Reviewer ’s report  
 
Title:  A subclinical high tricuspid regurgitation pressure gradient independent of the mean 
pulmonary artery pressure is a risk factor for the survival afte r living donor liver transplantation  
 
Version: 1 Date: 14 Dec 2017 
 
Reviewer:  Lukas  Unger  
 
Reviewer’s report:  
 
Comments to the Author  
 
The study by Saragai et al. investigates the impact of portopulmonary hypertension on 
postoperative survival in living related liver transplantation. The authors utilize the peak systolic 
tricuspid  regurgitation pressure gradient measured by transthoracic echocardiography to estimate 
portal hypertension related congestive pressure and demonstrate that a subclinical high TRPG is 
associated with worse survival post LDLT. The study is well -written and addresses an important 
clinical problem.  
 
Interstingly, the authors show that high mPAP immediately before surgery and after general 
anesthesia does not affect post -OLT outcome and TRPG assessed by echocardiography before 
general anesthesia, has a better pr ognostic value. In conclusion, mPAP assessment at the time of 
OLT might be considered unnecessary as 1) no specific therapy can be initiated at this time point 
and 2) there is no clinical consequence of high mPAP.  
 
 
Specific comments:  
 
1.) The AASLD Pr actice Guidelines (PMID: 24716201) should be referenced on page 7 line 
20 as the authors write "Furthermore, the Practice Guidelines recommend that patients 
with mPAP < 35 mmHg be indicated for OLT, and PA -targeted therapy should be 
initiated in patients w ith mPAP ≥ 35 mmHg." but no reference is included.  
 
2.) The prospective nature of the study should be mentioned in the abstract.  
 
3.) The nomenclature of "subclinical" and "non -subclincal" should be revised. Could the 
groups potentially be re -named a s e.g. "subclinical HPS" and "no -HPS" and "subclinical 
high TRPG" and "low/normal TRPG"?  
 
4.) The severity of portal hypertension, e.g. measured by hepatic venous pressure gradient, 
might influence the POPH. Therefore, results of portal hypertension eva luation in 
addition to MELD scores should be included in the manuscript, if available.  
 
5.) P-values should be added to the paragraph and not only to the Tables/figures (e.g. on 
page 12, line 36)  
6.) No information on peri or postoperative kidney di sease is available in the study.  
However, serum -creatinine values should be included in the postoperative clinical course 
and correlation between pre -OP echocardiography results and post -OP kidney function 
should be added, as prior studies in deceased don or liver transplantation have shown a 
correlation between e.g. LVEF and risk for post -transplant CKD risk.  
 
7.) The authors identify subclinical high TRPG as important factor for postoperative 
survival. Figure 1 A and B should be removed to avoid distra ction, as the information is 
included in Figure 1 C. The same comments apply for figure 2. In Figure 2, a Figure 
legend indicating the subgroups should be added in addition the the figure legend.  
 
8.) The finding that a high mPAP does not affect post -operative survival should be included 
in the title, as it is a main finding of the study. "A subclinical high tricuspid regurgitation 
pressure gradient independent of the mean pulmonary artery pressure is a risk factor for 
survival after living donor liver t ransplantation".  
 
9.) The authors suggest that the co -existence of HPS may relieve the TR pressure. This is 
only a suggestion and should be removed from the conclusion section.  
 
10.) As the sample size is relatively low, the need for larger studies confi rming their results 
should be mentioned in the conclusion as well as the discussion section.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include t he necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to  assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
Acceptable  
 
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 organisat ion 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.  
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I ag ree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be inc luded in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title:  A subclinical high tricuspid regurgitation pressure gradient independent of the mean 
pulmonary artery pressure is a risk factor for the survival afte r living donor liver transplantation  
 
Version: 1 Date: 14 Dec 2017 
 
Reviewer:  Lukas  Unger  
 
Reviewer’s report:  
 
Comments to the Author  
 
The study by Saragai et al. investigates the impact of portopulmonary hypertension on 
postoperative survival in living related liver transplantation. The authors utilize the peak systolic 
tricuspid  regurgitation pressure gradient measured by transthoracic echocardiography to estimate 
portal hypertension related congestive pressure and demonstrate that a subclinical high TRPG is 
associated with worse survival post LDLT. The study is well -written and addresses an important 
clinical problem.  
 
Interstingly, the authors show that high mPAP immediately before surgery and after general 
anesthesia does not affect post -OLT outcome and TRPG assessed by echocardiography before 
general anesthesia, has a better pr ognostic value. In conclusion, mPAP assessment at the time of 
OLT might be considered unnecessary as 1) no specific therapy can be initiated at this time point 
and 2) there is no clinical consequence of high mPAP.  
 
 
Specific comments:  
 
1.) The AASLD Pr actice Guidelines (PMID: 24716201) should be referenced on page 7 line 
20 as the authors write "Furthermore, the Practice Guidelines recommend that patients 
with mPAP < 35 mmHg be indicated for OLT, and PA -targeted therapy should be 
initiated in patients w ith mPAP ≥ 35 mmHg." but no reference is included.  
 
2.) The prospective nature of the study should be mentioned in the abstract.  
 
3.) The nomenclature of "subclinical" and "non -subclincal" should be revised. Could the 
groups potentially be re -named a s e.g. "subclinical HPS" and "no -HPS" and "subclinical 
high TRPG" and "low/normal TRPG"?  
 
4.) The severity of portal hypertension, e.g. measured by hepatic venous pressure gradient, 
might influence the POPH. Therefore, results of portal hypertension eva luation in 
addition to MELD scores should be included in the manuscript, if available.  
 
5.) P-values should be added to the paragraph and not only to the Tables/figures (e.g. on 
page 12, line 36)  
6.) No information on peri or postoperative kidney di sease is available in the study.  
However, serum -creatinine values should be included in the postoperative clinical course 
and correlation between pre -OP echocardiography results and post -OP kidney function 
should be added, as prior studies in deceased don or liver transplantation have shown a 
correlation between e.g. LVEF and risk for post -transplant CKD risk.  
 
7.) The authors identify subclinical high TRPG as important factor for postoperative 
survival. Figure 1 A and B should be removed to avoid distra ction, as the information is 
included in Figure 1 C. The same comments apply for figure 2. In Figure 2, a Figure 
legend indicating the subgroups should be added in addition the the figure legend.  
 
8.) The finding that a high mPAP does not affect post -operative survival should be included 
in the title, as it is a main finding of the study. "A subclinical high tricuspid regurgitation 
pressure gradient independent of the mean pulmonary artery pressure is a risk factor for 
survival after living donor liver t ransplantation".  
 
9.) The authors suggest that the co -existence of HPS may relieve the TR pressure. This is 
only a suggestion and should be removed from the conclusion section.  
 
10.) As the sample size is relatively low, the need for larger studies confi rming their results 
should be mentioned in the conclusion as well as the discussion section.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include t he necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to  assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
Acceptable  
 
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 organisat ion 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.  
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I ag ree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be inc luded in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title:  A subclinical high tricuspid regurgitation pressure gradient independent of the mean 
pulmonary artery pressure is a risk factor for the survival afte r living donor liver transplantation  
 
Version: 1 Date: 14 Dec 2017 
 
Reviewer:  Lukas  Unger  
 
Reviewer’s report:  
 
Comments to the Author  
 
The study by Saragai et al. investigates the impact of portopulmonary hypertension on 
postoperative survival in living related liver transplantation. The authors utilize the peak systolic 
tricuspid  regurgitation pressure gradient measured by transthoracic echocardiography to estimate 
portal hypertension related congestive pressure and demonstrate that a subclinical high TRPG is 
associated with worse survival post LDLT. The study is well -written and addresses an important 
clinical problem.  
 
Interstingly, the authors show that high mPAP immediately before surgery and after general 
anesthesia does not affect post -OLT outcome and TRPG assessed by echocardiography before 
general anesthesia, has a better pr ognostic value. In conclusion, mPAP assessment at the time of 
OLT might be considered unnecessary as 1) no specific therapy can be initiated at this time point 
and 2) there is no clinical consequence of high mPAP.  
 
 
Specific comments:  
 
1.) The AASLD Pr actice Guidelines (PMID: 24716201) should be referenced on page 7 line 
20 as the authors write "Furthermore, the Practice Guidelines recommend that patients 
with mPAP < 35 mmHg be indicated for OLT, and PA -targeted therapy should be 
initiated in patients w ith mPAP ≥ 35 mmHg." but no reference is included.  
 
2.) The prospective nature of the study should be mentioned in the abstract.  
 
3.) The nomenclature of "subclinical" and "non -subclincal" should be revised. Could the 
groups potentially be re -named a s e.g. "subclinical HPS" and "no -HPS" and "subclinical 
high TRPG" and "low/normal TRPG"?  
 
4.) The severity of portal hypertension, e.g. measured by hepatic venous pressure gradient, 
might influence the POPH. Therefore, results of portal hypertension eva luation in 
addition to MELD scores should be included in the manuscript, if available.  
 
5.) P-values should be added to the paragraph and not only to the Tables/figures (e.g. on 
page 12, line 36)  
6.) No information on peri or postoperative kidney di sease is available in the study.  
However, serum -creatinine values should be included in the postoperative clinical course 
and correlation between pre -OP echocardiography results and post -OP kidney function 
should be added, as prior studies in deceased don or liver transplantation have shown a 
correlation between e.g. LVEF and risk for post -transplant CKD risk.  
 
7.) The authors identify subclinical high TRPG as important factor for postoperative 
survival. Figure 1 A and B should be removed to avoid distra ction, as the information is 
included in Figure 1 C. The same comments apply for figure 2. In Figure 2, a Figure 
legend indicating the subgroups should be added in addition the the figure legend.  
 
8.) The finding that a high mPAP does not affect post -operative survival should be included 
in the title, as it is a main finding of the study. "A subclinical high tricuspid regurgitation 
pressure gradient independent of the mean pulmonary artery pressure is a risk factor for 
survival after living donor liver t ransplantation".  
 
9.) The authors suggest that the co -existence of HPS may relieve the TR pressure. This is 
only a suggestion and should be removed from the conclusion section.  
 
10.) As the sample size is relatively low, the need for larger studies confi rming their results 
should be mentioned in the conclusion as well as the discussion section.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include t he necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to  assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
Acceptable  
 
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 organisat ion 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.  
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I ag ree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be inc luded in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant