Reviewer’s report  
Title: Liver and spleen transient elastography predicts portal hypertension in patients with 
chronic  liver disease: a prospective cohort study  
 
Version: 0 Date: 10 Sep 2015  
 
Reviewer: Srinivasan  Dasarathy  
Reviewer’s report:  
This is a prospective study in 107 patients with chronic liver diseases showed that transient liver 
elastrography was able to predict significant and severe portal hypertension with reasonably 
good specificity and sensitivity.  
 
A number of major concerns limit enthusiasm:  
 
1. The patient population characteristics are not described in sufficient detail. How many 
patients had cirrhosis? Was a liver biopsy done in these patients? What was the severity 
of fibrosis, lobular inflammation and hepatocyte necrosis in these subjects? All patients 
had TJ pressure studies, so it is presumed that they had a biopsy evaluation of the liver 
done.  
 
2. The rationale is not clear. The authors describe clinically significant and severe portal 
hypertension based on wedge pressures. However, why was th e TJ pressure study done? 
Was this purely for research? If so, then the difference between clinically significant and 
severe is only 2 mm (≥10mm Hg. For CSPH and ≥12mm for severe portal hypertension). 
This is very concerning, the difference between CSPH an d severe portal hypertension is 
only 2 mm. The authors comment on the intraobserver reproducibility (page 5, line 115 - 
mean of 3 readings and if difference between readings was >1mm Hg, new readings were 
taken). This introduces bias, questions the relia bility of classifying patients into CSPH 
and severe portal hypertension and for accuracy, a more sensitive measure using cm. 
saline could have been used. The difference of 1 mm, i.e. 11mm (CSPH) and 12 mm 
(severe portal hypertension) will be very difficult  to interpret. When 3 readings were 
obtained, how many times did the investigators have to cancel the prior readings and 
repeat the measurements? How much time was taken for these measurements. Finally, 
and of most concern, how many subjects had no portal hypertension or portal pressure 
<10 mm Hg. and how was that data analyzed?  
 
3. The box and whisker plot figures show significant overlap between the values of the 
stiffness. A scatterplot with mean and standard deviation maybe a better representation.  
 
4. Interpretation and conclusions. Given the modest sensitivity and specificity, the data 
shows that higher values suggest severe portal hypertension while lower liver stiffness 
values do not necessarily exclude severe portal hypertension.  
 
 
5. A few typograp hical errors - need careful review of manuscript for English language. Eg 
page 9, line 17 not "have no", should be "has no" but please review, there are others that 
are not listed here.  
 
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.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
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 asses s the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, consid ering 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, e ither now or in the future?  
 
2. Do yo u hold any stocks or shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, e ither now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the  content of the 
manu script?  
 
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 fin ancial competing interests?  
 
6. Do you have any non -financial c ompeting 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 al ong with the authors' 
responses. 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/ ). I understand that an y comments 
which I do not wish to be included 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: Liver and spleen transient elastography predicts portal hypertension in patients with 
chronic  liver disease: a prospective cohort study  
 
Version: 0 Date: 10 Sep 2015  
 
Reviewer: Srinivasan  Dasarathy  
Reviewer’s report:  
This is a prospective study in 107 patients with chronic liver diseases showed that transient liver 
elastrography was able to predict significant and severe portal hypertension with reasonably 
good specificity and sensitivity.  
 
A number of major concerns limit enthusiasm:  
 
1. The patient population characteristics are not described in sufficient detail. How many 
patients had cirrhosis? Was a liver biopsy done in these patients? What was the severity 
of fibrosis, lobular inflammation and hepatocyte necrosis in these subjects? All patients 
had TJ pressure studies, so it is presumed that they had a biopsy evaluation of the liver 
done.  
 
2. The rationale is not clear. The authors describe clinically significant and severe portal 
hypertension based on wedge pressures. However, why was th e TJ pressure study done? 
Was this purely for research? If so, then the difference between clinically significant and 
severe is only 2 mm (≥10mm Hg. For CSPH and ≥12mm for severe portal hypertension). 
This is very concerning, the difference between CSPH an d severe portal hypertension is 
only 2 mm. The authors comment on the intraobserver reproducibility (page 5, line 115 - 
mean of 3 readings and if difference between readings was >1mm Hg, new readings were 
taken). This introduces bias, questions the relia bility of classifying patients into CSPH 
and severe portal hypertension and for accuracy, a more sensitive measure using cm. 
saline could have been used. The difference of 1 mm, i.e. 11mm (CSPH) and 12 mm 
(severe portal hypertension) will be very difficult  to interpret. When 3 readings were 
obtained, how many times did the investigators have to cancel the prior readings and 
repeat the measurements? How much time was taken for these measurements. Finally, 
and of most concern, how many subjects had no portal hypertension or portal pressure 
<10 mm Hg. and how was that data analyzed?  
 
3. The box and whisker plot figures show significant overlap between the values of the 
stiffness. A scatterplot with mean and standard deviation maybe a better representation.  
 
4. Interpretation and conclusions. Given the modest sensitivity and specificity, the data 
shows that higher values suggest severe portal hypertension while lower liver stiffness 
values do not necessarily exclude severe portal hypertension.  
 
 
5. A few typograp hical errors - need careful review of manuscript for English language. Eg 
page 9, line 17 not "have no", should be "has no" but please review, there are others that 
are not listed here.  
 
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.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
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 asses s the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, consid ering 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, e ither now or in the future?  
 
2. Do yo u hold any stocks or shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, e ither now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the  content of the 
manu script?  
 
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 fin ancial competing interests?  
 
6. Do you have any non -financial c ompeting 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 al ong with the authors' 
responses. 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/ ). I understand that an y comments 
which I do not wish to be included 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: Liver and spleen transient elastography predicts portal hypertension in patients with 
chronic  liver disease: a prospective cohort study  
 
Version: 0 Date: 10 Sep 2015  
 
Reviewer: Srinivasan  Dasarathy  
Reviewer’s report:  
This is a prospective study in 107 patients with chronic liver diseases showed that transient liver 
elastrography was able to predict significant and severe portal hypertension with reasonably 
good specificity and sensitivity.  
 
A number of major concerns limit enthusiasm:  
 
1. The patient population characteristics are not described in sufficient detail. How many 
patients had cirrhosis? Was a liver biopsy done in these patients? What was the severity 
of fibrosis, lobular inflammation and hepatocyte necrosis in these subjects? All patients 
had TJ pressure studies, so it is presumed that they had a biopsy evaluation of the liver 
done.  
 
2. The rationale is not clear. The authors describe clinically significant and severe portal 
hypertension based on wedge pressures. However, why was th e TJ pressure study done? 
Was this purely for research? If so, then the difference between clinically significant and 
severe is only 2 mm (≥10mm Hg. For CSPH and ≥12mm for severe portal hypertension). 
This is very concerning, the difference between CSPH an d severe portal hypertension is 
only 2 mm. The authors comment on the intraobserver reproducibility (page 5, line 115 - 
mean of 3 readings and if difference between readings was >1mm Hg, new readings were 
taken). This introduces bias, questions the relia bility of classifying patients into CSPH 
and severe portal hypertension and for accuracy, a more sensitive measure using cm. 
saline could have been used. The difference of 1 mm, i.e. 11mm (CSPH) and 12 mm 
(severe portal hypertension) will be very difficult  to interpret. When 3 readings were 
obtained, how many times did the investigators have to cancel the prior readings and 
repeat the measurements? How much time was taken for these measurements. Finally, 
and of most concern, how many subjects had no portal hypertension or portal pressure 
<10 mm Hg. and how was that data analyzed?  
 
3. The box and whisker plot figures show significant overlap between the values of the 
stiffness. A scatterplot with mean and standard deviation maybe a better representation.  
 
4. Interpretation and conclusions. Given the modest sensitivity and specificity, the data 
shows that higher values suggest severe portal hypertension while lower liver stiffness 
values do not necessarily exclude severe portal hypertension.  
 
 
5. A few typograp hical errors - need careful review of manuscript for English language. Eg 
page 9, line 17 not "have no", should be "has no" but please review, there are others that 
are not listed here.  
 
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.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
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 asses s the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, consid ering 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, e ither now or in the future?  
 
2. Do yo u hold any stocks or shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, e ither now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the  content of the 
manu script?  
 
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 fin ancial competing interests?  
 
6. Do you have any non -financial c ompeting 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 al ong with the authors' 
responses. 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/ ). I understand that an y comments 
which I do not wish to be included 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