PONE-D-22-24135Non-alcoholic Fatty Liver Disease is Not Associated with Impairment in Health-related Quality of Life in Virally Suppressed Persons with Human Immune Deficiency VirusPLOS ONE

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"Dr. Gawrieh consulting: TransMedics, Pfizer. Research grant support: Cirius, Galmed, Viking and Zydus. Dr. Corey serves on the scientific advisory board for Theratechnologies, Novo Nordisk and BMS and has received grant funding from Boehringer-Ingelheim, BMS and Novartis, Dr. Lake receives research support from Gilead Sciences and Zydus. In the past 12 months she has received research support from Pfizer, CytoDyn, and Oncoimmune, and has served as a consultant to Merck and Theratechnologies, Dr. Samala, Dr. Desai, Dr. Debroy, Ms.Sjoquist, Ms. Robison, Ms. Bhamidipalli, Dr. Saha, Dr. Zachary, Dr. Akisik, and Dr. Tann have nothing to disclose. Dr. Robbin has served as a consultant for SEED , Dr. Gupta reports consultancy/advisory fees from Gilead Sciences, Inc. and ViiV Healthcare and research support from the NIH, Indiana University School of Medicine, and ViiV HealthCare, Dr. Chung has received research grant support (to institution) from Boehringer Ingelheim, BMS, Roche, Gilead, Janssen, and GSK , Dr. Chalasani has ongoing research support from Eli Lilly, Galectin Therapeutics, Intercept, and Exact Sciences, In the past 12 months, he has received consulting fees from Abbvie, Madrigal, Nusirt, Allergan, Siemens, Genentech, Zydus, La Jolla, Axcella, Foresite Labs, and Galectin Therapeutics."

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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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

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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: This analysis assesses quality of life in NAFLD with a generic tool and compared HIV-infected and non-infected patients. The strength is the large cohort and the presence of a control group. Limitations arise from the use of a single non-liver disease and non-HIV specific tool. Overall, this is an important study and the information will guide the field. I have included comments below:

The abstract needs to be checked – in the first sentence liver “disease” is missing

The prevalence of hepatic steatosis exceeds the estimates in the general population by far! This is an interesting observation that has been captured in other cohorts, e.g. PMID: 35996039. Do the authors consider screening for NAFLD in HIV ? A section in the discussion would be welcome. The same study reported on an HIV-specific tool and observed impact of significant fibrosis on QoL – this could be added in the discussion (PMID: 35996039)

It could be mentioned that alcohol assessment (ADUIT >8) leaves room for harmful alcohol consumption if not assessed clinically.

QoL is strongly impacted by sex with women reporting lower levels of QoL in all analysis. I could not see lower OoL in this analysis (table 2) – clearly here a male dominance and transgender aspect could be the reason for this. Then again male sex was associated with higher levels in supp. Table 3. Please comment.

Please indicate when the SF-36 was completed in relation to the diagnostic test for NAFLD. At the same time? Up to 6 or 12 month ?

In the literature there have been reports of TAF impacting obesity – can you provide data on the ART backbone?

Reviewer #2: The authors describes very well Quality of life related outcomes in PLWH.

However some additional data are required:

-In table 1 must be added the antiretroviral drug classes that PLWH are taking and the duration of HIV infection

-nadir CD4 is significantly associated with HRQOL ; how many patients were affected by severe opportunistic infections during their clinical history?

-no data on therapy for diabetes are included ; it could be better to have data on the percentages of patients on therapy because these data could impact on HRQOL

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Reviewer #1: Yes: Jörn Schattenberg

Reviewer #2: No

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Non-alcoholic Fatty Liver Disease is Not Associated with Impairment in Health-related Quality of Life in Virally Suppressed Persons with Human Immune Deficiency Virus

PONE-D-22-24135R1

Dear Dr. Gawrieh,

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,

Pavel Strnad

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Thank you for giving me the opportunity to handle this interesting manuscript!

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

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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 #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

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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

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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 #1: Yes

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 #1: Nothing to add - thorough analysis - in their revision, my previous comments have been addressed.

Reviewer #2: (No Response)

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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: Jörn M. Schattenberg M.D.

Reviewer #2: No

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