The bilirubin-to-albumin ratio as a potential prognostic biomarker for all-cause mortality in patients with acute decompensated cirrhosis: A prospective study

Hien Viet Quang Nguyen; Thang Viet Luong; Trung Nguyen Tran; Hai Nguyen Ngoc Dang

doi:10.1371/journal.pone.0337206

Peer Review History

Original SubmissionMay 28, 2025
10 Jul 2025 Decision Letter - Hans L. Tillmann, Editor Dear Dr. Nguyen Ngoc Dang, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it may have some merit but does not currently 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. AUC curves for MELD, MELD-Na and MELD 3.0 and Child-Pugh should be presented, as it seem that MELD 3.0 is almost superior to Bilirubin/Albumin, albeit your study was too small to identify a significant difference. Without a power calculation to demonstrate that sample size was large enough to discriminate a difference in performance you cannot claim equivalence. Explore if etiology of disease matter for survival Patient likely need to divide in ACLF and non-ACLF, and explore at least in an explorative analysis. For patients with ACLF the Clif score should be given. publication criteria and not, for example, on novelty or perceived impact. For Lab, Study and Registered Report Protocols: These article types are not expected to include results but may include pilot data. ============================== Please submit your revised manuscript by Aug 24 2025 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'. A marked-up copy of your manuscript that highlights changes made to the original version. 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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. Additional Editor Comments (if provided): [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: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes ****** Reviewer #1: 1. Please give a proper rationale how B/A ratio will add to the already established prognostic scores. 2. Please explain whether it is superior/inferior to the existing scores. 3. Please revise the discussion and expand, adding the similar studies and comparing it with yours. ****** 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 ******** [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". 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Revision 1
7 Aug 2025 Author Response REBUTTAL LETTER Dear Editor and Reviewers, We would like to express our sincere gratitude to the reviewers and the editor for their thorough review and insightful comments on our manuscript. Your valuable feedback has significantly helped us improve the quality and clarity of our work. We greatly appreciate your time and effort in providing constructive suggestions, and we are committed to addressing all the points raised to ensure that our manuscript meets the highest standards. We would now like to respond to the specific comments and suggestions provided by the reviewers as follows: RESPONSE TO EDITOR: #1: AUC curves for MELD, MELD-Na and MELD 3.0 and Child-Pugh should be presented, as it seem that MELD 3.0 is almost superior to Bilirubin/Albumin, albeit your study was too small to identify a significant difference. Without a power calculation to demonstrate that sample size was large enough to discriminate a difference in performance you cannot claim equivalence. Response: We have addressed this point by including additional data in Supplementary Table 2, where the AUC values of the MELD, MELD-Na, MELD 3.0, and Child-Pugh scores for predicting 30-day, 90-day, and 180-day mortality are presented alongside the B/A ratio. Initially, the MELD-based models and Child-Pugh score exhibited slightly higher AUCs than the B/A ratio at the 30-day mortality endpoint. However, this advantage diminished over time, and the predictive performance of the B/A ratio became comparable at later timepoints. Although our study sample is comparable to those of previous research in this field, we acknowledge that it may still be underpowered to detect statistically significant differences in discrimination performance across models. As you correctly pointed out, the absence of a formal power calculation limits our ability to claim equivalence between the B/A ratio and established prognostic scores. We have now clarified this limitation explicitly in the Discussion section. Thank you again for highlighting this important consideration. #2: Explore if etiology of disease matter for survival Response: We are thankful for your valuable recommendation. In our Cox regression Model II, we have already adjusted for etiologies and precipitating factors, including key contributors to acute decompensation, as part of the fully adjusted model. To enhance clarity, we will elaborate on this aspect more explicitly in the Results section to ensure that readers fully understand the scope of adjustment. We believe that conducting a separate analysis focusing solely on etiology-specific survival would be beyond the scope of our current study objectives and could potentially divert from the primary aim, which is to evaluate the prognostic utility of the B/A ratio in acute decompensation. Nevertheless, we appreciate your suggestion and consider it a valuable direction for future research. #3: Patient likely need to divide in ACLF and non-ACLF, and explore at least in an explorative analysis. Response: We are thankful for your valuable recommendation. Initially, we did perform subgroup division between ACLF and non-ACLF patients (AD) and conducted comparative analyses. However, we initially decided not to include these data in detail to maintain a concise manuscript and avoid overburdening the reader with excessive content. In light of your valuable suggestion, we have now reinstated these analyses in the Baseline Clinical Characteristics section and provided the detailed data in Supplementary Table 1. This approach ensures that readers who are specifically interested in the differences between ACLF and non-ACLF patients can access the relevant information, while preserving the overall clarity and focus of the main text. Thank you again for your helpful recommendation. #4: For patients with ACLF the Clif score should be given. Response: We are thankful for your valuable recommendation. In response to your recommendation, we have included detailed information on relevant prognostic scores specifically for patients with ACLF, including CLIF-C ACLF, CLIF-SOFA, CLIF-C OF, Child-Pugh, MELD, MELD-Na, and MELD 3.0 in Supplementary Table 1. These additions provide a more comprehensive overview of disease severity and support further interpretation of outcomes in this subgroup. Thank you for highlighting this important point. RESPONSE TO REVIEWER: #1: Please give a proper rationale how B/A ratio will add to the already established prognostic scores. Response: We are thankful for your recommendation. Trong nghiên cứu của chúng tôi It is unsurprising that the bilirubin-to-albumin (B/A) ratio initially appeared independently associated with outcome after partial adjustment, yet lost statistical independence once all covariates were incorporated. Acute, critically ill populations are influenced by myriad interacting factors, and in real-world practice clinicians never rely on a single parameter to judge prognosis. This rationale underpins the development of multi-component scores such as MELD, MELD-Na and MELD 3.0, which integrate several laboratory variables. The value of the B/A ratio lies in its simplicity: it offers a rapid, holistic snapshot while more complex calculations and additional tests are still pending. Our aim was therefore not to create a solitary marker that supplants existing tools, but to highlight a readily available index whose performance approaches that of more elaborate scores. Clinical decision-making is analogous to diagnosis: no physician bases a diagnosis on one symptom or one test result. A meticulous examination is required, synthesising multiple clinical signs and investigations before reaching a final judgment. Likewise, we do not advocate replacing established clinical or laboratory assessments with the B/A ratio; rather, we propose it as a quick, initial risk-stratification aid in acute decompensated cirrhosis, prompting timely, decisive management while comprehensive scores are being calculated. Accordingly, we deliberately use the qualifier “potential prognostic” in the title, and we now emphasise in the Discussion that the B/A ratio is intended to complement—not replace—other critical clinical and paraclinical information. #2: Please explain whether it is superior/inferior to the existing scores. Response: As previously mentioned, our study did not aim to demonstrate the superiority of the B/A ratio over established prognostic models. We fully acknowledge that such a comparison would be inappropriate, as multi-component scores like MELD, MELD-Na, and MELD 3.0 incorporate a broader range of laboratory parameters and clinical information, which naturally enhances their prognostic accuracy. Instead, our objective was to highlight the practical value of the B/A ratio—its simplicity, accessibility, and ease of use—as a rapid, integrative marker that can provide early prognostic insight while awaiting more comprehensive test results. While the B/A ratio may not outperform these established models, its comparable performance and clinical convenience make it a valuable adjunctive tool, particularly in resource-limited settings or when rapid decision-making is essential. #3: Please revise the discussion and expand, adding the similar studies and comparing it with yours. Response: Initially, we intended to include comparisons with similar studies; however, the majority of existing literature on the bilirubin-to-albumin (B/A) ratio focuses on neonatal or pediatric populations. Due to fundamental physiological and clinical differences between children and adults, especially in liver disease progression and systemic responses, we believe that direct comparisons across age groups would be inappropriate and potentially misleading. Therefore, rather than drawing comparisons with these pediatric-focused studies, we opted to emphasize the pathophysiological rationale behind the prognostic value of the B/A ratio in adults with acute decompensation. This approach, in our view, aligns more closely with the aims of our research and provides a more relevant context for interpreting our findings. Nonetheless, we fully agree that comparative discussion with future adult-focused studies will be essential as more evidence emerges. In addition to the revisions outlined above, we have diligently addressed all reviewer and editor comments. We’ve also conducted a thorough review of the manuscript for grammatical precision, scientific terminology, reference accuracy, and unit consistency, adhering to journal guidelines. These efforts have significantly elevated the manuscript’s quality and clarity. We eagerly await your feedback on this revised version. Thank you once again for your invaluable contributions. Sincerely, The Authors Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0337206.r002
22 Aug 2025 Decision Letter - Hans L. Tillmann, Editor Dear Dr. Nguyen Ngoc Dang, 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. As you may not be familiar with prior scores related to Albumin and Bilirubin, different from MELD I now listed those score below for the authors for easy incorporation; I also including the references are listed below. There are previous scores using Albumin and Bilirubin one including Platelets assessing the “liver reserve”. While this is in the setting of HCC resection, especially ACLF is where liver reserve plays a role, and thus should be included in assessment. <table border="0" cellpadding="0"> <thead> <tr> <th> Noninvasive Liver Reserve Models </th> <th> Formula </th> </tr> </thead> <tbody> <tr> <td> BiLE Score[1] 6.9 threshold </td> <td> Bilirubin (μmol/L)/100 + lactate (mmol/L) + 4 (in case of indeterminate ALF, Budd-Chiari syndrome, or phenprocoumon toxicity) -2 (in case of acetaminophen toxicity) +0 (in case of any other ALF etiology </td> </tr> <tr> <td> ALBI grade[2] 1/2/3 (≤−2.6/>−2.6 and ≤−1.39/>−1.39) </td> <td> (log₁₀ (Bilirubin (μmol/L)) × 0.66) + (Albumin (g/L) × (−0.085)) </td> </tr> <tr> <td> EZ-ALBI grade[3] 1/2/3 (≤−34.4, >−34.4 and ≤−22.2, >−22.2) </td> <td> Bilirubin (mg/dL) − (9 × Albumin (g/dL)) </td> </tr> <tr> <td> PALBI grade[4] 1/2/3 (≤−2.53), score > −2.53 and ≤−2.09)/(score > −2.09) </td> <td> 2.02 × log₁₀ Bilirubin (μmol/L) level − 0.37 × (log₁₀ Bilirubin level)² − 0.04 × Albumin level − 3.48 × log₁₀ Platelet count (1000/μL) + 1.01 × (log₁₀ Platelet count)² </td> </tr> <tr> <td> PAL grade 1/2/3 (score ≤ −3.77, score > −3.77 and ≤−3.04, score > −3.04 </td> <td> 0.777 × Albumin (g/dL) − 0.575 × (log₁₀ Platelet count) (10⁴ /μL) </td> </tr> </tbody></table> It would be important to demonstrate that a new score is either substantially simpler or substantially more accurate in predicting mortality. Of the above models, you can potentially skip the 1^st one, as it does not include Albumin, but the others would need to be explore in comparison to the new score. While the study may be too small, a power calculation, to indicate an ideal study size would still be required. ********** [1] Hadem J, Stiefel P, Bahr MJ, Tillmann HL, Rifai K, Klempnauer J, Wedemeyer H, Manns MP, Schneider AS. Prognostic implications of lactate, bilirubin, and etiology in German patients with acute liver failure. Clin Gastroenterol Hepatol. 2008 Mar;6(3):339-45. doi: 10.1016/j.cgh.2007.12.039. PMID: 18328438 [2] Johnson PJ, Berhane S, Kagebayashi C, Satomura S, Teng M, Reeves HL, O'Beirne J, Fox R, Skowronska A, Palmer D, Yeo W, Mo F, Lai P, Iñarrairaegui M, Chan SL, Sangro B, Miksad R, Tada T, Kumada T, Toyoda H. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol. 2015 Feb 20;33(6):550-8. doi: 10.1200/JCO.2014.57.9151. Epub 2014 Dec 15. PMID: 25512453; PMCID: PMC4322258. [3] Kariyama K, Nouso K, Hiraoka A, Wakuta A, Oonishi A, Kuzuya T, Toyoda H, Tada T, Tsuji K, Itobayashi E, Ishikawa T, Takaguchi K, Tsutsui A, Shimada N, Kudo M, Kumada T. EZ-ALBI Score for Predicting Hepatocellular Carcinoma Prognosis. Liver Cancer. 2020 Dec;9(6):734-743. doi: 10.1159/000508971. Epub 2020 Oct 23. PMID: 33442542; PMCID: PMC7768152. [4]Roayaie S, Jibara G, Berhane S, Tabrizian P, Park JW, Jijin Yang J, Yan L, Guohong Han G, Izzo F, Chen M, Blanc JF, Kudo M, Roberts LR. Sherman M, Johnson P. PALBI-An Objective Score Based on Platelets, Albumin & Bilirubin Stratifies HCC Patients Undergoing Resection &Ablation Better than Child’s Classification. Poster Sessions. Hepatology. 2015;62 Suppl 1:631A 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'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols . We look forward to receiving your revised manuscript. Kind regards, Hans L. Tillmann Academic Editor PLOS ONE Journal Requirements: 1. 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. [Note: HTML markup is below. Please do not edit.] [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.] 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 PLOS at figures@plos.org . Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0337206.r003
Revision 2
15 Sep 2025 Author Response RESPONSE LETTER Dear Editor and Reviewers, We greatly appreciate your time and effort in providing constructive suggestions, and we are committed to addressing all the points raised to ensure that our manuscript meets the highest standards. We would now like to respond to the specific comments and suggestions provided by the reviewers as follows: RESPONSE TO EDITOR AND REVIEWER: #1: There are previous scores using Albumin and Bilirubin one including Platelets assessing the “liver reserve” such as ALBI, EZALBI, PALBI. While this is in the setting of HCC resection, especially ACLF is where liver reserve plays a role, and thus should be included in assessment. It would be important to demonstrate that a new score is either substantially simpler or substantially more accurate in predicting mortality. Of the above models, you can potentially skip the 1st one, as it does not include Albumin, but the others would need to be explore in comparison to the new score. Response: We sincerely appreciate this insightful comment. In response, we have incorporated the suggested scores (ALBI, EZ-ALBI, and PALBI) into our analysis, as presented in Supplementary Table 3. The results show that the B/A ratio did not differ significantly from these established models in terms of predictive performance. This further supports the notion that the B/A ratio, despite its simplicity, achieves comparable prognostic accuracy to more complex scoring systems. #2: While the study may be too small, a power calculation, to indicate an ideal study size would still be required. Response: In accordance with the suggestion, we have added a power calculation to the Methods section to indicate the ideal study size. Thank you once again for your invaluable contributions. Sincerely, The Authors Attachments Attachment Submitted filename: Response_to_Reviewers_auresp_2.docx https://doi.org/10.1371/journal.pone.0337206.r004
8 Oct 2025 Decision Letter - Hans L. Tillmann, Editor Dear Dr. Nguyen Ngoc Dang, 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 Nov 22 2025 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'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols . We look forward to receiving your revised manuscript. Kind regards, Hans L. Tillmann Academic Editor PLOS ONE Journal Requirements: 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. [Note: HTML markup is below. Please do not edit.] [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.] 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 PLOS at figures@plos.org . Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0337206.r005
Revision 3
26 Oct 2025 Author Response RESPONSE LETTER Dear Editor, We greatly appreciate your time and effort in providing constructive suggestions, and we are committed to addressing all the points raised to ensure that our manuscript meets the journal’s standards. We respond to each of your comments as follows: RESPONSE TO EDITOR: #1: When exploring the role to Albumin to Bilirubin, you need to cite in the introduction the previously and more established model, do NOT Push them into a supplement. The key question for you paper is if your new score is relevantly differnt from established scores that were already subsequently externally validated. Response: Thank you for this valuable suggestion. We have revised the introduction section to include citations of established models and previous. In addition, we have refined the introduction section to clearly define the aim of our study, explicitly stating that it compares this ratio with previously validated scoring systems. #2: You score does not need to be superior to previous score to make you paper acceptable, but it should be more clarly demonstarted how you score compared to other scores performs. Response: We appreciate your clarification. Accordingly, we have expanded the discussion section to provide a clearer comparison between the bilirubin-to-albumin ratio and existing prognostic models. #3: Please also better explain what your saple size calculation is based on. I believe your study did not aim to assess prevalence of cirrhosis, but prediction of mortality related to bilirubin to albumin ratio. Response: Thank you for this insightful comment. We have revised the method section to explain our sample size calculation. As there were no prior studies directly evaluating this ratio in our target population, we referenced recent related studies to establish a reasonable estimate for sample size determination. Once again, we are deeply grateful for your constructive feedback and the opportunity to further refine our manuscript. Your comments have greatly contributed to strengthening the scientific rigor and presentation of our work. We sincerely hope that the revisions meet your expectations. With our best regards, The Authors Attachments Attachment Submitted filename: Response_to_Reviewers_auresp_3.docx https://doi.org/10.1371/journal.pone.0337206.r006
29 Oct 2025 Decision Letter - Hans L. Tillmann, Editor Dear Dr. Nguyen Ngoc Dang, 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 2025 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'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols . We look forward to receiving your revised manuscript. Kind regards, Hans L. Tillmann Academic Editor PLOS ONE Journal Requirements: 1. 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. 2. 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. Additional Editor Comments : You getting there. The revision, did not show well how your new model compares the the established models, this would be crucial and needs to be in the main manuscript, please demonstrate how your model performs to established models, thus your supplemental table 2 & 3 needs to be part of the man manuscript, you should also include the information from supplemental table 2 & 3 into the abstract. For table 2 you may also want to show the p-value comparing your A/B score to MELD etc, as in supplemental table 3. You may also want to point out, that you show that you demonstrate that ALBI score was not significantly better than your more simple score, that can be calculated by hand vs. ALBI score, most of us would need a calculator. Though you would admit that the EZ-ALBI score can be hand calculated. But you can point out also, that while it was developed for HCC, you show that is also works for de-compensated cirrhosis independent of HCC. [Note: HTML markup is below. Please do not edit.] [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.0337206.r007
Revision 4
2 Nov 2025 Author Response RESPONSE LETTER Dear Editor, We greatly appreciate your time and effort in providing constructive suggestions, and we are committed to addressing all the points raised to ensure that our manuscript meets the journal’s standards. We respond to each of your comments as follows: RESPONSE TO EDITOR: #1: Your supplemental table 2 & 3 needs to be part of the man manuscript, you should also include the information from supplemental table 2 & 3 into the abstract. For table 2 you may also want to show the p-value comparing your A/B score to MELD etc, as in supplemental table 3. Response: Thank you very much for your comment. Initially, we were concerned that including too many tables and figures in the main text might increase the total page count. However, following your suggestion, we have incorporated the data from Supplemental Tables 2 and 3 into Table 3 of the main manuscript. In addition, the comparative AUC values between our index and established prognostic models have been added to Figure 6 for clearer visual presentation. We also updated the Abstract to include relevant information from these tables, while ensuring that the word limit requirements were not exceeded. #2: You may also want to point out, that you show that you demonstrate that ALBI score was not significantly better than your more simple score, that can be calculated by hand vs. ALBI score, most of us would need a calculator. Though you would admit that the EZ-ALBI score can be hand calculated. But you can point out also, that while it was developed for HCC, you show that is also works for de-compensated cirrhosis independent of HCC. Response: Thank you very much for your comment. We have revised the Discussion section, specifically the part on clinical implications, to emphasize that previously developed indices can also be applied in this context based on the data from our study. JOURNAL REQUIREMENTS: 1. 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. 2. 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. Response: We have carefully reviewed the references suggested by the reviewers and editors, and only cited those that are directly relevant to our study. Unrelated references were not included. In addition, we thoroughly rechecked our reference list to ensure accuracy and to confirm that none of the cited papers have been retracted. No retracted publications are cited in our revised manuscript. Once again, we are deeply grateful for your constructive feedback and the opportunity to further refine our manuscript. Your comments have greatly contributed to strengthening the scientific rigor and presentation of our work. We sincerely hope that the revisions meet your expectations. With our best regards, The Authors Attachments Attachment Submitted filename: Response_to_Reviewers_auresp_4.docx https://doi.org/10.1371/journal.pone.0337206.r008
6 Nov 2025 Decision Letter - Hans L. Tillmann, Editor The bilirubin-to-albumin ratio as a potential prognostic biomarker for all-cause mortality in patients with acute decompensation of cirrhosis: A prospective study PONE-D-25-26872R4 Dear Dr. Nguyen Ngoc Dang, 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, Hans L. Tillmann Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0337206.r009
Formally Accepted
Acceptance Letter - Hans L. Tillmann, Editor PONE-D-25-26872R4 PLOS One Dear Dr. Nguyen Ngoc Dang, 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. Hans L. Tillmann Academic Editor PLOS One https://doi.org/10.1371/journal.pone.0337206.r010

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