Association between uric acid and non-alcoholic fatty liver disease in patients with hypertension

Yan Zhao; Zhenwei Wang; Yang Liu; Ting Yang; Zhuang Li; Ao Gao; Lei Cao; Chongyang Ma

doi:10.1371/journal.pone.0341949

Peer Review History

Original SubmissionNovember 1, 2025
11 Dec 2025 Decision Letter - Aleksandra Klisic, Editor Dear Dr. Zhao, 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. Please submit your revised manuscript by Jan 25 2026 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'. 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We look forward to receiving your revised manuscript. Kind regards, Aleksandra Klisic Academic Editor PLOS One Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. 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 https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. 3. Thank you for stating the following financial disclosure: National Health Commission of the People's Republic of China At this time, please address the following queries: a) Please clarify the sources of funding (financial or material support) for your study. List the grants or organizations that supported your study, including funding received from your institution. b) State what role the funders took in the study. If the funders had no role in your study, please state: “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.” c) If any authors received a salary from any of your funders, please state which authors and which funders. d) If you did not receive any funding for this study, please state: “The authors received no specific funding for this work.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 4. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section. 5. In the online submission form, you indicated that the data are available upon reasonable request. Extra data can be accessed via the Dryad data repository at http://datadryad.org/with the doi:10.5061/dryad.7d7wm3809. All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either a. In a public repository, b. Within the manuscript itself, or c. Uploaded as supplementary information. This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval. 6. 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. 7. 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. [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? 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 Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: Yes ****** Reviewer #1: The paper is mostly well composed, organized logically, and simple to understand. The research question is well articulated, and the reasoning for investigating uric acid as a possible risk factor for NAFLD in this group is strongly supported. The results align with current literature and provide further perspective on a particular clinical subgroup that is rarely explored in depth. this is a thoughtfully structured and meticulously executed research. The findings are reliable, the examination is fitting, and the document is well organized. It satisfies PLOS ONE's criteria for methodological rigor, ethical clarity, and reporting transparency. I suggest small changes before approval. Particularly: Modify the data availability statement to align with the requirements of PLOS ONE. Include a brief comment on model diagnostics and discuss the minimal practical improvement in AUC. Fix small typographical and formatting errors. After these minor adjustments, the manuscript will be prepared for publication and will significantly enhance the literature regarding metabolic risk factors among hypertensive groups Reviewer #2: This is a very interesting study. It was also thoroughly done. The data was well tabulated and also well interpreted. I enjoyed reading every part of this research article. Well done. Just one thing to point out; the last sentence of the penultimate paragraph in the discussion section doesn't have a correlating reference. It therefore should be rephrased to prevent flagging it for plagiarism and the corresponding reference should be included. Thank you. ****** 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: Malak M Abdulqadir (Alagoury) Reviewer #2: Yes: Dr. Temiloluwa Adefusi ******** [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 ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation. NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications. https://doi.org/10.1371/journal.pone.0341949.r001
Revision 1
5 Jan 2026 Author Response Dear Dr. Klisic and Reviewers, Thank you for the opportunity to revise our manuscript (PONE-D-25-57606) entitled “Association between uric acid and non-alcoholic fatty liver disease in patients with hypertension” for consideration in PLOS ONE. We sincerely appreciate the editors and reviewers for their time, insightful comments, and constructive suggestions, which have significantly strengthened our manuscript. We have carefully addressed all the points raised, and the corresponding changes have been incorporated into the revised manuscript. A point-by-point response is provided below. Response to Journal Requirements: 1. Style Requirements: We have carefully reviewed and formatted our manuscript to fully comply with PLOS ONE’s style requirements, including the use of the provided templates for the main body and title/authors/affiliations sections. 2. & 3. Funding Information and Financial Disclosure: We apologize for the initial discrepancy. The correct and complete funding statement is as follows: This research was sponsored by the National Key Research and Development Program of China (No. 2024YFC3506301), and Wang Qi's National Master of Traditional Chinese Medicine Inheritance Studio (DFRCYJ-2024A-001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This statement has been updated in the manuscript file. The authors received no specific funding for this work. And no author received a salary from these funders for conducting this study. 4. Ethics Statement: The ethics statement has been reviewed and now appears only in the Methods section of the manuscript. Any duplicate statements in other sections have been removed. 5. Data Availability: The Data Availability Statement in the manuscript has been updated as below to clearly reflect this public deposition, ensuring full compliance with PLOS ONE’s data policy. The data that support the findings of this study are publicly available from the Dryad repository. These data can be accessed directly, without any special permissions, via the official repository: https://doi.org/10.5061/dryad.7d7wm3809. 6. & 7. References: We have reviewed the reviewers' comments and confirm that no specific recommendations to cite previously published works were made. We have thoroughly reviewed our reference list, ensuring it is complete, correct, and contains no retracted papers. Response to Reviewer Comments: Reviewer #1: We thank the reviewer for the positive assessment and valuable suggestions. 1) Data Availability Statement: We have revised the Data Availability Statement in the manuscript to explicitly state: “The data that support the findings of this study are publicly available from the Dryad repository. These data can be accessed directly, without any special permissions, via the official repository: https://doi.org/10.5061/dryad.7d7wm3809.” This aligns with PLOS ONE’s requirements. 2) Include a brief comment on model diagnostics and discuss the minimal practical improvement in AUC: We sincerely thank the reviewer for this crucial suggestion. We have now added a comprehensive new subsection (3.5 Robustness analysis and model diagnostics) in the Results. This section details: Model Diagnostics and Robustness: We have conducted a comprehensive diagnostic evaluation of the final logistic regression model to ensure the robustness and reliability of the results, which includes the following: (1) Core Parameter Stability (Bootstrap Resampling Validation): To directly quantify the uncertainty of model parameters under sampling variability, we employed the Bootstrap method (1,000 replicates) to calculate robust standard errors and confidence intervals. The results show that the independent positive association between the key variable uric acid (UA) and NAFLD is highly stable (B = 0.002, Bootstrap 95% CI: 0.000 – 0.004, P = 0.019). This interval excludes zero and is precise, serving as the core evidence for the robustness of our conclusion. (2) Model Goodness-of-Fit: The Hosmer-Lemeshow test indicated that the full model incorporating UA demonstrated good fit (χ² = 11.668, P = 0.167). Multicollinearity: The variance inflation factor (VIF) for all independent variables was below 10, with the VIF for the key variable UA being 1.248. This indicates the absence of severe multicollinearity, allowing for a clear estimation of the independent effects of UA. Outliers and Influential Points: A sensitivity analysis was performed after identifying and excluding 55 potential outliers. The direction, magnitude, and statistical significance of the association between UA and NAFLD remained unchanged (OR = 1.003, 95% CI: 1.001–1.005, P = 0.014). This confirms that our primary finding is not driven by a small number of extreme data points and possesses generalizability. (3) Conclusion: The aforementioned analyses form a complete chain of evidence. Bootstrap validation confirms the stability of the statistical inference, the H-L test and collinearity diagnostics ensure the rationality of the model construction, and the sensitivity analysis rules out the excessive influence of outliers. Together, they collectively support the high robustness of the study's conclusions. In the Discussion, we have integrated a dedicated comment (in the first paragraph) addressing the minimal practical improvement in AUC. We acknowledge the modest absolute increase (from 0.770 to 0.772) and discuss its practical value in the context of UA being a routine, low-cost test in hypertension management, thus offering a cost-effective enhancement to risk stratification. 3) Typographical and Formatting Errors: We have meticulously proofread the entire manuscript and corrected the typographical and formatting errors. Reviewer #2: We thank the reviewer for their encouraging feedback and for identifying the oversight. Reference in the Discussion: We have rephrased the final sentence of the penultimate paragraph in the Discussion section and have included the appropriate citation ([36]) to support the statement regarding future research directions for elucidating pathophysiological mechanisms. This corrects the previous omission and ensures proper attribution. Conclusion We believe that all concerns raised have been adequately addressed. The revisions have substantially strengthened the clarity and coherence of the presentation, as well as the overall rigor of the scientific argument. We have uploaded the following files via the submission system: 1. Response to Reviewers (this letter). 2. Revised Manuscript with Track Changes (highlighting all modifications). 3. Manuscript (clean version without tracked changes). Thank you again for your consideration. We look forward to your decision on our revised manuscript. Sincerely, Attachments Attachment Submitted filename: response to reviewers.docx https://doi.org/10.1371/journal.pone.0341949.r002
15 Jan 2026 Decision Letter - Aleksandra Klisic, Editor Association between uric acid and non-alcoholic fatty liver disease in patients with hypertension PONE-D-25-57606R1 Dear Dr. Zhao, 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. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support . If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- 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. Kind regards, Aleksandra Klisic Academic Editor PLOS One Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions??> Reviewer #2: Yes ****** 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 Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #2: Yes ****** Reviewer #2: All comments have been addressed, the article is more concise and easier to read and plagiarisms have been sorted. Well done ****** 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: Yes: ADEFUSI TEMILOLUWA ******** https://doi.org/10.1371/journal.pone.0341949.r003
Formally Accepted
Acceptance Letter - Aleksandra Klisic, Editor PONE-D-25-57606R1 PLOS One Dear Dr. Zhao, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS One. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Aleksandra Klisic Academic Editor PLOS One https://doi.org/10.1371/journal.pone.0341949.r004

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