Increasing liver stiffness is associated with higher incidence of hepatocellular carcinoma in hepatitis C infection and non-alcoholic fatty liver disease–A population-based study

Perica Davitkov; Kyle Hoffman; Yngve Falck-Ytter; Brigid Wilson; Gjorgje Stojadinovikj; Donald D. Anthony; Stanley Martin Cohen; Gregory Cooper

doi:10.1371/journal.pone.0280647

Peer Review History

Original SubmissionMay 17, 2022
26 Oct 2022 Decision Letter - Yuh-Shin Chang, Editor Transfer Alert This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present. PONE-D-22-13686Increasing liver stiffness is associated with higher incidence of hepatocellular carcinoma – a population-based studyPLOS ONE Dear Dr. Hoffman, 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. ACADEMIC EDITOR:Your manuscript has been assessed by our reviewers. They have raised a number of points which we believe would improve the manuscript and may allow a revised version to be published in PLOS ONE. Please submit your revised manuscript by Dec 10 2022 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: https://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, Yuh-Shin Chang, MD, PhD 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 amend your current ethics statement to include the full name of the ethics committee/institutional review board(s) that approved your specific study. 3. In ethics statement in the manuscript and in the online submission form, please provide additional information about the patient records/samples used in your retrospective study. Specifically, please ensure that you have discussed whether all data/samples were fully anonymized before you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent. If patients provided informed written consent to have data/samples from their medical records used in research, please include this information. 4. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. 5. Thank you for stating the following in your Competing Interests section: None of the authors reports conflict of interest Please complete your Competing Interests on the online submission form to state any Competing Interests. If you have no competing interests, please state "The authors have declared that no competing interests exist.", as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now This information should be included in your cover letter; we will change the online submission form on your behalf. 6. 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 Reviewer #3: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: 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 Reviewer #3: 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: Yes Reviewer #2: Yes Reviewer #3: No ****** 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: This is a retrospective study assessing TE stiffness relation with HCC in patients with HCV or NASH. The following suggestions should be considered: 1. In the abstract it should be stated the duration of the mean followed up for patients. 2. To include p-value for characteristics difference in table 1. 3. To include a parapragh on the effect of HCV treatment on the population as part of the discussion. Reviewer #2: The authors analyzed the rates of HCC in both HCV and NAFLD patients. They concluded that HCC incidence increased with higher TE liver stiffness measures in both HCV and NAFLD. The experiments were conducted properly. The conclusions was solidly based on the data analyzed. Reviewer #3: In this manuscript, Davitkov et al. present the findings of increased incidence of hepatocellular carcinoma in non-alcoholic fatty liver disease (NAFLD) and hepatitis C virus (HCV) infected patients. Overall, the paper is well written and grammatically correct. However, the clear rationale for conducting the study and the novelty is lacking. There are concerns about the results which require addressing before the manuscript can be considered for publication. Results: 1. In Table 1, there are too many gridlines in the table. For example, you have divided the heading “Race” into 4 rows including white, black, other, and unknown. You need to hide the gridlines between each group, indent, and merge the 4 subheadings into one row. This will make the table easier for readers to read. Moreover, the abbreviations in the table should be defined in the footnotes. 2. If I am not mistaken, your study population is divided into 2 study groups, HCV and NAFLD. Increased transient elastography was shown, indicating an increased incidence of HCC. Do you have data which shows that patients with both HCV and NAFLD have a higher incidence rate ratio for developing HCC? 3. Considering your study results, I recommend changing your research title by adding both HCV and NAFLD to your article title. This will enable readers to easily understand why liver stiffness can result in HCC. ****** 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 Reviewer #3: 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.0280647.r001
Revision 1
29 Nov 2022 Author Response 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 Updated style and file naming to meet PLOS one requirements. 2. Please amend your current ethics statement to include the full name of the ethics committee/institutional review board(s) that approved your specific study. Changed within the body of the manuscript to reflect approval through the VA Northeast Ohio System Research Office and the VA Innovation and Research Review System. 3. In ethics statement in the manuscript and in the online submission form, please provide additional information about the patient records/samples used in your retrospective study. Specifically, please ensure that you have discussed whether all data/samples were fully anonymized before you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent. If patients provided informed written consent to have data/samples from their medical records used in research, please include this information. Data was collected and stored with full Protected Health Information (PHI) on VA servers behind a VA fire wall. For data analysis, identifiers were removed and only coded data was analyzed. Given that data is de-identified and fully anonymized, the IRB committee waived the requirement for informed consent and HIPPA Authorization. The manuscript was updated to reflect this. 4. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. Grant info: UH Cleveland Medical Center, Seidman Cancer Center- small internal award for large database studies. Oracle Grant PTAEO: 17572.01.P0534.xxxxx.49275. When we resubmit, the funding info/financial disclosures will all reflect this. 5. Thank you for stating the following in your Competing Interests section: None of the authors reports conflict of interest Please complete your Competing Interests on the online submission form to state any Competing Interests. If you have no competing interests, please state "The authors have declared that no competing interests exist.", as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now This information should be included in your cover letter; we will change the online submission form on your behalf. This was added to the cover letter in a competing interests section. 6. 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. Added. 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 Reviewer #3: Yes ________________________________________ 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: 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 Reviewer #3: 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: Yes Reviewer #2: Yes Reviewer #3: No Not sure of the specific concerns from reviewer #3 but any further concerns addressed below. ________________________________________ 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: This is a retrospective study assessing TE stiffness relation with HCC in patients with HCV or NASH. The following suggestions should be considered: 1. In the abstract it should be stated the duration of the mean followed up for patients. Added to abstract. 2. To include p-value for characteristics difference in table 1. P values added to table 1. 3. To include a paragraph on the effect of HCV treatment on the population as part of the discussion. In the third paragraph of the discussion section “HCC in the HCV subgroup”, we discuss the potential effects of HCV treatment on fibrosis. We also added a line about how treatment of HCV has been previously shown to reduce the risk of HCC and corelate with our results. Reviewer #2: The authors analyzed the rates of HCC in both HCV and NAFLD patients. They concluded that HCC incidence increased with higher TE liver stiffness measures in both HCV and NAFLD. The experiments were conducted properly. The conclusions was solidly based on the data analyzed. Reviewer #3: In this manuscript, Davitkov et al. present the findings of increased incidence of hepatocellular carcinoma in non-alcoholic fatty liver disease (NAFLD) and hepatitis C virus (HCV) infected patients. Overall, the paper is well written and grammatically correct. However, the clear rationale for conducting the study and the novelty is lacking. There are concerns about the results which require addressing before the manuscript can be considered for publication. The rationale for the study is, to date, there is not data on the risk for HCC (and thus whether surveillance is needed) in non-cirrhotic patients with advanced fibrosis. This was made more clear in the revised manuscript. Results: 1. In Table 1, there are too many gridlines in the table. For example, you have divided the heading “Race” into 4 rows including white, black, other, and unknown. You need to hide the gridlines between each group, indent, and merge the 4 subheadings into one row. This will make the table easier for readers to read. Moreover, the abbreviations in the table should be defined in the footnotes. Fixed gridlines to make table appear cleaner. Abbreviations now in legend. 2. If I am not mistaken, your study population is divided into 2 study groups, HCV and NAFLD. Increased transient elastography was shown, indicating an increased incidence of HCC. Do you have data which shows that patients with both HCV and NAFLD have a higher incidence rate ratio for developing HCC? This data was not collected – in the NAFLD population, those with HCV were excluded. Though no specific exclusion was made for those with hepatitis C who may have had concurrent NAFLD, no specific data on patients with both pathologies was collected. 3. Considering your study results, I recommend changing your research title by adding both HCV and NAFLD to your article title. This will enable readers to easily understand why liver stiffness can result in HCC. Added. Attachments Attachment Submitted filename: Response To Reviewers.docx https://doi.org/10.1371/journal.pone.0280647.r002
27 Dec 2022 Decision Letter - Yuh-Shin Chang, Editor PONE-D-22-13686R1Increasing liver stiffness is associated with higher incidence of hepatocellular carcinoma in hepatitis C infection and non-alcoholic fatty liver disease – a population-based study PLOS ONE Dear Dr. Hoffman, 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 Feb 10 2023 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: https://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, Yuh-Shin Chang, MD, PhD Academic Editor PLOS ONE Additional Editor Comments (if provided): Thank you for this expeditious revision. Your manuscript has been assessed by our reviewers. They have raised many points which we believe would improve the manuscript and may allow a revised version to be published. [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: All comments have been addressed Reviewer #3: (No Response) ******** 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 #3: Partly ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #3: 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 #3: 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 #3: No ****** 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 to the authors for following previous suggestions. All my previous comments have been addressed in the current draft. Reviewer #3: Results: 1. In Table 1, you put the description of abbreviations and statistical methods in the title. Please transfer this part to the footnote following Table 1. Besides, in Table 1, you missed the units for many variables. For example, “Age at TE” should be “Age at TE (years).” 2. In Table 2, please spell out the terms that the abbreviations stand for (ETOH, BMI, DM, etc.) in the footnote. 3. In addition, we would appreciate your responses indicated by “Reply: Thanks for your suggestions or Thanks for ……” Otherwise, we cannot easily recognize where your point-by-point answers begin. 4. In your supplementary Table S1, what does “%” indicate in “ICD9s for HCV: '070.41%…’”? ICD9 or ICD10 codes do not use the % symbol. 5. Anyway, I hope you can improve the editing quality of the table or figure design. I suggest reviewing some previous published articles for examples. ****** 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 #3: 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.0280647.r003
Revision 2
29 Dec 2022 Author Response Reviewer #1: Thanks to the authors for following previous suggestions. All my previous comments have been addressed in the current draft. Reviewer #3: Results: 1. In Table 1, you put the description of abbreviations and statistical methods in the title. Please transfer this part to the footnote following Table 1. Besides, in Table 1, you missed the units for many variables. For example, “Age at TE” should be “Age at TE (years).” Reply: Thanks for your suggestion. We have moved the abbreviations to a footnote following table 1. In the footnote, we also added explanations of abbreviations: kPa and kg/m2. In addition, we added units to “Age at TE” and “BMI at TE”. 2. In Table 2, please spell out the terms that the abbreviations stand for (ETOH, BMI, DM, etc.) in the footnote. Reply: Thanks for your suggestion. We added a footnote following table 2 with abbreviations. 3. In addition, we would appreciate your responses indicated by “Reply: Thanks for your suggestions or Thanks for ……” Otherwise, we cannot easily recognize where your point-by-point answers begin. Reply: Thanks for this note. All replies to this revision request are formatted this way. 4. In your supplementary Table S1, what does “%” indicate in “ICD9s for HCV: '070.41%…’”? ICD9 or ICD10 codes do not use the % symbol. Reply: Thanks for your suggestion. We have removed the percent symbols – they were likely a vestige of the way the data was extracted from the database. 5. Anyway, I hope you can improve the editing quality of the table or figure design. I suggest reviewing some previous published articles for examples Reply: Thanks for your comment. I reviewed recent articles and changed the formatting/text of all of the tables. As far as the figures, I’m not sure what would increase the editing quality, but happy to adjust anything as needed! Attachments Attachment Submitted filename: Response To Reviewers (2).docx https://doi.org/10.1371/journal.pone.0280647.r004
5 Jan 2023 Decision Letter - Yuh-Shin Chang, Editor Increasing liver stiffness is associated with higher incidence of hepatocellular carcinoma in hepatitis C infection and non-alcoholic fatty liver disease – a population-based study PONE-D-22-13686R2 Dear Dr. Hoffman, 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, Yuh-Shin Chang, MD, PhD 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 #3: 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 #3: Partly ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #3: 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 #3: 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 #3: 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 #3: Most parts of my concerns have been addressed in the current draft. The authors should learn more from experienced researchers or published articles to improve the presentation of data and the quality of tables or figures. ****** 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 #3: No ******** https://doi.org/10.1371/journal.pone.0280647.r005
Formally Accepted
10 Jan 2023 Acceptance Letter - Yuh-Shin Chang, Editor PONE-D-22-13686R2 Increasing liver stiffness is associated with higher incidence of hepatocellular carcinoma in hepatitis C infection and non-alcoholic fatty liver disease – a population-based study Dear Dr. Hoffman: 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. Yuh-Shin Chang Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0280647.r006

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