Reviewer’s report
Title: 
Prognosis of liver transplantation: Does postoperative ileus matter ?
Version: 
0 
Date: 
19 Apr 2021
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses a
testable research question(s) (brief or other article types: is there a clear
objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols)
appropriate for the objective?
No - there are minor issues
EXECUTION - Are the experiments and analyses performed with technical rigor
to allow confidence in the results?
No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results
reasonable and not overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work
technically sound? If not, can revisions be made to make the work technically
sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: 
The manuscript entitled "Prognosis of liver transplantation: Does postoperative
ileus matter?" is a retrospective cohort study evaluating the impact of
postoperative ileus (incidence = 23.2%) on patient survival after liver
transplantation. The authors included and analyzed over 30 variables (including
preoperative, intraoperative, and postoperative) to identify factors that may
impact the incidence of postoperative ileus. Overall, the authors found no
difference in overall post-transplantation survival between patients with and
without postoperative ileus. There was no difference in the incidence of
postoperative complications between these same groups reported. And no key
factors were associated with the risk of postoperative ileus in the overall cohort.
REQUESTED REVISIONS: 
The manuscript would be enhanced by addressing some study design issues as
well as making several organizational changes in the methods section. Regarding
study design, I recommend the authors include information regarding commonly
known factors that increase the risk of postoperative ileus - extended immobility,
narcotic or non-dihydropyridine calcium channel blocker use, prolonged use of
foley catheter, drains and/or nasogastric tube, and delayed enteral feeding.
Addressing these key areas is a common part of an enhanced recovery after
surgery program. 
Another design issue relates to the post-transplantation survival analysis. I
believe the authors' hypothesis is that postoperative ileus may increase incidence
of complications and lower overall survival post-transplantation. I suggest the
authors specify the time frame that they assessed for complications in the
postoperative period. A typical time frame may be within 30 days of surgery or
30 days of diagnosis of postoperative ileus. Additionally, overall survival should
be limited to one year to better highlight the potential impact of ileus on survival.
It is unlikely that an ileus on postoperative day 4 would have an impact on
survival at postoperative day 999. Their extended survival analysis out to 5 years
post-transplantation may have limited their ability to detect a small but
meaningful difference early on. 
Finally, the authors appropriately looked at donor characteristics in this study.
They should consider using the donor risk index, including variables such as
donation after cardiac death, in their study. The donor risk index for liver
transplantation is well-validated and known to impact overall survival post-
transplantation. 
The methods section will be enhanced by additional detail and organization. The
use of subsections is good but the authors could add more. The initial subsection
could describe from where their data collection occurred. Additionally,
information regarding inclusion/exclusion criteria would go here. Another
subsection should be dedicated to describing the actual data collected (i.e. -
preoperative, intraoperative, and postoperative). The authors should consider
explaining why certain factors were chosen or include a reference describing
their association with postoperative ileus or survival. Moreover, the authors
should specify at what time point in days the preoperative or postoperative
variables, such as weight and laboratory findings, were analyzed. In the methods,
the authors should discuss how they confirmed survival (alive or deceased) data
for their included patients. And they should also specify if survival was
calculated from the day of surgery, day after surgery, or from when
postoperative ileus was diagnosed. Another subsection should describe the
general perioperative care for their post-transplantation patients. This section
could also address how often drains/catheters are used as well as attempts at
early mobilization and enteral feeding. Another section should describe how they
will define complications prior to their chart review and during what time period
complications will be assessed. The authors should consider including re-
admission within 30 (or 90) days and reoperations as additional complications to
assess. And finally, the methods section would conclude with the plans for
statistical analysis. 
I am not sure that the subgroup analysis of the HBV and HCC cohorts adds
much to the manuscript. I recommend the authors describe why they chose to
perform this analysis. Additionally, if the authors include the analysis in the
manuscript, then I recommend they consider describing a hypothesis as to why a
lower MELD score was associated with more postoperative ileus in the HBV
subgroup.
ADDITIONAL REQUESTS/SUGGESTIONS: 
The tables are not called out in consecutive order in the manuscript. The authors
should reorganize the tables so that they are called out in the manuscript in
consecutive order.
There is a recurring spelling mistake in the tables (e.g., Table 2, "vascular
complication") that should be corrected.
For the figure, I recommend changing the y-axis label to "overall survival (%)"
to enhance the clarity of the figure on its own.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
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find the details of processing in Publons’ privacy policy
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No
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square.
Reviewers with declared or apparent competing interests are not utilized for
these reviews. This reviewer has agreed to publication of their comments online
under a Creative Commons Attribution License attributed to Research Square
and was paid a small honorarium for completing the review within a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Prognosis of liver transplantation: Does postoperative ileus matter ?
Version: 
0 
Date: 
19 Apr 2021
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses a
testable research question(s) (brief or other article types: is there a clear
objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols)
appropriate for the objective?
No - there are minor issues
EXECUTION - Are the experiments and analyses performed with technical rigor
to allow confidence in the results?
No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results
reasonable and not overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work
technically sound? If not, can revisions be made to make the work technically
sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: 
The manuscript entitled "Prognosis of liver transplantation: Does postoperative
ileus matter?" is a retrospective cohort study evaluating the impact of
postoperative ileus (incidence = 23.2%) on patient survival after liver
transplantation. The authors included and analyzed over 30 variables (including
preoperative, intraoperative, and postoperative) to identify factors that may
impact the incidence of postoperative ileus. Overall, the authors found no
difference in overall post-transplantation survival between patients with and
without postoperative ileus. There was no difference in the incidence of
postoperative complications between these same groups reported. And no key
factors were associated with the risk of postoperative ileus in the overall cohort.
REQUESTED REVISIONS: 
The manuscript would be enhanced by addressing some study design issues as
well as making several organizational changes in the methods section. Regarding
study design, I recommend the authors include information regarding commonly
known factors that increase the risk of postoperative ileus - extended immobility,
narcotic or non-dihydropyridine calcium channel blocker use, prolonged use of
foley catheter, drains and/or nasogastric tube, and delayed enteral feeding.
Addressing these key areas is a common part of an enhanced recovery after
surgery program. 
Another design issue relates to the post-transplantation survival analysis. I
believe the authors' hypothesis is that postoperative ileus may increase incidence
of complications and lower overall survival post-transplantation. I suggest the
authors specify the time frame that they assessed for complications in the
postoperative period. A typical time frame may be within 30 days of surgery or
30 days of diagnosis of postoperative ileus. Additionally, overall survival should
be limited to one year to better highlight the potential impact of ileus on survival.
It is unlikely that an ileus on postoperative day 4 would have an impact on
survival at postoperative day 999. Their extended survival analysis out to 5 years
post-transplantation may have limited their ability to detect a small but
meaningful difference early on. 
Finally, the authors appropriately looked at donor characteristics in this study.
They should consider using the donor risk index, including variables such as
donation after cardiac death, in their study. The donor risk index for liver
transplantation is well-validated and known to impact overall survival post-
transplantation. 
The methods section will be enhanced by additional detail and organization. The
use of subsections is good but the authors could add more. The initial subsection
could describe from where their data collection occurred. Additionally,
information regarding inclusion/exclusion criteria would go here. Another
subsection should be dedicated to describing the actual data collected (i.e. -
preoperative, intraoperative, and postoperative). The authors should consider
explaining why certain factors were chosen or include a reference describing
their association with postoperative ileus or survival. Moreover, the authors
should specify at what time point in days the preoperative or postoperative
variables, such as weight and laboratory findings, were analyzed. In the methods,
the authors should discuss how they confirmed survival (alive or deceased) data
for their included patients. And they should also specify if survival was
calculated from the day of surgery, day after surgery, or from when
postoperative ileus was diagnosed. Another subsection should describe the
general perioperative care for their post-transplantation patients. This section
could also address how often drains/catheters are used as well as attempts at
early mobilization and enteral feeding. Another section should describe how they
will define complications prior to their chart review and during what time period
complications will be assessed. The authors should consider including re-
admission within 30 (or 90) days and reoperations as additional complications to
assess. And finally, the methods section would conclude with the plans for
statistical analysis. 
I am not sure that the subgroup analysis of the HBV and HCC cohorts adds
much to the manuscript. I recommend the authors describe why they chose to
perform this analysis. Additionally, if the authors include the analysis in the
manuscript, then I recommend they consider describing a hypothesis as to why a
lower MELD score was associated with more postoperative ileus in the HBV
subgroup.
ADDITIONAL REQUESTS/SUGGESTIONS: 
The tables are not called out in consecutive order in the manuscript. The authors
should reorganize the tables so that they are called out in the manuscript in
consecutive order.
There is a recurring spelling mistake in the tables (e.g., Table 2, "vascular
complication") that should be corrected.
For the figure, I recommend changing the y-axis label to "overall survival (%)"
to enhance the clarity of the figure on its own.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
No
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square.
Reviewers with declared or apparent competing interests are not utilized for
these reviews. This reviewer has agreed to publication of their comments online
under a Creative Commons Attribution License attributed to Research Square
and was paid a small honorarium for completing the review within a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Prognosis of liver transplantation: Does postoperative ileus matter ?
Version: 
0 
Date: 
19 Apr 2021
Reviewer's report:
PEER REVIEWER ASSESSMENTS: 
OBJECTIVE - Full research articles: is there a clear objective that addresses a
testable research question(s) (brief or other article types: is there a clear
objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols)
appropriate for the objective?
No - there are minor issues
EXECUTION - Are the experiments and analyses performed with technical rigor
to allow confidence in the results?
No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results
reasonable and not overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work
technically sound? If not, can revisions be made to make the work technically
sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS: 
GENERAL COMMENTS: 
The manuscript entitled "Prognosis of liver transplantation: Does postoperative
ileus matter?" is a retrospective cohort study evaluating the impact of
postoperative ileus (incidence = 23.2%) on patient survival after liver
transplantation. The authors included and analyzed over 30 variables (including
preoperative, intraoperative, and postoperative) to identify factors that may
impact the incidence of postoperative ileus. Overall, the authors found no
difference in overall post-transplantation survival between patients with and
without postoperative ileus. There was no difference in the incidence of
postoperative complications between these same groups reported. And no key
factors were associated with the risk of postoperative ileus in the overall cohort.
REQUESTED REVISIONS: 
The manuscript would be enhanced by addressing some study design issues as
well as making several organizational changes in the methods section. Regarding
study design, I recommend the authors include information regarding commonly
known factors that increase the risk of postoperative ileus - extended immobility,
narcotic or non-dihydropyridine calcium channel blocker use, prolonged use of
foley catheter, drains and/or nasogastric tube, and delayed enteral feeding.
Addressing these key areas is a common part of an enhanced recovery after
surgery program. 
Another design issue relates to the post-transplantation survival analysis. I
believe the authors' hypothesis is that postoperative ileus may increase incidence
of complications and lower overall survival post-transplantation. I suggest the
authors specify the time frame that they assessed for complications in the
postoperative period. A typical time frame may be within 30 days of surgery or
30 days of diagnosis of postoperative ileus. Additionally, overall survival should
be limited to one year to better highlight the potential impact of ileus on survival.
It is unlikely that an ileus on postoperative day 4 would have an impact on
survival at postoperative day 999. Their extended survival analysis out to 5 years
post-transplantation may have limited their ability to detect a small but
meaningful difference early on. 
Finally, the authors appropriately looked at donor characteristics in this study.
They should consider using the donor risk index, including variables such as
donation after cardiac death, in their study. The donor risk index for liver
transplantation is well-validated and known to impact overall survival post-
transplantation. 
The methods section will be enhanced by additional detail and organization. The
use of subsections is good but the authors could add more. The initial subsection
could describe from where their data collection occurred. Additionally,
information regarding inclusion/exclusion criteria would go here. Another
subsection should be dedicated to describing the actual data collected (i.e. -
preoperative, intraoperative, and postoperative). The authors should consider
explaining why certain factors were chosen or include a reference describing
their association with postoperative ileus or survival. Moreover, the authors
should specify at what time point in days the preoperative or postoperative
variables, such as weight and laboratory findings, were analyzed. In the methods,
the authors should discuss how they confirmed survival (alive or deceased) data
for their included patients. And they should also specify if survival was
calculated from the day of surgery, day after surgery, or from when
postoperative ileus was diagnosed. Another subsection should describe the
general perioperative care for their post-transplantation patients. This section
could also address how often drains/catheters are used as well as attempts at
early mobilization and enteral feeding. Another section should describe how they
will define complications prior to their chart review and during what time period
complications will be assessed. The authors should consider including re-
admission within 30 (or 90) days and reoperations as additional complications to
assess. And finally, the methods section would conclude with the plans for
statistical analysis. 
I am not sure that the subgroup analysis of the HBV and HCC cohorts adds
much to the manuscript. I recommend the authors describe why they chose to
perform this analysis. Additionally, if the authors include the analysis in the
manuscript, then I recommend they consider describing a hypothesis as to why a
lower MELD score was associated with more postoperative ileus in the HBV
subgroup.
ADDITIONAL REQUESTS/SUGGESTIONS: 
The tables are not called out in consecutive order in the manuscript. The authors
should reorganize the tables so that they are called out in the manuscript in
consecutive order.
There is a recurring spelling mistake in the tables (e.g., Table 2, "vascular
complication") that should be corrected.
For the figure, I recommend changing the y-axis label to "overall survival (%)"
to enhance the clarity of the figure on its own.
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
No
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
This reviewer has been recruited by a partner organization, Research Square.
Reviewers with declared or apparent competing interests are not utilized for
these reviews. This reviewer has agreed to publication of their comments online
under a Creative Commons Attribution License attributed to Research Square
and was paid a small honorarium for completing the review within a specified
timeframe. Honoraria for reviews such as this are paid regardless of the reviewer
recommendation.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
Are the methods sufficiently described to allow the study to be repeated?
No
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
No
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
assistant