Reviewer ’s report  
 
Title: Liver fibrosis and accelerated immune dysfunction (immu nosenescence) among 
HIVinfected Russians with heavy alcohol consumption - An ob servational cross -sectional 
study  
 
Version: 0 Date: 16 Feb 2019  
 
Reviewer: Zhou Zhou  
 
Reviewer's report:  
 
The current study analyzes the heavy alcohol drinking on immune cell senescence in Russian 
HIV patients and the potenti al relationship on liver fibrosis. Here are some major concerns:  
 
1. Fibrosis is a long -term pathological process. In this report some risk factors are 
analyzed. However, how long time of exposure of these factors are not sure. The 
authors need to determine  some of the crucial long -term risk factors and determine 
whether they may really contribute to fibrosis. The years of HBV/HCV infection, 
years of steatosis, years of heavy drinking, years of smoking, and years of overweight 
are some parameters to be bette r defined. If the authors make analysis on short term 
effects on the immune system according to the fibrosis level, the results may well be 
negative. However, it may not accurately present the relationship of the analyzed 
terms.  
 
2. The authors say the adva nced fibrotic group has higher HIV RNA replication. 
However, it does not show in Table 1.  
 
3. What are the numbers in Table 2 and 3? Are these flow cytometry result percentage of 
a group? If so, the authors need to show the flow cytometry strategy and defin e the 
percentage of which group is shown. If the results are the cell concentration, the 
authors need to put unit into all the results. In the current study, the cell concentration 
is needed for calculation.  
 
4. The authors need to provide better descriptio n how Table 4, 5 and 6 is calculated. As 
described in the method section, the slope is calculated according to multiple linear 
regression and then the authors showed the advanced fibrotic/non -fibrotic ratio. If this 
is the case, the authors need to present  the original slope for all the categories for each 
group, instead of a simple ratio. Also, for many parameters, including sex, whether 
fibrosis is advanced, whether the patients are currently smoking, whether the patients 
have hepatitis, there is no conti nuous base for regression, while others such as age, 
years of HIV diagnosis or HIV copy, actually have the continuous base for regression. 
How can the authors put the data together to make one regression analysis? Did the 
author actually work on some regre ssion analysis and some others simply to 
categorize the data with other analysis?  
 
5. If the authors analyzed the data through multiple linear regression, have the authors 
analyzed interaction effect between different factors?  
 
6. The authors used one catego ry for continuous regression in Table 6. To make the 
work complete, a similar analysis on memory T cell/naïve T cell as well as CD4+ T 
cells should be presented.  
 
7. The authors should discuss the reason and indication that the results in the current 
study are negative regarding the effect of HIV infection.  
 
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 by 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 sta tistical review?  
If an additional statistical review is recommended, please speci fy 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 langua ge 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 financial ly from 
the publication 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 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 f or 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 understan d that my name will be 
included on my report to the authors and, if the manuscript is accepted f or publication, my 
named report 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 understand that 
any comments which I do not wish to be included in my named report can be in cluded as 
confidential comments to the editors, which will not be published.  
 
I agree to the open pee r review policy of the journal  
Reviewer ’s report  
 
Title: Liver fibrosis and accelerated immune dysfunction (immu nosenescence) among 
HIVinfected Russians with heavy alcohol consumption - An ob servational cross -sectional 
study  
 
Version: 0 Date: 16 Feb 2019  
 
Reviewer: Zhou Zhou  
 
Reviewer's report:  
 
The current study analyzes the heavy alcohol drinking on immune cell senescence in Russian 
HIV patients and the potenti al relationship on liver fibrosis. Here are some major concerns:  
 
1. Fibrosis is a long -term pathological process. In this report some risk factors are 
analyzed. However, how long time of exposure of these factors are not sure. The 
authors need to determine  some of the crucial long -term risk factors and determine 
whether they may really contribute to fibrosis. The years of HBV/HCV infection, 
years of steatosis, years of heavy drinking, years of smoking, and years of overweight 
are some parameters to be bette r defined. If the authors make analysis on short term 
effects on the immune system according to the fibrosis level, the results may well be 
negative. However, it may not accurately present the relationship of the analyzed 
terms.  
 
2. The authors say the adva nced fibrotic group has higher HIV RNA replication. 
However, it does not show in Table 1.  
 
3. What are the numbers in Table 2 and 3? Are these flow cytometry result percentage of 
a group? If so, the authors need to show the flow cytometry strategy and defin e the 
percentage of which group is shown. If the results are the cell concentration, the 
authors need to put unit into all the results. In the current study, the cell concentration 
is needed for calculation.  
 
4. The authors need to provide better descriptio n how Table 4, 5 and 6 is calculated. As 
described in the method section, the slope is calculated according to multiple linear 
regression and then the authors showed the advanced fibrotic/non -fibrotic ratio. If this 
is the case, the authors need to present  the original slope for all the categories for each 
group, instead of a simple ratio. Also, for many parameters, including sex, whether 
fibrosis is advanced, whether the patients are currently smoking, whether the patients 
have hepatitis, there is no conti nuous base for regression, while others such as age, 
years of HIV diagnosis or HIV copy, actually have the continuous base for regression. 
How can the authors put the data together to make one regression analysis? Did the 
author actually work on some regre ssion analysis and some others simply to 
categorize the data with other analysis?  
 
5. If the authors analyzed the data through multiple linear regression, have the authors 
analyzed interaction effect between different factors?  
 
6. The authors used one catego ry for continuous regression in Table 6. To make the 
work complete, a similar analysis on memory T cell/naïve T cell as well as CD4+ T 
cells should be presented.  
 
7. The authors should discuss the reason and indication that the results in the current 
study are negative regarding the effect of HIV infection.  
 
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 by 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 sta tistical review?  
If an additional statistical review is recommended, please speci fy 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 langua ge 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 financial ly from 
the publication 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 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 f or 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 understan d that my name will be 
included on my report to the authors and, if the manuscript is accepted f or publication, my 
named report 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 understand that 
any comments which I do not wish to be included in my named report can be in cluded as 
confidential comments to the editors, which will not be published.  
 
I agree to the open pee r review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Liver fibrosis and accelerated immune dysfunction (immu nosenescence) among 
HIVinfected Russians with heavy alcohol consumption - An ob servational cross -sectional 
study  
 
Version: 0 Date: 16 Feb 2019  
 
Reviewer: Zhou Zhou  
 
Reviewer's report:  
 
The current study analyzes the heavy alcohol drinking on immune cell senescence in Russian 
HIV patients and the potenti al relationship on liver fibrosis. Here are some major concerns:  
 
1. Fibrosis is a long -term pathological process. In this report some risk factors are 
analyzed. However, how long time of exposure of these factors are not sure. The 
authors need to determine  some of the crucial long -term risk factors and determine 
whether they may really contribute to fibrosis. The years of HBV/HCV infection, 
years of steatosis, years of heavy drinking, years of smoking, and years of overweight 
are some parameters to be bette r defined. If the authors make analysis on short term 
effects on the immune system according to the fibrosis level, the results may well be 
negative. However, it may not accurately present the relationship of the analyzed 
terms.  
 
2. The authors say the adva nced fibrotic group has higher HIV RNA replication. 
However, it does not show in Table 1.  
 
3. What are the numbers in Table 2 and 3? Are these flow cytometry result percentage of 
a group? If so, the authors need to show the flow cytometry strategy and defin e the 
percentage of which group is shown. If the results are the cell concentration, the 
authors need to put unit into all the results. In the current study, the cell concentration 
is needed for calculation.  
 
4. The authors need to provide better descriptio n how Table 4, 5 and 6 is calculated. As 
described in the method section, the slope is calculated according to multiple linear 
regression and then the authors showed the advanced fibrotic/non -fibrotic ratio. If this 
is the case, the authors need to present  the original slope for all the categories for each 
group, instead of a simple ratio. Also, for many parameters, including sex, whether 
fibrosis is advanced, whether the patients are currently smoking, whether the patients 
have hepatitis, there is no conti nuous base for regression, while others such as age, 
years of HIV diagnosis or HIV copy, actually have the continuous base for regression. 
How can the authors put the data together to make one regression analysis? Did the 
author actually work on some regre ssion analysis and some others simply to 
categorize the data with other analysis?  
 
5. If the authors analyzed the data through multiple linear regression, have the authors 
analyzed interaction effect between different factors?  
 
6. The authors used one catego ry for continuous regression in Table 6. To make the 
work complete, a similar analysis on memory T cell/naïve T cell as well as CD4+ T 
cells should be presented.  
 
7. The authors should discuss the reason and indication that the results in the current 
study are negative regarding the effect of HIV infection.  
 
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 by 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 sta tistical review?  
If an additional statistical review is recommended, please speci fy 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 langua ge 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 financial ly from 
the publication 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 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 f or 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 understan d that my name will be 
included on my report to the authors and, if the manuscript is accepted f or publication, my 
named report 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 understand that 
any comments which I do not wish to be included in my named report can be in cluded as 
confidential comments to the editors, which will not be published.  
 
I agree to the open pee r review policy of the journal  
assistant