PONE-D-20-12246

Hepatitis C prevalence in Denmark in 2016

- an updated estimate using multiple national registers

PLOS ONE

Dear Dr. Christensen,

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Yury E Khudyakov, PhD

Academic Editor

PLOS ONE

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4.Thank you for stating the following in the Financial Disclosure section:

'The study was supported by an unrestricted grant from MSD Denmark

URL: https://www.msd.dk/home

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.'

We note that you received funding from a commercial source: MSD Denmark

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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?

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: Partly

Reviewer #2: No

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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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

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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

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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 paper is of very poor value from the scientific point of view. The estimate of the proportion of subjects with undiagnosed CHC is affected by important biases: prisoners aren't representative of the general population, indeed findings lack of external validity; data from sera collected more than 20 years ago (1998-2000) are extremely out-dated.

Furthermore, the epidemiological data presented are obsolete because, starting from 2014, the epidemiological context has completely changed following the new direct-acting oral antiviral therapies (DAA) which, with a high sustained viral response (> 95%) and the consequent increase in treatments, have led to a faster decline of chronic hepatitis C prevalence globally.

HCV infection is mostly asymptomatic end random population-based surveys may provide accurate figures. Several national surveys have been performed in France, Spain, Italy, and U.S.A. over the last few years. None of them has been commented in the Discussion and reported in the References.

Reviewer #2: PONE-D-20-12246

The authors used a capture recapture method to estimate the population living with HCV in Denmark in the year 2016. The concept of this study is of value and the results will contribute to the literature. However, I have some comments regarding the analysis, and the content of the study.

I have below a few comments and suggestions that may improve the readability and understandability of the article.

Major comments:

1- In the method section, the first paragraph placement is confusing (line 82-line 86). I would suggest placing this paragraph after the data sources listing since this is highlighting the indicator used for the recapture stage.

2- In the Results section, the 2nd paragraph was confusing and hard to follow. The excluded 1,292 patients from the hospital register should be mentioned in the first paragraph where the authors are listing how they ended up with the number of patients included in the analysis (Line 190-198).

3- Also, I don’t understand how these patients were still counted since they didn’t meet the case definition mentioned in the methods section above: "1,292 who had either negative antiHCV or HCV-RNA results and/or had chronic hepatitis B (ICD10 code 18.1) with no signs of HCV coinfection according to the other source registers."

Minor comments:

1- Method section line 96, the word "included" is missing: " Since 1995, it also included all 97 hospital outpatient and emergency department visits

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Reviewer #1: Yes: Filomena Morisco

Reviewer #2: No

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Hepatitis C prevalence in Denmark in 2016

- an updated estimate using multiple national registers

PONE-D-20-12246R1

Dear Dr. Christensen,

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.

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Kind regards,

Yury E Khudyakov, 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 #2: All comments have been addressed

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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 #2: Yes

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

Reviewer #2: Yes

**********

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

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

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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 #2: Yes

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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 #2: (No Response)

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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 #2: No