Reviewer ’s report  
 
Title: Ultrasonic Assessment of Liver Stiffness and Carotid Art ery Elasticity in Patients with 
Chronic Viral Hepatitis  
 
Version: 2 Date: 06 Jun 2018  
 
Reviewer: Robert Akins  
 
Reviewer's report:  
 
The study investigated associations between hepatic tissue stiffness and elastic parameters 
measured in carotid artery. Statistically significant differences in arterial elasticity were found 
even though the intimal -medial thicknesses across groups were si milar. The results suggest 
functional/structural changes in arteries associated with hepatitis B/C and liver fibrosis.  I found 
the study interesting, but there are some clarifications and corrections required.  
 
 
In Abstract:  
In the conclusion section, the  phrase, "their functional elasticity parameters had already changed" 
implies a temporal relationship that was not evaluated. The observation that differences  in 
elasticity were seen in the absence of differences in IMT is interesting and should be better  
highlighted.  Similar wording in the discussion should also be replaced.  
 
 
In Introduction  
The final sentence, "These findings would help to determine whether the degree of liver fibrosis 
is related to macrovascular diseases" is not well -supported by the  data provided. The study 
associated liver fibrosis with carotid artery properties, but the relationship between the two was 
not evaluated. Please reword accordingly.  
 
 
In Methods:  
1) Under 2.2 Quantitative Measurement ..., define how the "region for measurement" was 
identified or selected.  
 
2) Under 2.3 Clinical Information #1, indicate all "laboratory indicators" that were evaluated and 
how they were acquired. For example: Were blo od values collected from patients medical 
records? Were they from venous blood? When were they acquired at the time of the liver and 
vascular measures? Etc.  
 
3) Under 2.3 Clinical Information #2, please indicate all "other indicators" and how they were 
acquired. For example: Were blood pressures taken from brachial artery at the time of the 
ultrasound assessments? Etc.  
 
4) Under 3.0 Statistical Analysis, please clarify the post hoc test used. The text indicates that t 
tests were employed after ANOVA (with Levene's test to verify homogenous variance); were 
these Bonferroni corrected? If comparisons are between each test group (CHB and CHC) 
separately to control, a Dunnett test should be considered.  
 
 
In Results:  
1) In section 2, last paragraph (~line numbers  12 - 17), the order of the alpha values is not clear; 
the groups are listed CHC, CHB, control, but the values (3.03, 4.13, 5.77) don't seem tp match 
this order.  
 
 
 
In Discussion:  
 
1) The statement, "... patients with viral hepatitis suffer a higher risk of cardiovascular 
events ..." is not supported by the data in the paper, which did not assess risk. Increased 
carotid stiffness in CHC only suggests those patients are at higher risk.  
 
 
2) A discussion of possible mechanisms by which carotid stiffness might be  increased in the 
absence of significantly elevated blood pressure and with normal levels of biomarkers for 
atherosclerosis. For example, is there a linkage with altered elastin/collagen distribution 
associated with infection?  
 
 
Figures:  
 
The Y axis in fig ure 3 is mislabeled. Please correct.  
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported b y the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specif y 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, f ees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publi cation of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat 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 curr ently 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 have no competing interests.  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named re port 
including any attachments I upload will be posted on the website along 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 underst and that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editor s, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Ultrasonic Assessment of Liver Stiffness and Carotid Art ery Elasticity in Patients with 
Chronic Viral Hepatitis  
 
Version: 2 Date: 06 Jun 2018  
 
Reviewer: Robert Akins  
 
Reviewer's report:  
 
The study investigated associations between hepatic tissue stiffness and elastic parameters 
measured in carotid artery. Statistically significant differences in arterial elasticity were found 
even though the intimal -medial thicknesses across groups were si milar. The results suggest 
functional/structural changes in arteries associated with hepatitis B/C and liver fibrosis.  I found 
the study interesting, but there are some clarifications and corrections required.  
 
 
In Abstract:  
In the conclusion section, the  phrase, "their functional elasticity parameters had already changed" 
implies a temporal relationship that was not evaluated. The observation that differences  in 
elasticity were seen in the absence of differences in IMT is interesting and should be better  
highlighted.  Similar wording in the discussion should also be replaced.  
 
 
In Introduction  
The final sentence, "These findings would help to determine whether the degree of liver fibrosis 
is related to macrovascular diseases" is not well -supported by the  data provided. The study 
associated liver fibrosis with carotid artery properties, but the relationship between the two was 
not evaluated. Please reword accordingly.  
 
 
In Methods:  
1) Under 2.2 Quantitative Measurement ..., define how the "region for measurement" was 
identified or selected.  
 
2) Under 2.3 Clinical Information #1, indicate all "laboratory indicators" that were evaluated and 
how they were acquired. For example: Were blo od values collected from patients medical 
records? Were they from venous blood? When were they acquired at the time of the liver and 
vascular measures? Etc.  
 
3) Under 2.3 Clinical Information #2, please indicate all "other indicators" and how they were 
acquired. For example: Were blood pressures taken from brachial artery at the time of the 
ultrasound assessments? Etc.  
 
4) Under 3.0 Statistical Analysis, please clarify the post hoc test used. The text indicates that t 
tests were employed after ANOVA (with Levene's test to verify homogenous variance); were 
these Bonferroni corrected? If comparisons are between each test group (CHB and CHC) 
separately to control, a Dunnett test should be considered.  
 
 
In Results:  
1) In section 2, last paragraph (~line numbers  12 - 17), the order of the alpha values is not clear; 
the groups are listed CHC, CHB, control, but the values (3.03, 4.13, 5.77) don't seem tp match 
this order.  
 
 
 
In Discussion:  
 
1) The statement, "... patients with viral hepatitis suffer a higher risk of cardiovascular 
events ..." is not supported by the data in the paper, which did not assess risk. Increased 
carotid stiffness in CHC only suggests those patients are at higher risk.  
 
 
2) A discussion of possible mechanisms by which carotid stiffness might be  increased in the 
absence of significantly elevated blood pressure and with normal levels of biomarkers for 
atherosclerosis. For example, is there a linkage with altered elastin/collagen distribution 
associated with infection?  
 
 
Figures:  
 
The Y axis in fig ure 3 is mislabeled. Please correct.  
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported b y the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specif y 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, f ees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publi cation of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat 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 curr ently 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 have no competing interests.  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named re port 
including any attachments I upload will be posted on the website along 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 underst and that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editor s, 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: Ultrasonic Assessment of Liver Stiffness and Carotid Art ery Elasticity in Patients with 
Chronic Viral Hepatitis  
 
Version: 2 Date: 06 Jun 2018  
 
Reviewer: Robert Akins  
 
Reviewer's report:  
 
The study investigated associations between hepatic tissue stiffness and elastic parameters 
measured in carotid artery. Statistically significant differences in arterial elasticity were found 
even though the intimal -medial thicknesses across groups were si milar. The results suggest 
functional/structural changes in arteries associated with hepatitis B/C and liver fibrosis.  I found 
the study interesting, but there are some clarifications and corrections required.  
 
 
In Abstract:  
In the conclusion section, the  phrase, "their functional elasticity parameters had already changed" 
implies a temporal relationship that was not evaluated. The observation that differences  in 
elasticity were seen in the absence of differences in IMT is interesting and should be better  
highlighted.  Similar wording in the discussion should also be replaced.  
 
 
In Introduction  
The final sentence, "These findings would help to determine whether the degree of liver fibrosis 
is related to macrovascular diseases" is not well -supported by the  data provided. The study 
associated liver fibrosis with carotid artery properties, but the relationship between the two was 
not evaluated. Please reword accordingly.  
 
 
In Methods:  
1) Under 2.2 Quantitative Measurement ..., define how the "region for measurement" was 
identified or selected.  
 
2) Under 2.3 Clinical Information #1, indicate all "laboratory indicators" that were evaluated and 
how they were acquired. For example: Were blo od values collected from patients medical 
records? Were they from venous blood? When were they acquired at the time of the liver and 
vascular measures? Etc.  
 
3) Under 2.3 Clinical Information #2, please indicate all "other indicators" and how they were 
acquired. For example: Were blood pressures taken from brachial artery at the time of the 
ultrasound assessments? Etc.  
 
4) Under 3.0 Statistical Analysis, please clarify the post hoc test used. The text indicates that t 
tests were employed after ANOVA (with Levene's test to verify homogenous variance); were 
these Bonferroni corrected? If comparisons are between each test group (CHB and CHC) 
separately to control, a Dunnett test should be considered.  
 
 
In Results:  
1) In section 2, last paragraph (~line numbers  12 - 17), the order of the alpha values is not clear; 
the groups are listed CHC, CHB, control, but the values (3.03, 4.13, 5.77) don't seem tp match 
this order.  
 
 
 
In Discussion:  
 
1) The statement, "... patients with viral hepatitis suffer a higher risk of cardiovascular 
events ..." is not supported by the data in the paper, which did not assess risk. Increased 
carotid stiffness in CHC only suggests those patients are at higher risk.  
 
 
2) A discussion of possible mechanisms by which carotid stiffness might be  increased in the 
absence of significantly elevated blood pressure and with normal levels of biomarkers for 
atherosclerosis. For example, is there a linkage with altered elastin/collagen distribution 
associated with infection?  
 
 
Figures:  
 
The Y axis in fig ure 3 is mislabeled. Please correct.  
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported b y the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specif y 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, f ees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publi cation of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat 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 curr ently 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 have no competing interests.  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named re port 
including any attachments I upload will be posted on the website along 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 underst and that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editor s, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant