PONE-D-19-18755

Liver transplantation in patients with a history of migration – a German single center comparative analysis

PLOS ONE

Dear Bucher,

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:

Intesting manuscript which was appreciated by both expert reviewers. They also came with constructive comments to improve the paper, and points that need to be clarified before we can consider publication.

Please address all issues in a point-by-point response.

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

We would appreciate receiving your revised manuscript by Sep 10 2019 11:59PM. When you are 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.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Frank JMF Dor, M.D., Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

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

http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

1. Please amend your current ethics statement to address the following concerns: Please explain why was written consent was not obtained, how you recorded/documented participant consent, and if the ethics committees/IRBs approved this consent procedure.

2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: 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: This is an extremely interesting paper looking at the results of Liver Tx in patients with a history of migration in a German center. This has been found a negative predictor of survival in US and UK cohorts but has not been studied in detail in a continental EU country. Shortlty speaking no difference was found in outcome. The most relevant difference was seen in indication and demographics: more alcoholic cirrhosis in the non migrant population and more viral hepatitis in the migrant group and a younger age at transplant in the migrant group. Authors are to be congratulated to discuss this sometimes controversial subject and for their work and results.

My major comment /question is that the equivalent results in these 2 populations might reflect an adequate patient selection independent of the migratory status. As a corollary question, I was wondering whether the percentage of LTx candidates turned down from transplant (not listed) was the same according to the migratory background? For example the percentage of patients with poor communication capacities was very small in the mig group. Poor communication is a general contraindication for LTx whatever the ethnical background. Was there a higher rate of patients excluded from LTx for poor communication and poor language skills in mig patients?

A note on the juridic aspect of LTx in migrants could be added. I suppose that by law, all registred migrants have access to Transplant and health care in general. The true difficulty is in patients who very recently arrived and are not resident yet or not registred yet. Were the authors confronted with this situation? Could they highlight this problematic? I remember that a few cases of LTx for ALF (I think for mushroom intoxication) in Germany were reported at a transplant meeting in Belgium (BTS) a few years ago with good outcome. Are the authors aware of these cases? Have they been published/reported/publicized (in literature and/or media)? If yes could it be possible to refer to them?

Another difficulty is the access to medications and follow up in case of planned return to a home land without German/European health care. Have the authors been confronted with this scenario and would this play a role in decision-making?

One might argue that german mig born in Germany might represent a lower risk population compared to recently arrived non german citizens? Can authors comment on that?

Within the mig group, german citizens mig did better than non german. However non german mig did equally well compared to non mig patients. What about german citizens mig versus non mig control?

The MV analysis showed no impact of mig status. Did the authors stratify this analysis depending upon the various mig types? German citizens vs non citizens mig etc?

Again congratulations to this team for this study and the results

Best Regards

Jacques Pirenne

Reviewer #2: In this manuscript Bucher et al. investigates the role of recipient history migration on the outcome of liver transplantation in a single center, descriptive cohort study. They did not find differences in outcome between recipient with and without the history of migration.

I read with interest this manuscript and I have few comments and questions to the authors:

The authors perform extensive statistical analysis on this rather small group of patients as 67 patients out of 358 patients had a history of migration. The authors divided them into 10 groups according to the RKI, however they did not give any number of patients assigned to each group. Could you provide this data? Later in their KM analysis they stratified these patients later into two groups.

7 patients from mig-group received liver transplantation for acute liver failure. Were in this group also patients who stayed in Germany temporary and moved to their countries after transplantation?

Did you analyse also graft survival in both groups? If so did you find any differences? It would be also good to know if the compliance after liver transplantation did not differ between two groups.

From your KM analysis (patients at risks) it seems that majority of mig-group has been transplanted in the later period of your study period. Do you have any explanation for this?

I would be very careful in extrapolating the result of this study on the German situation as the authors did in their conclusions. The retrospective and single-center nature of this study is a serious limitation, so it would be very interesting a have a national data on this topic, before drawing a conclusion that migration background is not a risk factor for the outcome in liver transplantation.

General comment:

As you perform extensive analysis of your relatively small data, the manuscript is not easy to read and its message is somehow lost in the text. I would shorten this manuscript and focus on the most important issues.

Additional comment:

In my opinion inclusion of Turkey in the Eastern Europe is not correct.

**********

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 to be viewed.]

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 us at figures@plos.org. Please note that Supporting Information files do not need this step.

Liver transplantation in patients with a history of migration – a German single center comparative analysis

PONE-D-19-18755R1

Dear Dr. Bucher,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. 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 enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and 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.

With kind regards,

Frank JMF Dor, M.D., Ph.D., FEBS, FRCS

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

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

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: The authors improved their manuscript substantially according to the reviewers’ comments. I am also satisfied with their answer to my questions. I do not have any further comments.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Jacques Pirenne

Reviewer #2: No