PONE-D-23-02918Marijuana Use is Inverse Associated with Liver Steatosis Detected by Transient Elastography in the General United States Population in NHANES 2017-2018: A Cross-sectional StudyPLOS ONE

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Partly

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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Reviewer #1: Yes

Reviewer #2: Yes

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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: In the present manuscript the Authors report the results of a cross-sectional study investigating the association between marijuana use and liver steatosis and fibrosis detected through VCTE in the general US population using data from the recent 2017-2018 NHANES database.

The topic is certainly of interest and not frequently studied. I have the following comments:

1. Consider changing the manuscript title as follows: Marijuana use is inverseLY associated..."

2. NHANES data are from a complex survey. As per CDC guidance, appropriate sampling weights should be used in all statistical analyses.

3. I suggest adjusting the models for BMI. Please amend

Reviewer #2: The paper by Du R et al is cross-sectional analysis of NHANES round in which transient elastography was performed in the general population and indirect evidence of fatty liver content (CAP) and fibrosis (LSM) could be achieved and associated with self-reporting of marijuana use.

In spite of a lack of univariate association, when the analysis was performed adjusting for many relevant variables, the use of marijuana was associate with lower risk of liver steatosis but no association could be detected with liver fibrosis

Specific comments

1) It is my understanding that the analysis was performed without considering parameters of adiposity (BMI or waist circumference). It is well known that they are tightly related to fatty liver and to higher risk of fibrosis and in turn it is reported by the authors that the use of marijuana is associated with overweight/obesity. My advice it to test whether the independent association with use of cannabinoid remains significant adjusting for parameters of body adiposity

2) Similarly, I am wondering whether data about indirect biomarkers of insulin resistance (HOMA-IR) were considered as pathogenic modulator of the association

3) Following the same line of pathogenic reasoning I am wondering whether biomerkers of low grade inflammation are available

4) In addition, chronic kidney disease may also be associated with fatty liver and fibrosis, especially the albuminuric phenotype. These adjustments should be performed as well

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Reviewer #1: No

Reviewer #2: No

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Marijuana Use is Inversely Associated with Liver Steatosis Detected by Transient Elastography in the General United States Population in NHANES 2017-2018: A Cross-sectional Study

PONE-D-23-02918R1

Dear Dr. Yang,

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,

Saral Rajiv Desai, M.D., C.C.R.P, C.C.R.C

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

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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

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

Reviewer #1: 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

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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

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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: I congratulate the Authors for their thorough revision, which addressed all the points I previously raised. I have no further comments.

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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

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