Reviewer ’s report  
 
Title:  Title: Predictors of mortality in patients under treatment for chronic Hepatitis B in 
Ethiopia: a prospective cohort study  
 
Version: 0 Date: 17 Jun 2018 
 
Reviewer:  Conrado  Fernandez Rodriguez  
 
Reviewer’s report:  
 
Please include all comments for the authors in this box rather than uploading your report as an 
attachment. Please only upload as attachm ents annotated versions of manuscripts, graphs, 
supporting materials or other aspects of your report which cannot be included in a text format.  
 
Please overwrite this text when adding your comments to the authors.  
 
In this manuscript, the authors report the  effect of antiviral HBV therapy with tenofovir in a 
relatively large Ethiopian HBV infected cohort. The main conclusions were that decompensated 
cirrhosis, older age and low BMI were independent predictors of mortality. On the other hand, 
patients with co mpensated cirrhosis had the same survival rate than those with no cirrhosis, 
emphasizing the importance of early detection and treatment of HBV infected population. This is 
an important piece of information and hopefully this cohort may be followed -up in a  long-term 
basis for generating further new knowledge from a sub -saharan area. I think further clarification 
would help to complete the information contained in the manuscript.  
 
 
Major:  
 
1. It is described that EASL 2012 criteria were applied for treatment e ligibility, however, there 
was >30% of the cohort with baseline DNA -HBV <2,000 IU/ml and >60% with normal or near 
normal ALT. Please clarify this point.  
 
2. Only 276 out of 1303 subjects were finally eligible for treatment. Does it mean that 1,207 did 
not m eet EASL criteria for treatment?  
 
3. Mortality was mostly due to decompensated cirrhosis instead of HCC development. It may 
reflect a relatively short F -U, in this sense, baseline HBV -DNA predicts liver disease progression 
and HCC development, did the model  change if you introduced HBV -DNA in the Cox 
regression analysis?  
 
4. Older age was independently associated with mortality, however advanced liver disease and 
specifically decompensated cirrhosis occur more frequently with longer evolution period. Did 
you explore collinearity between age and decompensated cirrhosis or liver fibrosis stage?  
 
 
Minor:  
 
1. Are newborn or child vaccination included in Regional or National Health programs in 
Ethiopia?  
 
2. You mentioned that written consent was obtained from all part icipants, however the literacy 
rate in Ethiopian adults was 39% in 2007, according to UNESCO data. Please, clarify it.  
 
Are the methods appropriate and well d escribed?  
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.  
 
No 
 
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 competi ng 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 fro m 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, plea se give details below.  
 
I have received fees for lecturing and serving in advisory boards from Gilead Company in the 
past 5 years.  
 
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 uplo ad 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/license s/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:  Title: Predictors of mortality in patients under treatment for chronic Hepatitis B in 
Ethiopia: a prospective cohort study  
 
Version: 0 Date: 17 Jun 2018 
 
Reviewer:  Conrado  Fernandez Rodriguez  
 
Reviewer’s report:  
 
Please include all comments for the authors in this box rather than uploading your report as an 
attachment. Please only upload as attachm ents annotated versions of manuscripts, graphs, 
supporting materials or other aspects of your report which cannot be included in a text format.  
 
Please overwrite this text when adding your comments to the authors.  
 
In this manuscript, the authors report the  effect of antiviral HBV therapy with tenofovir in a 
relatively large Ethiopian HBV infected cohort. The main conclusions were that decompensated 
cirrhosis, older age and low BMI were independent predictors of mortality. On the other hand, 
patients with co mpensated cirrhosis had the same survival rate than those with no cirrhosis, 
emphasizing the importance of early detection and treatment of HBV infected population. This is 
an important piece of information and hopefully this cohort may be followed -up in a  long-term 
basis for generating further new knowledge from a sub -saharan area. I think further clarification 
would help to complete the information contained in the manuscript.  
 
 
Major:  
 
1. It is described that EASL 2012 criteria were applied for treatment e ligibility, however, there 
was >30% of the cohort with baseline DNA -HBV <2,000 IU/ml and >60% with normal or near 
normal ALT. Please clarify this point.  
 
2. Only 276 out of 1303 subjects were finally eligible for treatment. Does it mean that 1,207 did 
not m eet EASL criteria for treatment?  
 
3. Mortality was mostly due to decompensated cirrhosis instead of HCC development. It may 
reflect a relatively short F -U, in this sense, baseline HBV -DNA predicts liver disease progression 
and HCC development, did the model  change if you introduced HBV -DNA in the Cox 
regression analysis?  
 
4. Older age was independently associated with mortality, however advanced liver disease and 
specifically decompensated cirrhosis occur more frequently with longer evolution period. Did 
you explore collinearity between age and decompensated cirrhosis or liver fibrosis stage?  
 
 
Minor:  
 
1. Are newborn or child vaccination included in Regional or National Health programs in 
Ethiopia?  
 
2. You mentioned that written consent was obtained from all part icipants, however the literacy 
rate in Ethiopian adults was 39% in 2007, according to UNESCO data. Please, clarify it.  
 
Are the methods appropriate and well d escribed?  
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.  
 
No 
 
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 competi ng 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 fro m 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, plea se give details below.  
 
I have received fees for lecturing and serving in advisory boards from Gilead Company in the 
past 5 years.  
 
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 uplo ad 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/license s/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:  Title: Predictors of mortality in patients under treatment for chronic Hepatitis B in 
Ethiopia: a prospective cohort study  
 
Version: 0 Date: 17 Jun 2018 
 
Reviewer:  Conrado  Fernandez Rodriguez  
 
Reviewer’s report:  
 
Please include all comments for the authors in this box rather than uploading your report as an 
attachment. Please only upload as attachm ents annotated versions of manuscripts, graphs, 
supporting materials or other aspects of your report which cannot be included in a text format.  
 
Please overwrite this text when adding your comments to the authors.  
 
In this manuscript, the authors report the  effect of antiviral HBV therapy with tenofovir in a 
relatively large Ethiopian HBV infected cohort. The main conclusions were that decompensated 
cirrhosis, older age and low BMI were independent predictors of mortality. On the other hand, 
patients with co mpensated cirrhosis had the same survival rate than those with no cirrhosis, 
emphasizing the importance of early detection and treatment of HBV infected population. This is 
an important piece of information and hopefully this cohort may be followed -up in a  long-term 
basis for generating further new knowledge from a sub -saharan area. I think further clarification 
would help to complete the information contained in the manuscript.  
 
 
Major:  
 
1. It is described that EASL 2012 criteria were applied for treatment e ligibility, however, there 
was >30% of the cohort with baseline DNA -HBV <2,000 IU/ml and >60% with normal or near 
normal ALT. Please clarify this point.  
 
2. Only 276 out of 1303 subjects were finally eligible for treatment. Does it mean that 1,207 did 
not m eet EASL criteria for treatment?  
 
3. Mortality was mostly due to decompensated cirrhosis instead of HCC development. It may 
reflect a relatively short F -U, in this sense, baseline HBV -DNA predicts liver disease progression 
and HCC development, did the model  change if you introduced HBV -DNA in the Cox 
regression analysis?  
 
4. Older age was independently associated with mortality, however advanced liver disease and 
specifically decompensated cirrhosis occur more frequently with longer evolution period. Did 
you explore collinearity between age and decompensated cirrhosis or liver fibrosis stage?  
 
 
Minor:  
 
1. Are newborn or child vaccination included in Regional or National Health programs in 
Ethiopia?  
 
2. You mentioned that written consent was obtained from all part icipants, however the literacy 
rate in Ethiopian adults was 39% in 2007, according to UNESCO data. Please, clarify it.  
 
Are the methods appropriate and well d escribed?  
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.  
 
No 
 
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 competi ng 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 fro m 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, plea se give details below.  
 
I have received fees for lecturing and serving in advisory boards from Gilead Company in the 
past 5 years.  
 
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 uplo ad 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/license s/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