main text from 10 to 19 are missing. Response: We are very sorry, this is our typesetting negligence, and we will make up the relevant reference. --------------------------------------------------------------------------------------------------------------------- At row 82 there is a mistyping by the numbers of inclusion criteria. Response: Thank you for your advice, this is our major mistake and made the following revisions: (2) signed the informed consent form to (3) signed the informed consent form in Row 125, page 7 --------------------------------------------------------------------------------------------------------------------- At row 84 there is an extra ‘s’. Response: Thank you for your advice, this is our major mistake and made the correction in Row 122, page 7 -------------------------------------------------------------------------------------------------------------------- The number of excluded patients should move from the material and method section to the result part. Response: Thank you for your advice, this is our major mistake and made the correction. We moved the excluded patient number to the result in Row 188- 192, page 10 in Result section. -------------------------------------------------------------------------------------------------------------- The Liver biopsy section in the material and methods is superficial. There is not enough information about the applied technique. Any other case, a reference article should be inserted which describes the details of biopsy and staining. Response: Thank you for your advice, this is our major negligence. We have added some discussion and cited related articles of liver biopsy in Row 133- 138, page 8 --------------------------------------------------------------------------------------------------------------------- There is a mistyping at row 114 dB/cm/MHz. Response: Thank you for your advice, this is our major mistake and made the correction in Row 161, page 9 --------------------------------------------------------------------------------------------------------------------- At row 125 the authors write about three groups but there are 4 different ones in parenthesis. Response: Thank you for your advice, this is our major mistake and made the correction from three groups to four groups in Row 171, page 9 --------------------------------------------------------------------------------------------------------------------- The Fig 2 seems a little bit over-explained. Response: Thank you for your advice, this is our major mistake and made the correction from “Fig 2. Study flowchart” without figure Legends, just entitled with the “Fig 2. Study flowchart”. in Row 193, page 10 --------------------------------------------------------------------------------------------------------------------- At row 155 ATI definition is missing. Response: Thank you for your advice, this is our major mistake and made the correction with adding “attenuation imaging” for ATI, in Row 208, page 13 in Table 1 legends. --------------------------------------------------------------------------------------------------------------------- Major revision: The introduction part contains detailed description (18 lines long) about the steatosis and the gold standard liver biopsy. But there are only 2-2 sentences about the compared techniques. This part should be extended with much more information related to these techniques. Response: Thanks for your suggestion, we will revise the proportion of these two checks in the article. We added on the CAP at in Row 89-94, page 6, in introduction section. We also added on the ATI in Row 96- 105, page 6 in introduction section. --------------------------------------------------------------------------------------------------------------------- At the last paragraph of introduction the authors mention there are other detection methods than CAP and ATI for the diagnosis of steatosis but the relevant references are missing. Response: Thank you for your advice, this is our major mistake and made the correction with added on the “reference 25 to 27” showed MRI for liver steatosis with “Another non-invasive tool is magnetic resonance imaging proton density fat fraction (MRI-PDFF), which can accurately quantify liver steatosis and provide the value of imaging diagnosis [24]. However, the cost of the instrument and the inconvenient operation are also disadvantages “ in Row 106- 109, page 6 --------------------------------------------------------------------------------------------------------------------- The image quality of Fig 4 and Fig 5 should be increased. Response: Thank you for your advice, we will improved the quality of the Fig 4 and Fig 5. -------------------------------------------------------------------------------------------------------------------- The Fig 4 legend is just a simple sentence of the result. It should contain a title and at least one descriptive sentence. Response: Thank you for your advice, this is our major mistake and made the correction. First, we added the “We used Pearson's correlation coefficient for ATI and CAP to confirm whether they are positively related” in Row 177- 179, page 10. In Statistic section. Second, We added on a descriptive sentence with “ATI and CAP were positively correlated (r = 0.8111; p < 0.05)” and entitled with “The association between ATI and CAP” in Row 232- 233, page 13 in Fig 4. --------------------------------------------------------------------------------------------------------------------- The cohesion power is missing from the discussion section. The consecutive paragraphs are independent from each other. The fourth paragraph would be more appropriate at the introduction part. Response: Thank you for your advice, this is our major mistake and made the correction. We will move the text of the fourth paragraph in discussion section to introduction part as ” Basing on two-dimensional images in daily ultrasound examination within less than 2 minutes performing time, ATI showed the convenience in routine screening of liver steatosis[23]. As compared with CAP, ATI's advantage is the existence of an ultrasonic inspection mode, so there is no need to arrange for additional equipment for examinations [24]”, in Row 101- 105, page 6. --------------------------------------------------------------------------------------------------------------------- In the fifth paragraph of discussion, without any introduction or background information there is a comparison with proton-density fat fraction based MRI. Response: Thank you for your advice, this is our major mistake and added the MRI-PDFF in introduction with “ Another non-invasive tool is magnetic resonance imaging proton density fat fraction (MRI-PDFF), which can accurately quantify liver steatosis and provide the value of imaging diagnosis [25]. However, the cost of the instrument and the inconvenient operation are also disadvantages [26] [27].”and discussion section with “ A study showed that MRI-PDFF with AUROC for classifying steatosis grades 0 vs. 1–3, 0–1 vs. 2–3, and 0–2 vs. 3 were 0.98, 0.91, and 0.90, respectively. in Row 293- 294, page 17 --------------------------------------------------------------------------------------------------------------------- The conclusion is too short and not so demonstrative. Response: Thank you for your advice, this is our major mistake and made the correction with “ATI has a higher AUROC values in different grading of liver steatosisthan CAP demonstrating ATI’s excellent and accurate diagnostic ability. . In the future, ATI may be a promising technique for liver steatosis screening.” in Row 305- 310, page 17 --------------------------------------------------------------------------------------------------------------------- Other questions: How could you define the success rate and effective shot by the US scans? Response: Thank you for your questions. We defined the “ a success rate of at least 60% was achieved” in ATI measurement method : Fully meet the following conditions (1) at least five effective values were collected, (2) R2 value of 0.9 or greater at every single data point was recorded, and (3) the interquartile range was less than 30% of the median ATI. If the technician completes an inspection and fails to meet any of the three items, it is considered a failure. If the success rate is not higher than 60%, the inspection case must be excluded. --------------------------------------------------------------------------------------------------------------------- What does effective data point mean? Response: Thank you for your questions. The text does not express the meaning very accurately, so we changed it from "at least five effective data points” to “ at least five effective values “ at in Row 162, page 9. Thank you again for your careful review. --------------------------------------------------------------------------------------------------------------------- Reviewer #2: This is a concise paper with the advantage of easily reading the results and judging the significance. A merit of the paper is the accompanying rather detailed patient data as well as the rigorous statistics. There are a number of important concerns, though, which are to be addressed. I do not list all of them one by one, some are issue types, and it is expected that the authors improve all instances of these types. Data availability should be stated in the methods section. Response: Thank you for your advice. We added on Data availability stating in the methods section. in Row 128, page 7 in method section. ---------------------------------------------------------------------------------------------------------------- Page 2 and Page 13 "No study to date has confirmed the clinical utility of...". This is clearly wrong. There are a number of studies recently published 2020 and 2021. Please include them. With these, the purpose of this study should be specified in more detail. Also your study should be compared to all these. Response: Thank you for your advice. This is obviously our mistake. We made these corrections: 1. delete the “No study to date has confirmed the clinical utility of...". in Row 39, page 3. . 2. Adding the text “ However, there are many studies on ATI and controlled attenuation parameter (CAP) to prove their practicability, but there are few studies comparing these two methods.no study to date has confirmed the clinical utility of this technique. As such, this study compared the controlled attenuation parameter (CAP) gleaned using FibroScan® (Echosens, Paris, France) and ATI for the detection and evaluation of liver steatosis.” in Row 39- 43, page 3. --------------------------------------------------------------------------------------------------------------------- Page 4 "is invasive and prone to triggering complications such as pain..." etc. Reference citing required, and also to all similar statements, that refer to clinical "facts". Response: Thank you for your advice. This is obviously our mistake. We has changed text cited with No.16 reference. in Row 82-83 , page 5. --------------------------------------------------------------------------------------------------------------------- Page 7 "to make the statistic significant". Determining the unit and display multiplier has nothing to do with significance, please correct the sentence. Response: Thank you for your advice. This is obviously our mistake. This is just a unit, we have deleted the redundant words that follow, thank you for your review, in Row 162, page 9. --------------------------------------------------------------------------------------------------------------------- Page 14a "same from a previous study". Need to cite the previous study. Response: Thank you for your advice. This is obviously our mistake. The previous study means our current study data. So, we delete the text and change it to “ This result showed CAP assessment could distinguish different grades of liver steatosis with a significant difference.” in Row 285, page 16. --------------------------------------------------------------------------------------------------------------------- Page 14b "there are several limitations". The reader will need numerical estimation of liver steatosis diagnosis errors coming from obese patients. Cite a study with clinical data, CAP e.g., and/or repeat with a couple of nonobese patients with negative steatosis at least, so that a baseline can be shown: either as non-confounding, or establishing correction factors with subdermal fat amount. Response: Thank you for your advice. This is obviously our mistake. We has mede the correction with “relatively obese patients (in the patients with BMI of 28 kg/m2 or more, CAP has no correlation with actual liver fat percentage) [34]” and cite No. 34 reference in Row 298-299, page 17. Attachments Attachment Submitted filename: Response to reviewer - 1-2021.docx https://doi.org/10.1371/journal.pone.0254892.r002
24 May 2021 Decision Letter - Jee-Fu Huang, Editor PONE-D-20-37505R1 Comparing the controlled attenuation parameter using FibroScan and attenuation imaging with ultrasound as a novel measurement for liver steatosis PLOS ONE Dear Dr. Hsu, 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. Specifically, the following author, James Cheng-Chung Wei Chung Shan Medical University, was added to the revised version. It did not appear to meet the authorship policies unless a specific contribution was made and mentioned by him in the original version, particularly the newly-added author abruptly served as the corresponding author of the manuscript. The Authors should have a clear declaration and signed agreement by all authors for the ethic concern. Otherwise, the authorship should only list the original authors. Please submit your revised manuscript by Jul 08 2021 11:59PM. 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. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Jee-Fu Huang, M.D., Ph.D. 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. Additional Editor Comments (if provided): The following author, James Cheng-Chung Wei Chung Shan Medical University, was added to the revised version. It did not appear to meet the authorship policies unless a specific contribution was made and mentioned in the original version, particularly the newly-added author abruptly served as the corresponding author of the manuscript. The Authors should have a clear declaration and signed agreement regarding it. [Note: HTML markup is below. Please do not edit.] [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.0254892.r003
Revision 2
5 Jul 2021 Author Response Dear Editor, We appreciate your editorial comments, as well as those of the reviewers, concerning our manuscript. Based on these comments, we have made several revisions to our manuscript, which is resubmitted for your consideration. If there is anything needing to be further improved, please do not hesitate to inform us at your earliest convenience. Your assistance is highly appreciated. We look forward to your message. The followings are point-by-point responses to the comments. All authors thank the reviewer’s suggestions. Your assistance is highly appreciated. Journal Requirements: Specifically, the following author, James Cheng-Chung Wei Chung Shan Medical University, was added to the revised version. It did not appear to meet the authorship policies unless a specific contribution was made and mentioned by him in the original version, particularly the newly-added author abruptly served as the corresponding author of the manuscript. The Authors should have a clear declaration and signed agreement by all authors for the ethic concern. Otherwise, the authorship should only list the original authors. Response: After discussing with various authors, the original author group accepted the editor’s kind suggestions. Decided to remove the relevant information of James Cheng-Chung Wei Chung Shan Medical University in order to comply with the ethics of scientific research on Page 1 , Line 6. We also fixed the Author Contributions on Page 18, Line 292. This is our negligence. We are very sorry. Updated with IRB No. 210202 Response: Because this research is being updated and reviewed again this year(2021), the IRB number is updated at this time to more accurately comply with the research ethical basis. Thank you reviewer for the suggestion. We also attach the latest IRB in the attachment to ensure the rigor of the research. We revised the IRB no 210202. at Page 7, Line 118 Attachments Attachment Submitted filename: Response to reviewer 2.docx https://doi.org/10.1371/journal.pone.0254892.r004
7 Jul 2021 Decision Letter - Jee-Fu Huang, Editor Comparing the controlled attenuation parameter using FibroScan and attenuation imaging with ultrasound as a novel measurement for liver steatosis PONE-D-20-37505R2 Dear Dr. Wu, 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, Jee-Fu Huang, M.D., Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): The Authors have sufficiently responded to the comments raised. Reviewers' comments: https://doi.org/10.1371/journal.pone.0254892.r005
Formally Accepted
8 Oct 2021 Acceptance Letter - Jee-Fu Huang, Editor PONE-D-20-37505R2 Comparing the controlled attenuation parameter using FibroScan and attenuation imaging with ultrasound as a novel measurement for liver steatosis Dear Dr. Wu: 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. Jee-Fu Huang Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0254892.r006

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