Dear Dr. Sander,

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.

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We look forward to receiving your revised manuscript.

Kind regards,

Yury E Khudyakov, PhD

Academic Editor

PLOS ONE

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Additional Editor Comments:

Your manuscript was reviewed by two experts in the field. Both identified significant problems in your submission. Please review the attached comments and provide point-by-point responses.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Partly

Reviewer #2: Yes

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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

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: This article iis covering an important topic on HCV. Unfortunatelly it is not easily readable, especially the abstract and introduction is not very attractive for the reader. I do not see much impact of this article to the future. On the other hand many known or expected facts have been confirmed.

Other comments and questions concerning specific part of the text which should be corrected or explained:

- line 40+397: Do you mean liver-related mortality?

- SVR was mentioned several times before you explained it (line 107) and the abbreviation is translated in two different ways in the article (sustained viral clearance - most cases and sustained virologic response- line 289 and 311). I don't think sustained viral clearance is the correct term because both European and American guidelines use the term sustained virologic response.

- line 98 and further: ICES - Is there any explanation of this abbreviation?

- line 156+165: I would suggest HCV RNA positivity instead of RNA diagnosis

- line 160-161: Why 5 % of patients had HCC at diagnosis if almost 80 % did not have cirrhosis? How was the cirrhosis diagnosis made?

- line 162: Why only 47 % recieved HCV treatment?

- line 385+404: Do you mean liver-related death?

- line 402: Dot missing at the end of the sentence.

Reviewer #2: The article presents a very interesting work, with a high number of patients about the impact of SVR obtained in the reduction of liver-death, but I have some issues that must be adressed:

1) The authors must describe very well in which manner they mantain the follow-up. Was only a clinical examination, or they performed an ultrasound, maybe an evluation of liver fibrosis and steatosis after SVR was obtaine?

2) The authors must explain if there is an impact of asociation of liver steatosis after SVR was obtained.

3) Liver steatosis was found to be an important factor that can cause advaned liver disease after SVR, due to the changes of beheaviour in patients (more food-intake, appereances of metabolic syndrome and T2DM) which can cause liver-trelated events and death in time. How was the impact of liver steatosis in those subjects, after SVR was obtained?

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what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: Yes:  Robert Nastasa

**********

[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.]

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Dear Dr. Sander,

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.

==============================

Your revised manuscript was reviewed by two original reviewers. Although one was satisfied with your modifications, the other pointed at a few remaining problems.  

==============================

Please submit your revised manuscript by Sep 26 2025 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.

• 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 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,

Yury E Khudyakov, PhD

Academic Editor

PLOS ONE

Journal Requirements:

If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

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.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #1: Partly

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: I Don't Know

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

**********

Reviewer #1: The authors improved the readabilty of abstract and introduction and corrected mistakes. The authors implied most of the reccomendations but forgot to correct SVR in the supplementary materials and I found some more flaws in the text.

These mistakes or inaccuracies I suggest correcting:

Please stick to HCV RNA positivity, it is a more proper term than RNA positivity (line 175, 185...).

Explain N in bellow the tables (it was deleted in some table descriptions (eg. table 2,3,4) but I think it stould stay there.

Throughout some tables HBsAG is written but both EASL and AASLD guidelines use abbreviation HBsAg (not capital G).

Throughout some tables abbreviation yrs. is used but not explained. Either explain it in the description of the table or write years as in the table 1.

Throughout some tables abbreviation ref. is used but not explained in the description of the tables.

Line 46: delete one bracket in )) = )

Line 104: formerly known or currently known as the Institute for Clinical Evaluative Sciences?

Line 201: DAA era should be DAA-era if you want to stick to the terminology with dash which is used further in the text

Line 205: vs - dot is missing - vs.

Line 233: space is missing after vs.

Line 243: dash is missing in pre-DAA-era

Line 276: CI: instead of C,I

Line 284+312: Time-to-liver-related mortality is not clear. There are too many dashes and I'm not sure if I understand the meaning of this term.

Line 309: Do you mean higher incidence of liver-related death?

Line 372: other word than realise would be more suitable

Line 393: What is the meaning of PHO HCV testing?

Line 414: liver-related death

Line 426: correct liver-realted death to liver-related death

Supplementary materials:

1. SVR is not corrected in the description of the abbreviations, it states sustained viral clearance.

2. All tables are named S1-S7 but bellow the tables there is written table A1-A7 instead of S1-S7. In the main text all the tables are named only above the table but bellow the tables there is only the description but not Table xxx and the description. Please unify this and correct.

Table S7: Sudy Cohort means study cohort?

Reviewer #2: The article has been improved with the recommendations that I made for the first manuscript, and now can be accepted for publication.

**********

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

Effect of sustained virologic response on liver-related mortality among individuals living with hepatitis C by treatment era: a population-based retrospective cohort study

PONE-D-25-05248R2

Dear Dr. Sander,

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.

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Kind regards,

Yury E Khudyakov, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: