Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript addresses an important clinical topic and provides valuable biopsy-based histopathological data in children with short bowel syndrome and IFALD managed within an intestinal rehabilitation program. The integration of histopathology with nutritional and clinical outcomes represents a relevant strength.

However, several major issues should be addressed before publication.

First, the manuscript is substantially affected by selection bias, as only 16 of 72 eligible patients underwent liver biopsy. The indications for biopsy should be clarified in detail, and a patient flow diagram is strongly recommended.

Second, the statistical analysis section does not correspond to the reported results. Logistic regression is described but regression outputs (ORs, confidence intervals, p-values) are not presented. Given the limited sample size, the authors should either remove regression analyses or provide complete results and justify model feasibility.

Third, the definitions of active and chronic IFALD require clarification and supporting references, or should be presented explicitly as study-specific operational definitions.

Fourth, conclusions should be moderated. Statements suggesting that histopathological abnormalities precede biochemical changes imply temporal causality that cannot be demonstrated with the current retrospective design.

Additional improvements include:

• clearer reporting of PN composition and lipid exposure;
• definition of enteral autonomy;
• inclusion of statistical comparisons in Table 4;
• correction of editorial inconsistencies and table formatting;
• discussion of biopsy limitations and feasibility.

Overall, the manuscript has potential but requires substantial revision to improve methodological transparency and align conclusions with the presented data.

Author Response

Please find the attachment below.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The study titled "Biopsy-Proven Intestinal Failure–Associated Liver Disease in Pediatric Short Bowel Syndrome: Histopathological Findings and Clinical Outcomes" aims to establish a correlation between histopathological findings and intestinal failure in pediatric patients using PN (prophylaxis).

The study uses tissue and blood samples collected almost 10 years ago. It is unclear how and where these tissues and blood were stored, nor under what conditions.

The results are very superficial, with simple demographic data and a very small sample size. The biochemical parameters are basic, lacking inflammatory markers that would allow for an assessment of the patients' condition.

The histopathological results, which are the focus of the study, are very simple, just a poor-quality image without quantification or even lesion scores. The discussion is not in-depth, and there is no clinical justification for the correlation. In this sense, the study is very weak, making it difficult to apply.

 

Author Response

Dear Editor,

We thank you and the reviewers for their insightful reviews of our manuscript. We greatly appreciate the reviewers; thoughtful and helpful comments/suggestions and your editorial assistance. We have addressed these comments, added the highlights, and made the appropriate changes as follows:

REVİEWER 2

1. The study uses tissue and blood samples collected almost 10 years ago. It is unclear how and where these tissues and blood were stored, nor under what conditions.

 

• Thank you for this suggestions; we added this paragrapf in material methods seciton.

 

Our study includes patients with short bowel syndrome who underwent liver biopsy between 2015 and 2022.

Samples from patients who had liver biopsies during surgery are reported in approximately one week. We retrospectively collected those reports and blood test results.

 

2. The results are very superficial, with simple demographic data and a very small sample size. The biochemical parameters are basic, lacking inflammatory markers that would allow for an assessment of the patients' condition.

 

• Thank you for this comment but we did not include biochemical inflammatory parameters such as CRP and sedimentation rate in the data because they are not specific or guiding in IFALD.

 

3. The histopathological results, which are the focus of the study, are very simple, just a poor-quality image without quantification or even lesion scores. The discussion is not in-depth, and there is no clinical justification for the correlation ??

• Thank you for your suggestion and we added table 5 for correlation of IFALD and mortality or enteral autonomy

 

 

 

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

I have carefully reviewed the authors’ responses and the revised version of the manuscript. I appreciate the substantial effort made to address the reviewers’ comments. The authors have clarified the patient selection process, provided additional methodological details, expanded the statistical reporting, clarified the definitions of active and chronic IFALD, moderated the conclusions, and included the requested information regarding parenteral nutrition exposure and enteral autonomy.

Overall, the revisions have significantly improved the clarity and scientific rigor of the manuscript. While some limitations inherent to the retrospective design and the relatively small biopsy cohort remain, these issues are now adequately acknowledged and discussed by the authors.

In my opinion, the authors have satisfactorily addressed the concerns raised during the review process, and the manuscript is now suitable for publication in its current form.

Author Response

Thank you, best regards

Reviewer 2 Report

Comments and Suggestions for Authors

Dear authors,

Thank you for your response. The text is better, but still requires further adjustments.

Histopathological images should show the scale and clearly indicate the differences in the figure using arrows.

Future perspectives for the field of study should be presented based on the study data. Alternatives and their clinical applicability should be noted.

The discussion should be deepened with clinical studies and hypotheses, rather than just descriptions of studies.

Author Response

Histopathological images should show the scale and clearly indicate the differences in the figure using arrows

Response 1: Thank you for your comment and we added new histopathological image and try to indicate clearly.

Future perspectives for the field of study should be presented based on the study data. Alternatives and their clinical applicability should be noted.

The discussion should be deepened with clinical studies and hypotheses, rather than just descriptions of studies.

Response 2 : Thank you for your suggestion, and we added some future pesrpective and deepened the discussion with alternatives and their applicability . Best regards 

 

Round 3

Reviewer 2 Report

Comments and Suggestions for Authors

Dear authors,

Thank you for your response. However, there are still points to adjust in the image results. Images "E" and "F" have been manipulated and exhibit a different colouration from the others. In image studies, the same background pattern as the controls should always be used to avoid bias. Please review the images.

 

Author Response

Comments 1: However, there are still points to adjust in the image results. Images "E" and "F" have been manipulated and exhibit a different colouration from the others. In image studies, the same background pattern as the controls should always be used to avoid bias. Please review the images.

Response 1: Thank you for your comment editor.

Dear Editor,
As we stated in the figure legend, different histochemical stains were used in figures E and F. Hematoxylin-eosin stain was used in figures A-D, while Masson trichrome stain was used in figures E and F, and this stain is routinely used in liver biopsies to demonstrate liver fibrosis. This different stain is commercially available and is a widely used additional examination in pathology routine.
 Best regards