Title: Strain Elastography for Detecting Advanced Fontan-Associated Liver Disease: A
Retrospective Study
Version: 1 Date: 23 Mar 2025
Reviewer:  Amira A. A. Othman
Reviewer's report:
First of all
I want to congratulate the authors on their work. In this study, Imoto et al. aimed to evaluate the
effectiveness of non-invasive tests (NITs), particularly strain elastography (SE), in identifying
advanced Fontan-associated liver disease (a FALD). It compares SE’s diagnostic accuracy with
established fibrosis markers, platelet counts, and other elastography techniques. By analyzing
data from Fontan patients at Kyushu University Hospital, the study aims to determine whether
SE-derived liver fibrosis index (LFI) improves the detection of a FALD, which is crucial for
risk stratification and clinical management.
The authors handled the reviewer comments satisfactorily, nevertheless, there is an observation
for which sufficient justification must be obtained.
In general:
1. The language is generally clear, but some minor grammatical errors and awkward phrasings
could be improved. Consider having the manuscript proofread by a native English speaker or
a professional editing service.
2. Abbreviations must be fully written at their first appearance.
In Title:
1. The title is somewhat long and could be more direct. , I suggest “ Strain Elastography for
Detecting Advanced Fontan-Associated Liver Disease: a retrospective study”.
In Abstract section
2. The background subsection in the abstract :
-  Should be the shortest part of the abstract. It should briefly outline the following information:
What is already known about the subject, related to the paper in question. What is not known
about the subject and hence what the study intended to examine (or what the paper seeks to
present)? Avoid redundancy:
- The NITs vs. SE comparison is repeated multiple times
-  What does SE’s accuracy mean for patient management and follow-up?.
- Add a brief statement on how SE can impact clinical decisions.
3. In the method subsection in the abstract :
- Nothing was mentioned about the participant's age, sex, ethnicity, etc.
- It would help if you described the aim of your statistical analysis.
4. In the results subsection in the abstract :
-   Improve numerical clarity and conciseness
5. In the conclusion subsection in the abstract :
- Emphasize the clinical significance of your study: "What does SE’s accuracy mean for patient
management and follow-up?”
In the Introduction section:
6. Avoid excessive background on the Fontan procedure: The discussion on systemic venous
return and cardiac physiology could be shortened.
7. The transition from elastography techniques to SE’s potential advantages should be smoother.
8. Clarify the research gap; prior studies have assessed other elastography methods (MRE, SWE,
TE)—why focus specifically on SE?
In the Methods section:
9. Please provide the participants' sociodemographic data well.
10. How the sample size was calculated. Was a power calculation performed?
11. Explain the choice of cut-off values; how were the LFI and platelet count thresholds
determined?
12. Did patients have other liver conditions (e.g., metabolic or viral liver diseases)?
13. How did medications, age, or Fontan circulation duration impact fibrosis assessment?
In the Results section:
14. In all tables, please explain the abbreviations under tables.
15. You can title the statistical test column as “Test of significance” and use U= for the Mann–
Whitney U test, T= for the T-test, and #2 = for the Chi-square test, etc., Although the Chi-square
test was used to compare observed and expected results, nothing was mentioned in the statistical
analysis section.
16. Ensure that table captions succinctly describe the content for standalone clarity.
17. Some findings are repeated in text, tables, and figures. Instead, summarize key trends.
18. The LFI’s correlation with platelet count, total bile acid, and ammonia should be explained
in clinical terms.
In the Discussion section:
19. The discussion section is one of the final parts of a research paper, in which an author
describes, analyzes, and interprets their findings. They explain the significance of those results
and tie everything back to the research question(s). In this manuscript, there is confusion
between what should be written in the introduction and discussion sections. Please reconstruct
the discussion section.
20. Expand on clinical relevance to discuss how should SE be used in practice as a screening
tool, a monitoring method, or a diagnostic replacement for biopsy.
21.  Expand study limitations more explicitly: Small sample size limits generalizability,
retrospective nature may introduce selection bias and lack of liver biopsy data for direct fibrosis
validation.
22. Compare findings with international studies to show if SE performs better or worse than
MRE, SWE, or TE in similar FALD populations.
Title: Strain Elastography for Detecting Advanced Fontan-Associated Liver Disease: A
Retrospective Study
Version: 1 Date: 23 Mar 2025
Reviewer:  Amira A. A. Othman
Reviewer's report:
First of all
I want to congratulate the authors on their work. In this study, Imoto et al. aimed to evaluate the
effectiveness of non-invasive tests (NITs), particularly strain elastography (SE), in identifying
advanced Fontan-associated liver disease (a FALD). It compares SE’s diagnostic accuracy with
established fibrosis markers, platelet counts, and other elastography techniques. By analyzing
data from Fontan patients at Kyushu University Hospital, the study aims to determine whether
SE-derived liver fibrosis index (LFI) improves the detection of a FALD, which is crucial for
risk stratification and clinical management.
The authors handled the reviewer comments satisfactorily, nevertheless, there is an observation
for which sufficient justification must be obtained.
In general:
1. The language is generally clear, but some minor grammatical errors and awkward phrasings
could be improved. Consider having the manuscript proofread by a native English speaker or
a professional editing service.
2. Abbreviations must be fully written at their first appearance.
In Title:
1. The title is somewhat long and could be more direct. , I suggest “ Strain Elastography for
Detecting Advanced Fontan-Associated Liver Disease: a retrospective study”.
In Abstract section
2. The background subsection in the abstract :
-  Should be the shortest part of the abstract. It should briefly outline the following information:
What is already known about the subject, related to the paper in question. What is not known
about the subject and hence what the study intended to examine (or what the paper seeks to
present)? Avoid redundancy:
- The NITs vs. SE comparison is repeated multiple times
-  What does SE’s accuracy mean for patient management and follow-up?.
- Add a brief statement on how SE can impact clinical decisions.
3. In the method subsection in the abstract :
- Nothing was mentioned about the participant's age, sex, ethnicity, etc.
- It would help if you described the aim of your statistical analysis.
4. In the results subsection in the abstract :
-   Improve numerical clarity and conciseness
5. In the conclusion subsection in the abstract :
- Emphasize the clinical significance of your study: "What does SE’s accuracy mean for patient
management and follow-up?”
In the Introduction section:
6. Avoid excessive background on the Fontan procedure: The discussion on systemic venous
return and cardiac physiology could be shortened.
7. The transition from elastography techniques to SE’s potential advantages should be smoother.
8. Clarify the research gap; prior studies have assessed other elastography methods (MRE, SWE,
TE)—why focus specifically on SE?
In the Methods section:
9. Please provide the participants' sociodemographic data well.
10. How the sample size was calculated. Was a power calculation performed?
11. Explain the choice of cut-off values; how were the LFI and platelet count thresholds
determined?
12. Did patients have other liver conditions (e.g., metabolic or viral liver diseases)?
13. How did medications, age, or Fontan circulation duration impact fibrosis assessment?
In the Results section:
14. In all tables, please explain the abbreviations under tables.
15. You can title the statistical test column as “Test of significance” and use U= for the Mann–
Whitney U test, T= for the T-test, and #2 = for the Chi-square test, etc., Although the Chi-square
test was used to compare observed and expected results, nothing was mentioned in the statistical
analysis section.
16. Ensure that table captions succinctly describe the content for standalone clarity.
17. Some findings are repeated in text, tables, and figures. Instead, summarize key trends.
18. The LFI’s correlation with platelet count, total bile acid, and ammonia should be explained
in clinical terms.
In the Discussion section:
19. The discussion section is one of the final parts of a research paper, in which an author
describes, analyzes, and interprets their findings. They explain the significance of those results
and tie everything back to the research question(s). In this manuscript, there is confusion
between what should be written in the introduction and discussion sections. Please reconstruct
the discussion section.
20. Expand on clinical relevance to discuss how should SE be used in practice as a screening
tool, a monitoring method, or a diagnostic replacement for biopsy.
21.  Expand study limitations more explicitly: Small sample size limits generalizability,
retrospective nature may introduce selection bias and lack of liver biopsy data for direct fibrosis
validation.
22. Compare findings with international studies to show if SE performs better or worse than
MRE, SWE, or TE in similar FALD populations.
Please review this paper.
user
Title: Strain Elastography for Detecting Advanced Fontan-Associated Liver Disease: A
Retrospective Study
Version: 1 Date: 23 Mar 2025
Reviewer:  Amira A. A. Othman
Reviewer's report:
First of all
I want to congratulate the authors on their work. In this study, Imoto et al. aimed to evaluate the
effectiveness of non-invasive tests (NITs), particularly strain elastography (SE), in identifying
advanced Fontan-associated liver disease (a FALD). It compares SE’s diagnostic accuracy with
established fibrosis markers, platelet counts, and other elastography techniques. By analyzing
data from Fontan patients at Kyushu University Hospital, the study aims to determine whether
SE-derived liver fibrosis index (LFI) improves the detection of a FALD, which is crucial for
risk stratification and clinical management.
The authors handled the reviewer comments satisfactorily, nevertheless, there is an observation
for which sufficient justification must be obtained.
In general:
1. The language is generally clear, but some minor grammatical errors and awkward phrasings
could be improved. Consider having the manuscript proofread by a native English speaker or
a professional editing service.
2. Abbreviations must be fully written at their first appearance.
In Title:
1. The title is somewhat long and could be more direct. , I suggest “ Strain Elastography for
Detecting Advanced Fontan-Associated Liver Disease: a retrospective study”.
In Abstract section
2. The background subsection in the abstract :
-  Should be the shortest part of the abstract. It should briefly outline the following information:
What is already known about the subject, related to the paper in question. What is not known
about the subject and hence what the study intended to examine (or what the paper seeks to
present)? Avoid redundancy:
- The NITs vs. SE comparison is repeated multiple times
-  What does SE’s accuracy mean for patient management and follow-up?.
- Add a brief statement on how SE can impact clinical decisions.
3. In the method subsection in the abstract :
- Nothing was mentioned about the participant's age, sex, ethnicity, etc.
- It would help if you described the aim of your statistical analysis.
4. In the results subsection in the abstract :
-   Improve numerical clarity and conciseness
5. In the conclusion subsection in the abstract :
- Emphasize the clinical significance of your study: "What does SE’s accuracy mean for patient
management and follow-up?”
In the Introduction section:
6. Avoid excessive background on the Fontan procedure: The discussion on systemic venous
return and cardiac physiology could be shortened.
7. The transition from elastography techniques to SE’s potential advantages should be smoother.
8. Clarify the research gap; prior studies have assessed other elastography methods (MRE, SWE,
TE)—why focus specifically on SE?
In the Methods section:
9. Please provide the participants' sociodemographic data well.
10. How the sample size was calculated. Was a power calculation performed?
11. Explain the choice of cut-off values; how were the LFI and platelet count thresholds
determined?
12. Did patients have other liver conditions (e.g., metabolic or viral liver diseases)?
13. How did medications, age, or Fontan circulation duration impact fibrosis assessment?
In the Results section:
14. In all tables, please explain the abbreviations under tables.
15. You can title the statistical test column as “Test of significance” and use U= for the Mann–
Whitney U test, T= for the T-test, and #2 = for the Chi-square test, etc., Although the Chi-square
test was used to compare observed and expected results, nothing was mentioned in the statistical
analysis section.
16. Ensure that table captions succinctly describe the content for standalone clarity.
17. Some findings are repeated in text, tables, and figures. Instead, summarize key trends.
18. The LFI’s correlation with platelet count, total bile acid, and ammonia should be explained
in clinical terms.
In the Discussion section:
19. The discussion section is one of the final parts of a research paper, in which an author
describes, analyzes, and interprets their findings. They explain the significance of those results
and tie everything back to the research question(s). In this manuscript, there is confusion
between what should be written in the introduction and discussion sections. Please reconstruct
the discussion section.
20. Expand on clinical relevance to discuss how should SE be used in practice as a screening
tool, a monitoring method, or a diagnostic replacement for biopsy.
21.  Expand study limitations more explicitly: Small sample size limits generalizability,
retrospective nature may introduce selection bias and lack of liver biopsy data for direct fibrosis
validation.
22. Compare findings with international studies to show if SE performs better or worse than
MRE, SWE, or TE in similar FALD populations.
assistant