Reviewer’s report
Title: Causative factors of liver fibrosis in HIV-infected patients. A single center study.
Version: 0 Date: 14 May 2019
Reviewer: Jan-Christian Wasmuth
Reviewer's report:
Androutsakos  et  al.  describe  liver  fibrosis  and  possible  risk  factors  as  assessed  by  transient
elastography in a cohort of 188 HIV-infected patients in a cross-sectional design. 173/187 patients were
classified as no / mild fibrosis, 14/187 as significant fibrosis. Several factors were associated with
fibrosis (Age, AST, HCV , Alcohol, CD4/CD8 Ratio).
My main concern is that no data on antiretroviral Treatment are shown. It has been well described in
recent years that control of HIV-infection is a major protective factor for liver fibrosis and ongoing
viral  replication  is  among  the  strongest  risks  for  fibrosis  (among  others:  Hepatology.  2019
Mar;69(3):1135-1150; PLoS One. 2018 Jan 18;13(1):e0191118). On the other hand, especially older
antiretrovirals are known to be associated with fibrosis (and also other Events like non-cirrhotic Portal
Hypertension).  Therefore it is  essential to Show  Basic data  on (at least current)  ART Treatment
(obviously 85% of patients were treated - reasons for the other 15% not?). Additionally CD4/CD8
Ratio in the year 2017 could be a Surrogate of antiviral Treatment.
I wonder how alcohol-use was assessed and defined. As alcohol would be expected to be the most
important co-factor for fibrosis together with Hepatitis cofinfection, the Reader should be able to
understand how this was done.
188 were included, but fibroscan obtained in 187 - why? Due to design it should not be possible to
include a Patient with no fibroscan available.
ROC analysis is used to illustrate the diagnostic ability of a binary classifier system at different
discrimination thresholds. The purpose of the paper is to analyse possibel factors associated with
fibrosis, not to evaluate a diagnostic tool for liver fibrosis.
Do the authors have any follow-up data? As many cross-sectional data have been presented, longer-
term follow-up would be really interesting.
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 the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Unable to assess
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 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 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.
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 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 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: Causative factors of liver fibrosis in HIV-infected patients. A single center study.
Version: 0 Date: 14 May 2019
Reviewer: Jan-Christian Wasmuth
Reviewer's report:
Androutsakos  et  al.  describe  liver  fibrosis  and  possible  risk  factors  as  assessed  by  transient
elastography in a cohort of 188 HIV-infected patients in a cross-sectional design. 173/187 patients were
classified as no / mild fibrosis, 14/187 as significant fibrosis. Several factors were associated with
fibrosis (Age, AST, HCV , Alcohol, CD4/CD8 Ratio).
My main concern is that no data on antiretroviral Treatment are shown. It has been well described in
recent years that control of HIV-infection is a major protective factor for liver fibrosis and ongoing
viral  replication  is  among  the  strongest  risks  for  fibrosis  (among  others:  Hepatology.  2019
Mar;69(3):1135-1150; PLoS One. 2018 Jan 18;13(1):e0191118). On the other hand, especially older
antiretrovirals are known to be associated with fibrosis (and also other Events like non-cirrhotic Portal
Hypertension).  Therefore it is  essential to Show  Basic data  on (at least current)  ART Treatment
(obviously 85% of patients were treated - reasons for the other 15% not?). Additionally CD4/CD8
Ratio in the year 2017 could be a Surrogate of antiviral Treatment.
I wonder how alcohol-use was assessed and defined. As alcohol would be expected to be the most
important co-factor for fibrosis together with Hepatitis cofinfection, the Reader should be able to
understand how this was done.
188 were included, but fibroscan obtained in 187 - why? Due to design it should not be possible to
include a Patient with no fibroscan available.
ROC analysis is used to illustrate the diagnostic ability of a binary classifier system at different
discrimination thresholds. The purpose of the paper is to analyse possibel factors associated with
fibrosis, not to evaluate a diagnostic tool for liver fibrosis.
Do the authors have any follow-up data? As many cross-sectional data have been presented, longer-
term follow-up would be really interesting.
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 the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Unable to assess
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 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 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.
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 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 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: Causative factors of liver fibrosis in HIV-infected patients. A single center study.
Version: 0 Date: 14 May 2019
Reviewer: Jan-Christian Wasmuth
Reviewer's report:
Androutsakos  et  al.  describe  liver  fibrosis  and  possible  risk  factors  as  assessed  by  transient
elastography in a cohort of 188 HIV-infected patients in a cross-sectional design. 173/187 patients were
classified as no / mild fibrosis, 14/187 as significant fibrosis. Several factors were associated with
fibrosis (Age, AST, HCV , Alcohol, CD4/CD8 Ratio).
My main concern is that no data on antiretroviral Treatment are shown. It has been well described in
recent years that control of HIV-infection is a major protective factor for liver fibrosis and ongoing
viral  replication  is  among  the  strongest  risks  for  fibrosis  (among  others:  Hepatology.  2019
Mar;69(3):1135-1150; PLoS One. 2018 Jan 18;13(1):e0191118). On the other hand, especially older
antiretrovirals are known to be associated with fibrosis (and also other Events like non-cirrhotic Portal
Hypertension).  Therefore it is  essential to Show  Basic data  on (at least current)  ART Treatment
(obviously 85% of patients were treated - reasons for the other 15% not?). Additionally CD4/CD8
Ratio in the year 2017 could be a Surrogate of antiviral Treatment.
I wonder how alcohol-use was assessed and defined. As alcohol would be expected to be the most
important co-factor for fibrosis together with Hepatitis cofinfection, the Reader should be able to
understand how this was done.
188 were included, but fibroscan obtained in 187 - why? Due to design it should not be possible to
include a Patient with no fibroscan available.
ROC analysis is used to illustrate the diagnostic ability of a binary classifier system at different
discrimination thresholds. The purpose of the paper is to analyse possibel factors associated with
fibrosis, not to evaluate a diagnostic tool for liver fibrosis.
Do the authors have any follow-up data? As many cross-sectional data have been presented, longer-
term follow-up would be really interesting.
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 the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Unable to assess
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 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 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.
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 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 included as confidential comments
to the editors, which will not be published.
I agree to the open peer review policy of the journal
assistant