Efficacy and safety of rifaximin in preventing hepatic encephalopathy: A systematic review and meta-analysis

Yangyang Hu; Xing Zhang; Ying Xiao; Zhinian Wu; Yadong Wang

doi:10.1371/journal.pone.0323359

Peer Review History

Original SubmissionAugust 4, 2024
4 Aug 2024 Author Response https://doi.org/10.1371/journal.pone.0323359.r001
29 Oct 2024 Decision Letter - Peter Starkel, Editor PONE-D-24-31116Efficacy and safety of Rifaximin in preventing hepatic encephalopathy: a Systematic Review and Meta-AnalysisPLOS ONE Dear Dr. Wang, 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 Dec 13 2024 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. 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(Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: In this paper, Hu and colleagues conducted a meta-analysis of the efficacy and safety of rifaximin in the prevention of hepatic encephalopathy (HE). The main problem with this paper is that the authors do not clearly define the concept of HE prevention. Is it primary or secondary prevention? This lack of definition makes the manuscript confusing and not easy to read from the abstract to the conclusion. Other important comments: -I do not understand why the authors used "fulminant hepatic failure with cerebral oedema" as a keyword? -Study selection section: the authors mentioned that the patients had CLD "mainly consisting of cirrhosis". What are the other forms of chronic liver disease? I think it should be only cirrhotic patients. The authors should clarify this. -I do not have access to Figure S1. -The authors mentioned LOLA in the introduction and study design, but there are no data on LOLA in the results. Authors should clarify. -There is no legend for the figure. Minor comments: -In the abstract: NADs is not defined. -Authors should use TIPSS and not TIPS. -In the secondary outcomes section, authors should modify “3.4.2.2 Hospitalization rate”. ****** 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 . 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Revision 1
6 Feb 2025 Author Response Dear Editor, Thank you very much for your decision letter and advice on our manuscript (PONE-D-24-31116) entitled “Efficacy and safety of Rifaximin in preventing hepatic encephalopathy: a Systematic Review and Meta-Analysis”. We also thank the reviewers for the constructive comments and suggestions. We have revised the manuscript accordingly, and all amendments are indicated by red font in the revised manuscript. In addition, our point-by-point responses to the comments are listed below this letter. We hope that our revised manuscript is now acceptable for publication in your journal and look forward to hearing from you soon. With best wishes, Yours sincerely, Yadong Wang et al. First of all, we would like to express our sincere gratitude to the reviewers for their constructive and positive comments. In the past two months, we have updated our search methods based on the suggestions and doubts of reviewers to ensure the correctness of our study. The results and descriptions have been supplemented or revised in the revised manuscript. The following is our point-to-point replies to the questions raised by reviewers, please review. Replies to Reviewer 1 Reviewer #1: In this paper, Hu and colleagues conducted a meta-analysis of the efficacy and safety of rifaximin in the prevention of hepatic encephalopathy (HE). The main problem with this paper is that the authors do not clearly define the concept of HE prevention. Is it primary or secondary prevention? This lack of definition makes the manuscript confusing and not easy to read from the abstract to the conclusion. Reply: Thank you for reviewing this article and constructive comments. I 'm sorry to misinterpret your presentation. Our meta-analysis included all articles, including primary and secondary prevention, and to avoid misunderstandings, we added the corresponding location in the revised manuscript for your review. The study showed that RFX was not superior to the control group in the primary prevention of HE. However, this meta-analysis more supports that RFX is beneficial for the secondary prevention of HE, especially in stratified analysis confirming that RFX reduces the risk of HE after TIPS. These results are also described in the ‘Discussion’ section. Given your suggestion to increase article readability and avoid logical confusion, we readjust some of the wording in the original text based on your comments. The corresponding contents are marked in ‘Revised Manuscript with Track Changes’ and please review them again. Other important comments: -I do not understand why the authors used "fulminant hepatic failure with cerebral oedema" as a keyword? -Study selection section: the authors mentioned that the patients had CLD "mainly consisting of cirrhosis". What are the other forms of chronic liver disease? I think it should be only cirrhotic patients. The authors should clarify this. -I do not have access to Figure S1. -The authors mentioned LOLA in the introduction and study design, but there are no data on LOLA in the results. Authors should clarify. -There is no legend for the figure. Reply: Thank you very much for your professional comments on our article. In view of your five questions above mentioned, the explanations are as follows: -We apologize that our negligence increases your misunderstanding, so we intend to include all HE patients initially in this study, including acute liver failure (previously called fulminant liver failure), which is also to avoid that incomplete literature search may affect the final results of meta-analysis. It was confirmed that no fulminant hepatic failure-related studies were included in the meta-analysis literature, so it was deleted in the revised manuscript. Please review here. -We sincerely thank you for your valuable feedback to improve the quality of our manuscript. As you say, HE is a syndrome of psycho-behavioral abnormalities in patients with liver failure or cirrhosis caused by different triggers. It was verified again that there were indeed two articles in the studies included in this article that the authors described CLD, but the authors did not specify the category of so-called CLD. Therefore, according to your professional suggestions, we eliminated those two literatures and re-performed Meta-analysis, so that all the subjects were patients with liver cirrhosis. We also revised the results of the latest meta-analysis of the included literature and reviewed multiple corresponding contents in the text (e.g. 'Study selection and Introduction data extraction' and so on) were modified to replace CLD with cirrhosis, please review again. -We are very sorry for not being able to access Figure S1.We scrutinized the content and order of all pictures uploaded and corrected these errors in a timely manner. Thank you again for careful review. -Because LOLA is a common medicine to prevent/treat HE in patients with liver disease. Therefore, during the literature search, randomized controlled studies using other interventions (e.g. NADs, other antibiotics, LOLA, and placebo) were included in order to compare the differences between RFX and these agents in the prevention of HE. This is also in line with the study objectives of this paper. However, no literature was found comparing RFX with LOLA by appropriately and rigorously 's search strategy. We also respect the search results. The results of subgroup analyses for the remaining interventions (e.g. NADs, other antibiotics, and placebo) are shown in Figure 2. Please review again. -We apologize for the confusion caused by figures. Figures’ notes have been added at corresponding locations. Please review again. Minor comments: -In the abstract: NADs is not defined. -Authors should use TIPSS and not TIPS. -In the secondary outcomes section, authors should modify “3.4.2.2 Hospitalization rate”. Reply: Thanks to your meticulous review. We apologize for the inconvenience caused by our negligence. -NADs means nonabsorbent disaccharides, mainly including lactulose and lactitol. Following your suggestion, we illustrate the category of NADs within ‘()’ after the first 'NADs'. This is more conducive to readers' reading and understanding. Thank you for your advice, please review again. -We searched the literature and found that there were two expressions, transjugular intrahepatic portosystemic shunt (TIPS) and transjugular intrahepatic portosystemic stent shunt (TIPSS), and TIPSS was more accurate, and we have corrected all "TIPS" in the text to "TIPSS". Please review again. -Thank you for your meticulous and patient review and apologize for my negligence, and we have revised the original text and painstakingly reviewed it again Attachments Attachment Submitted filename: Reply letter to editor.docx https://doi.org/10.1371/journal.pone.0323359.r003
8 Apr 2025 Decision Letter - Peter Starkel, Editor Efficacy and safety of Rifaximin in preventing hepatic encephalopathy: a Systematic Review and Meta-Analysis PONE-D-24-31116R1 Dear Dr. Wang, 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. If you have any questions relating to publication charges, 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 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, Peter Starkel, M.D., Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: The authors have addressed my comments. The paper has been improved and the changes and corrections made to the paper make it more sound with a message that is closer to the clinical reality. For me it is suitable for publication. https://doi.org/10.1371/journal.pone.0323359.r004
Formally Accepted
Acceptance Letter - Peter Starkel, Editor PONE-D-24-31116R1 PLOS ONE Dear Dr. Wang, 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. 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 Peter Starkel Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0323359.r005

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